Policy Review

Management of multiple myeloma-related renal

impairment: recommendations from the International
Myeloma Working Group
Meletios A Dimopoulos, Giampaolo Merlini, Frank Bridoux, Nelson Leung, Joseph Mikhael, Simon J Harrison, Efstathios Kastritis, Laurent Garderet,
Alessandro Gozzetti, Niels W C J van de Donk, Katja C Weisel, Ashraf Z Badros, Meral Beksac, Jens Hillengass, Mohamad Mohty, P Joy Ho,
Ioannis Ntanasis-Stathopoulos, Maria-Victoria Mateos, Paul Richardson, Joan Blade, Philippe Moreau, Jesus San-Miguel, Nikhil Munshi,
S Vincent Rajkumar, Brian G M Durie, Heinz Ludwig, Evangelos Terpos, on behalf of the International Myeloma Working Group*

Here, the International Myeloma Working Group (IMWG) updates its clinical practice recommendations for the Lancet Oncol 2023; 24: e293–311
management of multiple myeloma-related renal impairment on the basis of data published until Dec 31, 2022. All *Members listed in the appendix
patients with multiple myeloma and renal impairment should have serum creatinine, estimated glomerular filtration (pp 2–13)
rate, and free light chains (FLCs) measurements together with 24-h urine total protein, electrophoresis, and Department of Clinical
Therapeutics, School of
immunofixation. If non-selective proteinuria (mainly albuminuria) or involved serum FLCs value less than 500 mg/L
Medicine, National and
is detected, then a renal biopsy is needed. The IMWG criteria for the definition of renal response should be used. Kapodistrian University of
Supportive care and high-dose dexamethasone are required for all patients with myeloma-induced renal impairment. Athens, Alexandra General
Mechanical approaches do not increase overall survival. Bortezomib-based regimens are the cornerstone of the Hospital, Athens, Greece
(Prof M A Dimopoulos MD,
management of patients with multiple myeloma and renal impairment at diagnosis. New quadruplet and triplet
Prof E Kastritis MD,
combinations, including proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies, I Ntanasis-Stathopoulos MD,
improve renal and survival outcomes in both newly diagnosed patients and those with relapsed or refractory disease. Prof E Terpos MD); Amyloidosis
Conjugated antibodies, chimeric antigen receptor T-cells, and T-cell engagers are well tolerated and effective in Research and Treatment
Center, IRCCS Policlinico
patients with moderate renal impairment.
San Matteo and University of
Pavia, Pavia, Italy
Introduction The introduction of new agents against multiple (Prof G Merlini MD);
Renal impairment is among the cardinal features of myeloma has enhanced the therapeutic choices for Department of Nephrology,
Centre Hospitalier
multiple myeloma; up to 50% of patients with multiple patients with multiple myeloma both at diagnosis and at
Universitaire, Université de
myeloma present with renal impairment (defined as relapsed or refractory disease.16 However, special Poitiers, Poitiers, France
estimated glomerular filtration rate [eGFR] <60 mL/min considerations have to be made for patients with renal (Prof F Bridoux MD);
per 1·73 m²) at the time of diagnosis, and 2–4% require impairment. The International Myeloma Working Nephrology and Hypertension,
Department of Medicine
dialysis.1–5 The differences in the reported incidence of Group (IMWG) aimed to review all currently available (Prof N Leung MD) and Division
renal impairment among studies might be partly evidence and update previous recommendations17 for the of Hematology
attributed to different definitions of renal impairment, management of renal impairment in patients with (Prof S V Rajkumar MD), Mayo
including serum creatinine concentrations higher than multiple myeloma. Clinic, Rochester, MN, USA;
Translational Genomics
2 mg/dL or higher than the upper normal limit,2,5 and Research Institute, City of Hope
eGFR less than 60 mL/min per 1·73 m²,1 or less than Methods Cancer Center, Phoenix, AZ,
40 mL/min per 1·73 m².2,6 Search strategy and selection criteria USA (Prof J Mikhael MD);
Renal impairment has been linked to decreased overall An interdisciplinary panel of clinical experts on multiple Peter MacCallum Cancer
Centre, Royal Melbourne
survival and increased risk of early death for people with myeloma and renal impairment reviewed available Hospital, Melbourne, VIC,
multiple myeloma.2,5,7–10 A meta-analysis of 11 randomised evidence published in randomised clinical studies, meta- Australia (Prof S J Harrison PhD);
controlled trials done between 2005 and 2019 found that analyses, systematic reviews of published clinical studies, Sir Peter MacCallum
patients with multiple myeloma and renal impairment observational studies, and case reports, and developed Department of Oncology,
University of Melbourne,
had a greater relative risk of myeloma progression or these recommendations on behalf of the IMWG. The Melbourne, VIC, Australia
mortality than those without renal impairment, for panel included myeloma and nephrologist specialists (Prof S J Harrison); Service
both newly diagnosed patients (relative risk 1·07, who are members of the IMWG. The recommendations d’Hématologie, Hopital Pitié
95% CI 1·001–1·046; p=0·05) and patients with relapsed were initially circulated in draft form to each panel Salpetriere, Paris, France
(L Garderet MD); Department of
or refractory disease (1·20, 1·003–1·431; p=0·05).11 member, who had an opportunity to comment on the Hematology, University of
New therapies, such as proteasome inhibitors, immuno- levels of evidence as well as the systematic grading of Siena, Policlinico S Maria alle
modulatory drugs, and monoclonal antibodies, improved clinical data supporting each recommendation. The Scotte, Siena, Italy
(A Gozzetti MD); Department of
both overall survival and kidney function, especially when manuscript subsequently underwent rounds of revision
Hematology, Amsterdam UMC,
compared with standard chemotherapy.7,8,12–15 Despite the until consensus was reached by all authors. MEDLINE, Vrije Universiteit Amsterdam,
fact that improved renal function has been associated Embase, and Cochrane bibliographic databases, along Amsterdam, Netherlands
with prolonged survival, overall survival was still lower in with abstract lists from major haematology–oncology (Prof N W C J van de Donk MD);
University Medical Center
patients presenting with renal impairment than patients conferences including the American Society of
Hamburg-Eppendorf,
without renal impairment at the time of multiple Hematology, the American Society of Clinical Oncology, Hamburg, Germany
myeloma diagnosis.5,7,8 the European Hematology Association, and the European (Prof K C Weisel MD);

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Department of Medicine, Society for Medical Oncology were searched from deposition disease, light-chain proximal tubulopathy,
University of Maryland conception to Dec 31, 2022, for studies written in English, Fanconi syndrome, cryoglobulinaemic glomerulonephritis
Marlene and
French, German, or Spanish. Search terms included (type I and II), proliferative glomerulonephritis with
Stewart Greenebaum
Comprehensive Cancer Center, a combination of the following: “multiple myeloma”, monoclonal immunoglobulin deposits, cryocrystalglobu-
University of Maryland School “myeloma”, “creatinine clearance”, “eGFR”, “renal”, linaemia or crystalglobulin-induced nephropathy, crystal-
of Medicine, Baltimore, MD, “renal impairment”, “renal dysfunction”, “renal storing histiocytosis, immunotactoid glomerulonephritis,
USA (Prof A Z Badros MD);
Department of Hematology,
insufficiency”, “renal response”, “acute kidney injury”, and C3 glomerulopathy with monoclonal gammopathy.21
Ankara University School of “chronic kidney disease”, “cast nephropathy”, “dialysis”, The presence of at least one of these entities associated
Medicine, Ankara, Turkey “plasmapheresis”, and “renal biopsy”. with the production of nephrotoxic monoclonal
(Prof M Beksac MD); Roswell immunoglobulin in the absence of otherwise symptomatic
Park Comprehensive Cancer
Center, Buffalo, NY, USA
Levels of evidence, grade recommendations, and multiple myeloma lies in the spectrum of monoclonal
(Prof J Hillengass MD); consensus formation gammopathy of renal significance.21,22
Department of Hematology, Levels of evidence and grades of recommendations were Non-immunoglobulin related factors could also lead to
Hôpital Saint-Antoine, assigned using established criteria in line with the Grading renal impairment in patients with multiple myeloma,
Sorbonne University and
INSERM UMRs 938, Paris,
of Recommendations, Assessment, Development, and including dehydration, hypercalcaemia, infections,
France (Prof M Mohty MD); Evaluation (GRADE) system and in accordance with the tumour lysis syndrome, nephrotoxic drugs, such as non-
Institute of Haematology, previously published recommendations from the IMWG steroidal anti-inflammatory drugs, contrast media,
Royal Prince Alfred Hospital, (appendix p 1).18,19 When published clinical data were antibiotics, diuretics, and renin–angiotensin–aldosterone
University of Sydney, Sydney,
NSW, Australia
deemed insufficient to make clear conclusions, an expert system blockers, and anti-myeloma treatment, including
(Prof P J Ho MD); Hospital panel consensus provided further recommendations. We bisphosphonates and possibly carfilzomib.17,20 Taking into
Universitario de Salamanca, did not receive any external support. The first draft was consideration that the median age at multiple myeloma
Salamanca, Spain
distributed to each panel member for critical review and diagnosis is approximately 70 years,23 normal age-related
(M-V Mateos MD); Dana-Farber
Cancer Institute, Harvard input. The paper was revised three times by the panel decline in renal function and the presence of
Medical School, Boston, MA, members before reaching consensus by all authors and comorbidities, such as diabetes, atherosclerotic vascular
USA (Prof P Richardson MD, formulating the final recommendations. Compared with disease, and heart failure, might predispose for renal
Prof N Munshi MD);
the recommendations on diagnosis and staging, the main impairment in these patients.
Department of Hematology,
Hospital Clinic, IDIBAPS, updates of the current recommendations pertain to the
Barcelona, Spain (J Blade MD); therapeutic approach to multiple myeloma-related renal Diagnosis and staging of renal impairment in
Department of Hematology, impairment. patients with multiple myeloma
University Hospital of Nantes,
Early identification and prompt management of
Nantes, France
(Prof P Moreau MD); Cancer Pathophysiology of renal impairment in renal impairment both at diagnosis and at relapse is
Center Clinica Universidad de patients with multiple myeloma of utmost importance to optimise patient outcomes.24
Navarra, CCUN, Centro de Renal damage in patients with multiple myeloma is The IMWG defines renal impairment in people with
Investigación Médica Aplicada,
primarily attributed to the toxic effects of monoclonal free multiple myeloma as serum creatinine higher than
Instituto de Investigación
Sanitaria de Navarra, Centro de light chains (FLCs) on the glomeruli and renal tubules.17,20 2 mg/dL (170 μmol/L) or impaired creatinine clearance
Investigación Biomédica en Under physiological conditions, FLCs are freely filtered (<40 mL/min) due to multiple myeloma.6,17 An
Red Cáncer, Pamplona, Spain through the glomerulus, endocytosed by proximal tubule algorithmic approach should be followed to differentiate
(Prof J San-Miguel MD);
cells through the megalin–cubulin receptor complex, and between the potential causes of renal impairment in
Department of Hematology/
Oncology, Cedars-Sinai Medical catabolised. In patients with multiple myeloma, the patients with multiple myeloma (figure). More than one
Center, Los Angeles, CA, USA overproduction of monoclonal FLCs can surpass the immunoglobulin-related or immunoglobulin-unrelated
(Prof B G M Durie MD); absorptive and catabolic capacity of proximal tubule cells.20 kidney disease might be present in the same patient
Wilhelminen Cancer Research
Institute, First Department of
Residual FLCs in the proximal tubules might activate concomitantly. The pattern of 24-h urine protein
Medicine, Clinic Ottakring, apoptotic molecular cascades and induce inflammation, electrophoresis and serum FLC concentrations might
Vienna, Austria which leads to fibrosis. Unabsorbed FLCs that reach the lead to the diagnosis.25,26 Renal biopsy might be required
(Prof H Ludwig MD) distal nephron can interact with Tamm-Horsfall protein for patients with inconclusive results (figure). Therefore,
Correspondence to: and form aggregates, which precipitate and result in cast collaboration with the nephrologist should be promptly
Prof Evangelos Terpos,
formation and subsequent tubular obstruction and initiated for diagnostic evaluation and treatment.
Department of Clinical
Therapeutics, School of inflammation.20 These are the main pathophysiological The eGFR could be calculated with the Chronic
Medicine, National and mechanisms that lead to light-chain cast nephropathy, Kidney Disease Epidemiology Collaboration (CKD-EPI)27,28
Kapodistrian University of which is found in most patients with multiple myeloma equation without the race variable,29 to measure creatinine
Athens, Alexandra General
Hospital, Athens 11528, Greece
and might lead to acute kidney injury.21 When light-chain clearance in patients with stable renal function.30 The
eterpos@med.uoa.gr cast nephropathy occurs in the setting of a plasma cell CKD classification can be used for the staging of stable
See Online for appendix disorder, it is called myeloma cast nephropathy. renal impairment (table 1).31 The addition of cystatin C in
Other renal diseases that might co-exist and are associated the CKD-EPI equation outperforms the Modification of
with the deposition or precipitation of the entire monoclonal Diet in Renal Disease formula,32 in terms of both
immunoglobulin or its fragments include immunoglobulin- sensitivity for renal impairment detection and prognostic
related amyloidosis, monoclonal immunoglobulin value for overall survival in newly diagnosed patients with

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At diagnosis:
• Serum creatinine, urea, sodium, potassium, calcium, and eGFR (CKD-EPI)
• Total protein, electrophoresis, and immunofixation of a sample from a 24-h urine collection
• Serum FLCs

• Selective proteinuria, light chains predominate • Non-selective proteinuria or substantial • No proteinuria

• High serum FLCs (≥500 mg/L) albuminuria
• Low serum FLCs (<500 mg/L)

Myeloma cast nephropathy Glomerular or tubular pathology Consider alternative diagnosis for renal
A kidney biopsy is probably not necessary but • AL amyloidosis or impairment
might be helpful in patients with comorbidities • Monoclonal immunoglobulin deposition • Kidney biopsy
(diabetes, hypertension, etc) disease or
• Other condition related or unrelated to
monoclonal immunoglobulin
• If clinical suspicion of amyloidosis, proceed with
subcutaneous fat biopsy (Congo red-positive)
• If Congo red-negative, kidney biopsy is often
necessary

Figure: Algorithm for the differential diagnosis of renal impairment in patients with multiple myeloma
CKD-EPI=Chronic Kidney Disease Epidemiology Collaboration. eGFR=estimated glomerular filtration rate. FLCs=free light chains.

multiple myeloma.33,34 The National Kidney Foundation

Description eGFR (mL/min
and the American Society of Nephrology Task Force per 1·73m²)
recommend national efforts to facilitate increased,
1 Normal or elevated eGFR ≥90
routine, and timely use of cystatin C, especially to confirm
eGFR in adults who are at risk for or have chronic kidney 2 Mild reduction in eGFR 60–89
disease, because combining filtration markers (creatinine 3 Moderate reduction in eGFR 30–59
and cystatin C) is more accurate and would support better 4 Severe reduction in eGFR 15–29
clinical decisions than either marker alone.29 However, 5 Renal failure or end-stage renal disease <15 or RRT
continuous refinement of the equation to estimate GFR is
eGFR=estimated glomerular filtration rate. RRT=renal replacement therapy
still ongoing.35 Furthermore, β2-microglobulin concen-
trations are increased in patients with multiple myeloma Table 1: Staging of chronic kidney disease
and renal impairment and this parameter is included in
the revised International Staging System for multiple
myeloma.36 The differential prognostic impact of increased a 24-h urine collection at diagnosis and at disease
β2-microglobulin concentrations from tumour load assessment (grade A recommendation). If non-selective
versus renal impairment is not known. proteinuria (mainly albuminuria) or involved serum FLCs
In cases of acute kidney injury, the Kidney Disease: value less than 500 mg/L is detected, and in the absence of
Improving Global Outcomes (KDIGO), the Risk, Injury, other known causes of exacerbation of renal impairment,
Failure, Loss, and End-stage kidney disease (RIFLE), and such as nephrotoxic medications, hypercalcaemia,
the Acute Kidney Injury Network (AKIN) criteria can infection, and dehydration, then a renal biopsy should be
be used (table 2).37 KDIGO and AKIN might be more done to identify the cause of renal impairment, especially
sensitive for the detection of acute kidney injury in in the absence of amyloid material in subcutaneous fat or
critically ill patients.37 However, RIFLE might identify in other tissues (grade B recommendation).
more patients with haematological malignancies and The CKD-EPI formula without the race variable should
acute kidney injury after transplantation than AKIN,38 be used for the evaluation of renal function and the
and it might predict long-term outcomes in patients with CKD staging should be used for the classification
multiple myeloma.39 Prospective studies are encouraged of patients with multiple myeloma with stabilised serum
to establish the optimal method of evaluation of acute creatinine concentrations (grade B recommendation). If
kidney injury in patients with multiple myeloma. available, the addition of cystatin C as a variable might
improve the CKD-EPI calculations (grade B recom-
Recommendations mendation). Baseline β2-microglobulin concentrations
All patients with multiple myeloma and renal impairment should be measured in all patients with multiple
should have serum creatinine, eGFR, electrolytes, and myeloma (grade A recommendation). For patients with
FLCs measurements together with total protein, urine acute kidney injury, the KDIGO, RIFLE, and AKIN
electrophoresis, and immunofixation of a sample from criteria should be used (grade C recommendation).

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KDIGO RIFLE AKIN KDIGO, RIFLE, and AKIN

Stage 1 (AKIN and KDIGO) Serum creatinine increase to 1·5–1·9 times Serum creatinine increase of ≥50% or eGFR Serum creatinine increase of ≥50% Urine output <0·5 mg/kg per h
or Risk (RIFLE) baseline or increase of ≥0·3 mg/dL decrease of >25% or increase of ≥0·3 mg/dL for 6 h
Stage 2 (AKIN and KDIGO) Serum creatinine increase to 2·0–2·9 Serum creatinine increase of ≥100% or eGFR Serum creatinine increase of ≥100% Urine output <0·5 mg/kg per h
or Injury (RIFLE) times baseline decrease of >50% for 12 h
Stage 3 (AKIN and KDIGO) Serum creatinine increase to 3·0 times Serum creatinine increase of ≥200%, or eGFR Serum creatinine increase of ≥200%, Urine output <0·3 mg/kg per h
or Failure (RIFLE) baseline, or increase to ≥4 mg/dL, or decrease of >75%, or serum creatinine increase or increase to ≥4·0 mg/dL with an for 24 h or anuria for 12 h
renal replacement therapy to ≥4·0 mg/dL with an acute increase of acute increase of ≥0·5 mg/dL from
≥0·5 mg/dL from baseline baseline, or renal replacement
therapy
Loss (RIFLE) ·· Complete loss of kidney function (need for ·· ··
renal replacement therapy) for >4 weeks
End-stage kidney disease ·· End stage kidney disease (need for renal ·· ··
(RIFLE) replacement therapy) for >3 months

AKIN=Acute Kidney Injury Network. eGFR=estimated glomerular filtration rate. KDIGO=Kidney Disease: Improving Global Outcomes. RIFLE=Risk, Injury, Failure, Loss, and End-stage kidney disease.

Table 2: Staging of acute kidney injury

casts per square millimetre on kidney biopsy, as

Baseline eGFR Best creatinine
(mL/min per clearance response highlighted in a large multicentre cohort of patients with
1·73 m²)* (mL/min) biopsy-proven myeloma cast nephropathy.51 Because of
Complete response <50 ≥60 the necessity of rapidly decreasing the production and
Partial response <15 30–59 serum concentrations of nephrotoxic FLCs, any
Minor response <15 15–29 interruption of anti-myeloma therapy, side-effects such
Minor response 15–29 30–59
as pre-existing infections, or haemodynamic instability
can be highly deleterious for renal recovery in these
eGFR=estimated glomerular filtration rate. *eGFR calculated with the Chronic patients and lead to definitive end stage kidney disease.
Kidney Disease Epidemiology Collaboration equation.
Notably, patients with myeloma cast nephropathy are
Table 3: Criteria for renal response to anti-myeloma treatment particularly frail and thus careful evaluation of the
efficacy and toxicity of chemotherapy is of paramount
importance in these patients. For patients requiring
Criteria for renal response dialysis, independence from dialysis has been associated
The primary aim of treatment of patients with multiple with prolonged survival.42,52
myeloma and renal impairment is the reversibility of
renal impairment, which is associated with improved Recommendations
patient outcomes.8 The IMWG criteria for renal response The IMWG criteria for the definition of renal response
to anti-myeloma treatment (table 3)40 are well established should be used in both clinical trials and daily clinical
and have been used in several studies internationally to practice (grade B recommendation).
assess renal response.41–47 In the presence of biopsy-
proven AL amyloidosis, specific renal response criteria Supportive care
should be used.48 Renal impairment due to multiple myeloma is
Almost all studies have highlighted that renal a medical emergency, and immediate initiation of
response depended on early, substantial reduction of effective anti-myeloma treatment is of utmost
the involved FLCs. In the MYRE study, serum FLC importance. Additionally, adequate supportive care is
concentrations less than 500 mg/L after the first cycle required for all patients with a suspicion of myeloma-
of chemotherapy were independently associated with induced renal impairment. Supportive care involves
renal response in patients needing dialysis.49 In patients appropriate fluid hydration (at least 3 L/day or 2 L/m²
who did not require dialysis, haematological response per day), which is crucial in individuals with fluid
in terms of FLCs reduction (at least partial response) depletion due to hypercalcaemia.53 Fluid balance should
within the first 6 months, AKIN stage 3, and pre- be carefully monitored, especially in patients with
existing mild-to-moderate CKD (eGFR 30–59 mL/min congestive heart failure. A fluid challenge is appropriate
per 1·73 m²) were independent predictors of renal for patients presenting with anuria. Urine alkalisation
outcome.50 has not shown its efficacy in the reversibility of renal
However, FLC response is not the sole determinant of impairment.53 The restoration of calcium homoeostasis
renal response, which also depends on several might be crucial for reversing renal impairment.
conditions, such as pre-existing CKD and histological Bisphosphonates and denosumab are approved for
parameters, particularly the mean number of cortical the treatment of myeloma-associated hypercalcaemia;

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however, bisphosphonates (both pamidronate and Mechanical approaches

zoledronic acid) are not recommended in patients with Mechanical approaches have been used in patients with
a creatinine clearance of less than 30 mL/min and multiple myeloma and renal impairment to rapidly
treatment with these agents should be started only upon reduce serum FLCs concentrations. The concomitant
GFR improvement, due to risk of renal injury.19 In administration of anti-myeloma treatment is crucial to
patients on chronic dialysis, with no option of GFR reduce monoclonal FLC production from malignant
reversal to rates higher than 30 mL/min per 1·73m², plasma cells. The additive value of plasmapheresis in
bisphosphonates might be used for the management of improving patient outcomes has been inconclusive in
myeloma-related bone disease. However, a single dose the era of conventional chemotherapy; however, the
of pamidronate for the management of hypercalcaemia efficacy of plasmapheresis seems to be reduced due to
does not increase the risk for nephrotoxicity, provided the total volume exchanged per session.58,59 High-cutoff
that dose and infusion methods are adapted to GFR haemodialysis is more effective in FLC removal because
value.54 Denosumab is safe in patients with multiple it allows for the removal of molecules up to 65 000 daltons.
myeloma and in patients with solid cancer and The combination of high-cutoff membranes with
renal impairment; nevertheless, the development of modern anti-myeloma treatments has led to more than
hypocalcaemia and hypophosphataemia requires close double haemodialysis independence rates compared
monitoring.19,55 High-dose steroids and calcitonin with plasma exchange.60–62 Two randomised controlled
can be administered safely. Furosemide is not advised, trials compared high-cutoff haemodialysis with standard
because it might promote cast formation in the renal high-flux haemodialysis in patients receiving bortezomib-
tubules.56 Nephrotoxic agents, including contrast agents, based regimens.49,63 Both the MYRE49 and the EuLITE63
renin–angiotensin–aldosterone system blockers, non- studies did not show a significant improvement
steroidal anti-inflammatory drugs, and some anti- with high-cutoff membranes in the rate of dialysis
biotics (eg, aminoglycosides), should be avoided or independence at 3 months on study. However, a benefit
discontinued in patients with multiple myeloma and was noted in the MYRE study at 6 months and 12 months
renal impairment.57 Bacterial infection should be ruled after study entry for patients with anuric renal failure.
out, or if confirmed, treated with antibiotic therapy. However, in the EuLITE study, overall survival was
Polypharmacy is common for patients with multiple inferior in patients undergoing high-cutoff haemodialysis
myeloma, especially when comorbidities are present; compared with patients undergoing standard high-flux
therefore, special attention should be given to haemodialysis.
appropriate dose adjustments for both anti-myeloma Treatment discontinuation is primarily due to
drugs (table 4) and concomitant medications. infections.63 Other mechanical approaches yet to be
evaluated in prospective studies include haemodialysis
Recommendations with adsorptive polymethyl-methacrylate dialysers,64
High-fluid administration (at least ≥3 L/day or haemodiafiltration with ultrafiltrate regeneration,65
2 L/m² per day) should be initiated together with anti- supra-haemodiafiltration with endogenous reinfusion
myeloma therapy (grade B recommendation). Urine after FLC adsorption,66 or continuous venovenous
alkalisation seems not to offer an advantage in the haemofiltration with high-cutoff filters.67 Patients with
reversal of renal impairment in patients with multiple irreversible end-stage renal impairment require long-
myeloma (grade B recommendation). Bisphosphonates term dialysis and have a poor prognosis.8
can reduce calcium concentrations in patients with In addition to the questionable efficacy, the optimal
hypercalcaemia, but neither pamidronate nor zoledronic timing of applying an extracorporeal approach is
acid should be used in patients with multiple myeloma debatable. In the MYRE study,49 patients initiated
and severe renal impairment (creatinine clearance treatment after a preinclusion period of up to 15 days
<30 mL/min; grade A recommendation). In patients on that included symptomatic measures and high-dose
chronic dialysis, with no option of GFR reversal to rates steroids. In the EuLITE study,63 patients initiated
higher than 30 mL/min per 1·73m², bisphosphonates treatment upfront, immediately after inclusion. Dialysis
might be used for the management of myeloma-related should be initiated in all patients with an indication to
bone disease (grade D recommendation). Denosumab treat acute kidney injury due to severe volume overload
might be useful in patients with hypercalcaemia and and electrolyte disorders, irrespective of the underlying
renal impairment, but calcium and phosphate myeloma. Otherwise, monoclonal cast nephropathy
concentrations should be closely monitored (grade B should be highly suspected or histologically confirmed
recommendation). Avoidance of nephrotoxic agents, to proceed with the mechanical removal of FLCs.68
such as aminoglycoside antibiotics, renin–angiotensin– Initial intensive supportive measures and correction of
aldosterone system blockers, furosemide, non-steroidal precipitating factors of acute kidney injury, such as low
anti-inflammatory drugs, and contrast agents, is highly hydration and hypercalcaemia, might be feasible for
recommended in patients with multiple myeloma and patients with stage 1 (AKIN and KDIGO) or Risk
renal impairment (grade A recommendation). (RIFLE) acute kidney injury and for patients with stage 2

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Creatinine clearance On dialysis

≥60 mL/min 30–59 mL/min 15–29 mL/min <15 mL/min
Dexamethasone (orally or 20–40 mg No dose modification needed No dose modification needed No dose modification needed No dose modification needed
intravenously)
Melphalan 0·15–0·25 mg/kg per day Reduction by 25% orally; high Reduction by 25% orally; high Reduction by 50% orally; high Reduction by 50% orally; high
orally; high dose: dose: 140 mg/m² dose: 140 mg/m² dose: 140 mg/m² intravenously dose: 140 mg/m²
200 mg/m² intravenously intravenously intravenously intravenously
Doxorubicin (intravenously) According to regimen No dose modification needed No dose modification needed No dose modification needed No dose modification needed
Cyclophosphamide (orally or According to regimen No dose modification needed No dose modification needed No dose modification needed* No dose modification needed
intravenously)
Bortezomib (subcutaneously) 1·3 mg/m² No dose modification needed No dose modification needed No dose modification needed No dose modification needed
Carfilzomib (intravenously) Loading dose/full dose: No dose modification needed No dose modification needed No dose modification needed No dose modification needed,
20/27 mg/m² or after dialysis
20/56 mg/m² or
20/70 mg/m²
Ixazomib (orally) 4 mg 4 mg 3 mg 3 mg 3 mg
Thalidomide (orally) 50–200 mg No dose modification needed No dose modification needed No dose modification needed No dose modification needed
Lenalidomide (orally) 25 mg per day 10 mg per day, can be 15 mg every other day or 5 mg per day, can be increased 5 mg per day after dialysis, can
increased to 25 mg per day if 10 mg per day, can be to 15 mg per day if no toxicity be increased to 15 mg per day
no toxicity occurs increased to 15 mg per day if occurs if no toxicity occurs
no toxicity occurs
Pomalidomide (orally) 4 mg per day No dose modification needed No dose modification needed No dose modification needed No dose modification needed,
after dialysis
Daratumumab 16 mg/kg intravenously No dose modification needed No dose modification needed No dose modification needed No dose modification needed
or 1800 mg
subcutaneously
Isatuximab (intravenously) 10 mg/kg No dose modification needed No dose modification needed No dose modification needed No dose modification needed
Elotuzumab (intravenously) 10 mg/kg No dose modification needed No dose modification needed No dose modification needed No dose modification needed
Belantamab mafodotin 2·5 mg/kg No dose modification needed Not determined yet Not determined yet Not determined yet
(intravenously)
Selinexor (orally) 80 mg No dose modification needed No dose modification needed Not determined yet Not determined yet
Idecabtagene vicleucel 260–500 × 10⁶ CAR- Not determined yet Not determined yet Not determined yet Not determined yet
(intravenously) positive, viable T cells
Ciltacabtagene autoleucel 0·5–1·0 × 10⁶ CAR- Not determined yet Not determined yet Not determined yet Not determined yet
(intravenously) positive, viable T cells
Teclistamab (subcutaneously) 1·5 mg/kg No dose modification needed Not determined yet Not determined yet Not determined yet
with creatinine clearance
>40 mL/min
Venetoclax: off-label for patients 800 mg per day orally No dose modification needed No dose modification needed Not determined yet Not determined yet
with t(11;14)(q13;q32)

There are several treatment regimens for each drug in terms of frequency and schedule, depending also on the treatment phase. CAR=chimeric antigen receptor. *Monitor patients with severe renal impairment
for toxicity. Decreased renal excretion in these patients might result in increased plasma concentrations of this drug and its metabolites, which could lead to increased toxicity.

Table 4: Dose modifications for anti-myeloma drugs in patients with renal impairment

(AKIN and KDIGO) or Injury (RIFLE) acute kidney improve the rate of dialysis independence (grade C
injury (table 2); however, close patient monitoring is recommendation). There is no difference in the rates
crucial to start dialysis in non-responders early. Prompt of dialysis independence between high-cutoff haemo-
diagnosis and treatment initiation is essential because dialysis and conventional high-flux haemodialysis at
delayed intervention might not reverse kidney damage, 3 months (grade C recommendation).
which would thus become irreversible.
Anti-myeloma therapy
Recommendations Renal impairment in patients with multiple myeloma,
Mechanical approaches alone do not improve especially upfront, is a potentially reversible condition
overall survival or haemodialysis independence even in and should be treated immediately. Newly diagnosed
patients with multiple myeloma and acute kidney patients with multiple myeloma and renal impairment
injury AKI because of monoclonal cast nephropathy have a high chance of improvement, whereas patients
(grade B recommendation). Mechanical approaches with relapsed or refractory multiple myeloma and renal
in combination with anti-myeloma therapy might impairment are more challenging to manage.

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Regimens based on high-dose steroids additive benefit of cyclophosphamide in the bortezomib–

Regimens with high-dose steroids include steroid doses dexamethasone regimen among patients with multiple
equivalent to at least 160 mg of dexamethasone for 4 days. myeloma and established acute kidney injury without the
A common regimen consists of 40 mg of dexamethasone need for dialysis.50 A tailored approach based on patient
administered 4 days on and 4 days off for three pulses in frailty is encouraged to optimise the balance between
a 28-day cycle and lead to renal responses in up to 65% of efficacy and toxicity.
patients.69,70 High-dose dexamethasone in the first month Carfilzomib is a second-generation proteasome inhibitor
of therapy has been associated with a more rapid renal and its combinations are highly effective in patients with
response in newly diagnosed patients with multiple relapsed or refractory multiple myeloma. Intravenous
myeloma and renal impairment treated with proteasome carfilzomib clearance, efficacy, and toxicity do not differ
inhibitors or immunomodulatory drugs.70,71 Intravenous among patients with normal renal function and those
methylprednisolone at equivalent dose to dexamethasone with varying degrees of renal impairment.87,88 A post-hoc
can be helpful, especially in patients with severe acute exploratory subgroup analysis of the ENDEAVOR
kidney injury, as an alternative to dexamethasone.72 randomised phase 3 study89 assessed the effectiveness and
However, patients should be carefully monitored, safety of carfilzomib–dexamethasone compared with
because this treatment is associated with increased risk bortezomib–dexamethasone in patients with varying
of infections. In patients with acute renal impairment degrees of renal impairment at baseline (table 5).
attributed to the underlying multiple myeloma, steroids Progression-free survival, overall survival, and overall
can be initiated before all investigations are reported and response rate improved in the carfilzomib–dexamethasone
before the administration of specific anti-myeloma group across renal subgroups. Approximately 15% of
treatment (panel opinion). patients with a creatinine clearance of 15–50 mL/min had
complete renal response.89 A subgroup analysis of the
Recommendations phase 3 ARROW trial showed that once weekly
The recommended dose for high-dose dexamethasone administration of carfilzomib–dexamethasone (70 mg/
(orally or intravenously) is 40 mg/day (20 mg for patients m²) improved progression-free survival and overall
aged ≥75 years), 4 days on and 4 days off for three pulses response rate across all renal subgroups (creatinine
during the first cycle of therapy, and then according to clearance 30–49 mL/min, 50–79 mL/min, and
the treatment protocol (grade B recommendation). ≥80 mL/min) compared with twice per week carfilzomib–
dexamethasone (27 mg/m²).103 A large real-world study
Regimens based on proteasome inhibitors compared renal response rates among patients with
Bortezomib-based combinations are the mainstay of first- relapsed or refractory multiple myeloma and renal
line treatment combinations in patients with multiple impairment (eGFR ≤50 mL/min per 1·73m²) treated with
myeloma. Bortezomib has long been regarded as the gold carfilzomib–dexamethasone (n=543) or bortezomib–
standard of therapy for patients with multiple myeloma dexamethasone (n=1005) in the second through fourth
and renal impairment, owing to its non-renal metabolism, line of therapy.47 Patients undergoing second-line therapy
favourable effects on the kidney (improved kidney who received carfilzomib–dexamethasone had
function), and the accumulating data supporting its substantially higher rates of renal overall response
effectiveness in this patient population, which was first (51·4% vs 39·6%; p<0·0001) and renal complete response
observed in the SUMMIT trial73 and then in the APEX (26·6% vs 22·2%; p=0·0229) than patients receiving
study.74 Bortezomib-based regimens generate rapid bortezomib–dexamethasone. The results were similar for
and deep haematological and renal responses, with patients with an eGFR of 15 mL/min per 1·73m² or less
possible reversal of renal impairment and dialysis and for patients receiving third-line and fourth-line
independence.46,71,75–84 Bortezomib-based induction and treatments.47 However, carfilzomib-related renal
high-dose melphalan therapy with autologous haemato- complications including thrombotic microangiopathy,
poietic stem-cell transplantation (HSCT) improve the albuminuria, and grade 3 acute kidney injury have been
prognosis of patients with multiple myeloma presenting reported.104 Furthermore, in the FOCUS study, renal
with renal impairment at baseline.85 In randomised failure was more frequently observed in patients receiving
controlled trials, the subcutaneous administration of carfilzomib monotherapy who had low GFR and
bortezomib provided similar results to the intravenous proteinuria than in patients receiving cyclophosphamide.105
injection in patients with multiple myeloma and renal Therefore, carfilzomib should be administered with
impairment, although intravenous administration with caution in patients with impaired renal function and
hydration in patients with severe acute kidney injury might bortezomib remains the first choice of proteasome
be a suitable option, due to a possible more rapid effect.79,86 inhibitor in patients with multiple myeloma and renal
Bortezomib-based triplet combinations might improve impairment in the absence of disease refractoriness
renal response and dialysis discontinuation rates compared to bortezomib.
with the bortezomib–dexamethasone combination.42,45 Ixazomib is an oral proteasome inhibitor for patients
However, a randomised controlled trial did not show any with relapsed or refractory multiple myeloma.

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Additionally, patients with mild-to-moderate renal a low renal clearance,107 a lower starting dose (3 mg) is
impairment (creatinine clearance 30–59 mL/min) indicated for individuals with a creatinine clearance of
comprised 25% of the patients receiving ixazomib– less than 30 mL/min.108
lenalidomide–dexamethasone in the phase 3
TOURMALINE-MM1 trial.106 Although subgroup Recommendations
analyses were not done, the study results show that the Bortezomib-based regimens remain the cornerstone of
safety and efficacy profile of the regimen can be safely the management of myeloma-related renal impairment
extended to this patient group. Despite ixazomib having (grade A recommendation). Bortezomib should be

Cutoff for renal impairment* Median progression-free Median overall survival Overall Complete Median Grade ≥3
survival response rate renal time to adverse
(%) response complete events (%)
(%) renal
response
(weeks)
Months Hazard ratio Months Hazard ratio
(95% CI) (95% CI)
Newly diagnosed patients with multiple myeloma
ALCYONE90
DaraVMp (n=150) ≥30 to <60 NR 0·36 (0·24–0·56) NR NA 89% NA NA 47%
VMp (n=145) ≥30 to <60 16·9 1 (ref) NA NA 73% NA NA 42%
CASSIOPEIA91
DaraVTd (n=212) ≥40 to <90 NA 0·37 (0·21–0·66) NA NA NA NA NA NA
VTd (n=226) ≥40 to <90 NA 1 (ref) NA NA NA NA NA NA
MAIA (lenalidomide 25 mg)92
DaraRd (n=60) ≥30 to <60 NR 0·42 (0·24–0·72) NR 0·37 (0·19–0·73) NA NA NA NA
Rd (n=62) ≥30 to <60 35·4 1 (ref) NR 1 (ref) NA NA NA NA
MAIA (lenalidomide <25 mg)92
DaraRd (n=98) ≥30 to <60 49·1 0·56 (0·38–0·83) 62·8 0·81 (0·52–1·26) NA NA NA NA
Rd (n=75) ≥30 to <60 24·9 1 (ref) 54·8 1 (ref) NA NA NA NA
Patients with relapsed or refractory multiple myeloma
ASPIRE93
KRd (n=79) ≥30 to <60 NA NA NA 0·72 (0·51–1·02) NA NA NA NA
Rd (n=82) ≥30 to <60 NA NA NA 1 (ref) NA NA NA NA
ENDEAVOR89
Kd (n=85) ≥15 to <50 14·9 0·49 (0·32–0·76) 42·1 0·66 (0·44–0·99) 74·1% 15·3% 8·1 87%
Vd (n=99) ≥15 to <50 6·5 1 (ref) 23·7 1 (ref) 49·5% 14·1% 6·4 79%
MM-00394
Pd (n=93) ≥30 to <60 4·0 0·48 (0·33–0·70) 10·4 0·65 (0·44–0·96) 28% 32% NA NA
Plowd (n=56) ≥30 to <60 1·9 1 (ref) 4·9 1 (ref) 11% 43% NA NA
OPTIMISMM95
PVd (n=35) ≥30 to <60 15·1 0·67 (0·34–1·34) NA NA 91·4% NA 3·1† NA
Vd (n=28) ≥30 to <60 9·5 1 (ref) NA NA 53·6% NA 4·6† NA
POLLUX96
DaraRd (n=80) ≥30 to <60 33·6 0·41 (0·26–0·65) NR NA 91% NA NA NA
Rd (n=65) ≥30 to <60 11·3 1 (ref) NR NA 68% NA NA NA
CASTOR97
DaraVd (n=57) ≥20 to ≤60 NR 0·55 (0·30–1·02) NA NA NA NA NA NA
Vd (n=70) ≥20 to ≤60 6·5 1 (ref) NA NA NA NA NA NA
APOLLO98
DaraPd (n=40) ≥30 to ≤60 12·1 0·59 (0·35–0·99) NA NA NA NA NA NA
Pd (n=47) ≥30 to ≤60 6·1 1 (ref) NA NA NA NA NA NA
CANDOR99
DaraKd (n=38) ≥15 to <50 NA 0·44 (0·19–1·00) NA NA NA NA NA NA
Kd (n=27) ≥15 to <50 NA 1 (ref) NA NA NA NA NA NA
(Table 5 continues on next page)

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Cutoff for renal impairment* Median progression-free Median overall survival Overall Complete Median Grade ≥3
survival response rate renal time to adverse
(%) response complete events (%)
(%) renal
response
(weeks)
Months Hazard ratio Months Hazard ratio
(95% CI) (95% CI)
(Continued from previous page)
ICARIA-MM100
IPd (n=55) eGFR ≥30 to <60 mL/min per 1·73 m² 9·5 0·50 (0·30–0·85) NR 0·53 (0·30–0·96) 56·4% 71·9% 3·4 91%
Pd (n=49) eGFR ≥30 to <60 mL/min per 1·73 m² 3·7 1 (ref) 11·6 1 (ref) 24·5% 38·1% 7·3 79%
IKEMA101
IKd (n=43) eGFR ≥15 to <60 mL/min per 1·73 m² NR 0·27 (0·11–0·66) NA NA 93·1% 52·0% 7·8 79·1%
Kd (n=18) eGFR ≥15 to <60 mL/min per 1·73 m² 13·4 1 (ref) NA NA 61·1% 30·8% NA 77·8%
BOSTON102
XVd (n=21; n=35) ≥20 to <40; ≥40 to <60 7·6; 16·6 0·62 (p=0·13); NR; NR 0·74 (p=0·26); 81·0%; 80·0% NA NA 66·7%; 42·9%
0·49 (p=0·028) 0·55 (p=0·080)
Vd (n=26; n=44) ≥20 to <40; ≥40 to <60 4·3; 7·6 1 (ref); 1 (ref) 19·1; 21·2 1 (ref); 1 (ref) 53·8%; 59·1% NA NA 40·0%; 47·6%

DaraKd=daratumumab plus Kd. DaraRd=daratumumab plus Rd. DaraVd=daratumumab plus Vd. DaraVMp=daratumumab plus VMp. DaraVTd=daratumumab plus VTd. eGFR=estimated glomerular filtration rate.
IPd=isatuximab–pomalidomide–dexamethasone. IKd=isatuximab–carfilzomib–dexamethasone. Kd=carfilzomib–dexamethasone. KRd=carfilzomib–lenalidomide–dexamethasone. NA=not available. NR=not
reached. Pd=pomalidomide–dexamethasone. Plowd=pomalidomide–low-dose dexamethasone. PVd=pomalidomide–bortezomib–dexamethasone. Rd=lenalidomide–dexamethasone. Vd=bortezomib–
dexamethasone. VMp=bortezomib–melphalan–prednisone. VTd=bortezomib–thalidomide–dexamethasone. XVd=selinexor–bortezomib–dexamethasone. *Creatinine clearance cutoff (mL/min), unless otherwise
stated. †Time to first improvement in renal function.

Table 5: Subgroup analyses of patients with multiple myeloma and renal impairment in selected phase 3 studies

initiated at the standard dose of 1·3 mg/m² on days 1, 4, 8, Because thalidomide is not eliminated by the kidneys, no
and 11 of a 3-week cycle (grade A recommendation) and dosage adjustments are required. The anticipated renal
high-dose dexamethasone should be administered at least recovery with thalidomide-based regimens ranges from
for the first month of therapy (grade B recommendation). up to 75% in newly diagnosed patients with multiple
Subcutaneous administration of bortezomib has similar myeloma and 60% in patients with relapsed or refractory
efficacy to intravenous use (grade A recommendation). multiple myeloma.71,109
Bortezomib-based triplet combinations might improve Lenalidomide is a second-generation immuno-
renal outcomes in some patients to ensure an optimal modulatory drug that has been incorporated into the
balance between efficacy and toxicity (grade C recom- whole treatment continuum of multiple myeloma both
mendation). Carfilzomib is safe and effective in patients in the first and in the subsequent lines of therapy.
with relapsed or refractory multiple myeloma and renal Lenalidomide is eliminated unaltered in the urine and
impairment (grade A recommendation for creatinine should be dosed according to renal function.110 Dose
clearance ≥15 mL/min; grade B recommendation for modifications do not compromise efficacy and ensure
creatinine clearance <15 mL/min) without the need for safety for both newly diagnosed patients with multiple
dose adjustments. Close monitoring is important for early myeloma and patients with relapsed or refractory
identification and prompt management of carfilzomib- multiple myeloma.109,111 The phase 1/2 PrECOG study
related renal complications. Ixazomib can be safely showed the feasibility of administering lenalidomide at
administered in combination with lenalidomide and full dose (25 mg) to patients with a creatinine clearance
dexamethasone in patients with relapsed or refractory of 30 mL/min or higher and up to a maximum of 15 mg
multiple myeloma and a creatinine clearance of daily to patients with a creatinine clearance of less
30 mL/min or higher (grade A recommendation). A lower than 30 mL/min, including patients on dialysis.112
starting dose of 3 mg is indicated for individuals with A retrospective analysis of registrational studies of
a creatinine clearance of less than 30 mL/min (grade B lenalidomide–dexamethasone showed that the majority
recommendation). of patients with multiple myeloma and moderate-to-
severe renal impairment improved by at least one level
Regimens based on immunomodulatory drugs in creatinine clearance (table 3).113 However, patients
Thalidomide is one of the first anti-myeloma drugs with severe renal impairment had an increased incidence
and it is still used in combination with other agents of toxic effects and shorter overall survival. The efficacy
(eg, bortezomib–thalidomide–dexamethasone) in newly and safety of lenalidomide–dexamethasone have been
diagnosed patients with multiple myeloma and in shown in phase 2 trials,114,115 and in real-world studies of
patients with relapsed or refractory multiple myeloma. patients with multiple myeloma and renal impairment

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Cutoff for renal Median Median (range) Median (95% CI) Median (95% CI) Overall Renal Adverse events
impairment* (range) eGFR, mL/min progression-free overall survival, response response
previous per 1·73m² survival, months months rate (%) rate (%)
lines of
therapy
Grade ≥3 Serious
(%) (%)
MM-013124
Pomalidomide–dexamethasone (n=33) eGFR 30 to <45 mL/min 3 (2–8) 38·8 (31·0–47·0) 6·5 (4·60–10.62) 16·4 (7·79–25·18) 39·4% 18·2% NA 54·5%
per 1·73m²
Pomalidomide–dexamethasone (n=34) eGFR <30 mL/min per 4 (1–10) 22·2 (8·0–33·5) 4·2 (2·79–6·51) 11·8 (6·35–13·45) 32·4% 35·3% NA 61·8%
1·73m²
Pomalidomide–dexamethasone (n=14) eGFR <30 mL/min per 4 (2–5) 8·9 (4·0–21·0) 2·4 (0·95–6·41) 5·2 (1·81–9·67) 14·3% 7·1% NA 85·7%
1·73m² requiring
haemodialysis
DARE41
Daratumumab–dexamethasone (n=38) eGFR <30 mL/min per 3 (2–6) 12 (4–58) 11·8 (2·8–20·8) 24·5 (5·5–NR) 47·4% 18·4% 63·2% 28·9%
1·73m²
DREAMM-2125
Belantamab mafodotin 2·5 mg/kg (n=24) ≥30 to <60 7 (3–21) NA 3·7 (1·0–NR) NA 33% NA NA 50%
Belantamab mafodotin 3·4 mg/kg (n=22) ≥30 to <60 6 (4–21) NA 3·4 (0·8–6·4) NA 27% NA NA 50%
STORM126
Selinexor–dexamethasone (n=14) ≥20 to <40 7 (3–18) NA NR 6·1 35·7% 43%† 73% 73%
Selinexor–dexamethasone (n=25) ≥40 to <60 7 (3–18) NA 4·7 5·8 16·0% 38%† 60% 68%

eGFR=estimated glomerular filtration rate. NA=not available. NR=not reached. *Creatinine clearance cutoff (mL/min), unless otherwise stated. †Increase in creatinine clearance by at least one category level from
baseline.

Table 6: Selected phase 2 studies reporting outcomes of patients with relapsed or refractory multiple myeloma and renal impairment

including end-stage renal impairment.116–118 Lenalidomide 45 mL/min per 1·73 m² or higher.123 The phase 2 MM-013
should be avoided in patients with AL amyloidosis and trial prospectively evaluated pomalidomide plus low-dose
proteinuria.119 Of note, lenalidomide dose adaptation is dexamethasone in 81 patients with relapsed or refractory
possible only in patients with stable renal function. In multiple myeloma and moderate renal impairment (eGFR
patients with acute kidney injury, whose serum 30–45 mL/min per 1·73 m²), severe renal impairment
creatinine concentrations can rise every day, dose (eGFR <30 mL/min per 1·73 m²), or on dialysis. All
adaptation is more difficult, because the eGFR cannot be patients had substantial rates of disease control with a
easily estimated, except for patients requiring dialysis. manageable safety profile, although the patients with
Pomalidomide is a third-generation immunomodulatory severe renal impairment had a shorter overall survival
drug that is administered to patients with relapsed (table 6).124
or refractory multiple myeloma after exposure to Iberdomide is a new, potent cereblon E3 ligase
lenalidomide. Pomalidomide is extensively metabolised by modulator with enhanced tumoricidal and immune-
the liver, with only minimal renal clearance of the active stimulatory effects compared with immunomodulatory
drug.120 No dose modification is necessary for patients with drug. Iberdomide is extensively metabolised, constituting
renal impairment, in whom it should be administered only 16% of intact drug in urine.127 In a sub-analysis from
after dialysis.121 A post-hoc analysis of the MM-003 trial the phase 1/2 study CC-220-MM-001 (NCT02773030), the
showed that pomalidomide plus low-dose dexamethasone combination of iberdomide plus dexamethasone
resulted in similar progression-free survival, overall produced similar efficacy, safety, and pharmacokinetics
survival, renal response rates, and toxicity in patients with results in patients with relapsed or refractory multiple
a creatinine clearance of 30–59 mL/min (table 5) and in myeloma with no renal impairment, mild renal
those with a creatinine clearance of 60 mL/min or higher.94 impairment, or moderate renal impairment. Thus,
A pooled analysis of three clinical trials including patients iberdomide dose modifications are not required for
with relapsed or refractory multiple myeloma and patients with mild-to-moderate renal impairment. In the
moderate renal impairment showed similar results.122 CC-220-MM-001 trial, no patient had a creatinine
A real-world study showed no differences in survival clearance of less than 30 mL/min and, thus, iberdomide
outcomes and toxicity with pomalidomide plus low-dose dosing in patients with severe renal impairment or
dexamethasone between patients with an eGFR of less kidney failure requires further study.128 Iberdomide is not
than 45 mL/min per 1·73 m² and those with an eGFR of approved yet for use in patients with multiple myeloma.

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Recommendations upfront setting and at first relapse in patients with

Thalidomide is effective in patients with multiple myeloma a creatinine clearance of less than 50 mL/min improve
and renal impairment (grade B recommendation) and complete renal response rates and survival outcomes
should be given without dose modifications (grade A (grade B recommendation). Triplet combinations
recommendation). Lenalidomide with dexamethasone (eg, pomalidomide–bortezomib–dexamethasone and
is effective and safe in patients with multiple myeloma carfilzomib–lenalidomide–dexamethasone improve rates
and renal impairment (grade B recommendation). of haematological and renal response along with
Lenalidomide should be administered with dose survival outcomes compared with doublet combinations
adjustments according to creatinine clearance (grade B (eg, bortezomib–dexamethasone and lenalidomide–
recommendation). Patients with a creatinine clearance of dexamethasone) in patients with relapsed or refractory
less than 30 mL/min, whether on dialysis or not, can multiple myeloma and a creatinine clearance of
receive up to 15 mg daily (grade B recommendation). 30–59 mL/min (grade B recommendation).
Pomalidomide with dexamethasone is safe and effective in
patients with relapsed or refractory multiple myeloma and Regimens based on monoclonal antibodies
renal impairment, including patients on dialysis (grade A The introduction of monoclonal antibodies for the
recommendation for creatinine clearance ≥45 mL/min; treatment of multiple myeloma, as part of quadruplet
grade B recommendation for creatinine clearance combinations in newly diagnosed patients and as
<30 mL/min). part of triplet combinations in patients with relapsed
disease, have further enhanced patient outcomes.
Regimens based on proteasome inhibitors and The anti-CD38 monoclonal antibody daratumumab
immunomodulatory drugs with dexamethasone was administered to patients with
Upfront treatment with bortezomib–lenalidomide– relapsed or refractory multiple myeloma and severe renal
dexamethasone can improve renal function in up to impairment (eGFR <30 mL/min per 1·73 m² or on
64% of patients presenting with an eGFR of less than dialysis) in the phase 2 DARE study (table 6).41 The study
60 mL/min and in patients not requiring autologous included 38 patients with eGFR <30 mL/min per 1·73 m²;
HSCT.129,130 Bortezomib–thalidomide–dexamethasone is the overall response rate was 47% and the 6-month
an efficacious and safe regimen in patients with multiple progression-free survival was 54%. The overall response
myeloma and renal impairment.70 An analysis including rate among those requiring dialysis (n=17) was 47%.
1772 newly diagnosed patients with multiple myeloma The renal response rate was 18% in patients with
and an eGFR (with the Modification of Diet in Renal eGFR <30 mL/min per 1·73 m².41 Case reports132–135 and
Disease formula) of less than 50mL/min per 1·73 m² case series136,137 of dialysis-dependent patients with
from a US nationwide electronic database showed that relapsed or refractory multiple myeloma who received
patients who received a regimen including a proteasome daratumumab-based treatment indicated consistent ben-
inhibitor and an immunomodulatory drug in the first and efit with reduced dialysis frequency or dialysis indepen-
second line of treatment were significantly more likely to dence. In a retrospective study, daratumumab-based
have a complete renal response and improved overall regimens improved progression-free survival in patients
survival than those who did not receive either treatment.12 with relapsed or refractory multiple myeloma regardless
A post-hoc analysis of the phase 3 OPTIMISMM study of renal function (eGFR <30 mL/min per 1·73 m² vs
showed that pomalidomide–bortezomib–dexamethasone 30–59 mL/min per 1·73 m² vs ≥60 mL/min per 1·73 m²),
improved overall response rate, progression-free survival, whereas 41% of patients with an eGFR of 30–59 mL/min
and time to improvement in renal function with no new per 1·73m² had a renal response.138 A pooled analysis of
safety signals compared with bortezomib–dexamethasone the pivotal phase 1/2 study and the supporting phase 2
in patients with relapsed or refractory multiple myeloma trial that led to the approval of daratumumab monotherapy
and a creatinine clearance of less than 60 mL/min in patients with relapsed or refractory multiple myeloma
(table 5).95,131 Carfilzomib–lenalidomide–dexamethasone reported similar overall response rates between patients
improved overall survival compared with lenalidomide– with a creatinine clearance of 30–60 mL/min and those
dexamethasone in the final analysis of the phase 3 with a creatinine clearance higher than 60 mL/min.139,140
ASPIRE study in patients with relapsed or refractory Daratumumab-based triplet combinations and quadru-
multiple myeloma and a creatinine clearance of plet combinations are efficacious and safe in patients
30–59 mL/min or of 60 mL/min or higher.93 Overall, with multiple myeloma and renal impairment (table 5).
triplet combinations are preferred over doublet In the phase 3 ALCYONE study,90 daratumumab–
combination because of superior outcomes, provided that bortezomib–melphalan–prednisone improved overall
the patient is fit enough to receive a triplet combination. response rates, minimal residual disease (MRD)
negativity rates, and progression-free survival without
Recommendations safety issues compared with bortezomib–melphalan–
Triplet combinations including a proteasome inhibitor, prednisone in newly diagnosed patients with multiple
an immunomodulatory drug, and a steroid in the myeloma and a creatinine clearance of 40–60 mL/min.

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In the phase 3 CASSIOPEIA study,91 daratumumab– isatuximab–pomalidomide–dexamethasone, but they

bortezomib–thalidomide–dexamethasone improved were manageable.100 In the phase 3 IKEMA study,101
overall response rates and progression-free survival isatuximab–carfilzomib–dexamethasone improved over-
compared with bortezomib–thalidomide–dexamethasone all response rate, MRD negativity rate, and progression-
in newly diagnosed patients with multiple myeloma and free survival compared with carfilzomib–dexamethasone
a creatinine clearance of 40–90 mL/min. In the in patients with relapsed or refractory multiple myeloma
phase 3 MAIA study,92 daratumumab–lenalidomide– and an eGFR of 15–60 mL/min per 1·73m². Complete
dexamethasone improved survival outcomes compared renal response rates were 52% with isatuximab–
with lenalidomide–dexamethasone in newly diagnosed carfilzomib–dexamethasone and 31% with carfilzomib–
patients with multiple myeloma and a creatinine clear- dexamethasone (table 5).101
ance of 30–60 mL/min. In the phase 3 CASTOR trial,97 Elotuzumab is an anti-SLAMF7 monoclonal anti-
daratumumab–bortezomib–dexamethasone improved body approved with lenalidomide–dexamethasone
progression-free survival compared with bortezomib– or pomalidomide plus low-dose dexamethasone.
dexamethasone in patients with relapsed or refractory Elotuzumab–lenalidomide–dexamethasone is adminis-
multiple myeloma and a creatinine clearance of tered to patients with relapsed or refractory multiple
20–60 mL/min. In the phase 3 CANDOR trial,99 myeloma and a creatinine clearance of 30 mL/min
daratumumab–carfilzomib–dexamethasone prolonged or higher, whereas elotuzumab–pomalidomide–
progression-free survival compared with carfilzomib– dexamethasone is given to patients with relapsed or
dexamethasone in patients with relapsed or refractory refractory multiple myeloma and a creatinine clearance
multiple myeloma and a creatinine clearance of 45 mL/min or higher.142,143 In a phase 1b study,144,145
of 15–50 mL/min. In the phase 3 POLLUX trial,96 elotuzumab–lenalidomide–dexamethasone was effec-
daratumumab–lenalidomide–dexamethasone increased tive and well tolerated by patients with multiple
progression-free survival compared with lenalidomide– myeloma and severe renal impairment including end-
dexamethasone in patients with relapsed or refractory stage renal impairment.
multiple myeloma and a creatinine clearance of
30–60 mL/min. In the phase 3 APOLLO trial,98 Recommendations
daratumumab–pomalidomide–dexamethasone Daratumumab with dexamethasone is safe and effective
improved progression-free survival compared with in patients with multiple myeloma and renal impairment,
pomalidomide plus low-dose dexamethasone in patients including those on dialysis (grade B recommendation).
with relapsed or refractory multiple myeloma and Daratumumab-based regimens are safe and effective
a creatinine clearance of 30–60 mL/min. In general, the for newly diagnosed patients with multiple myeloma
balance between efficacy and toxicity of quadruplet and a creatinine clearance of 40 mL/min or higher
therapy in patients with multiple myeloma and severe (daratumumab–bortezomib–melphalan–prednisone and
acute kidney injury remains poorly documented, in daratumumab–bortezomib–thalidomide–dexameth-
the absence of dedicated studies that are needed. asone) or of 30 mL/min or higher (daratumumab–
In newly diagnosed patients with multiple myeloma, lenalidomide–dexamethasone; grade B recommendation).
daratumumab–bortezomib–dexamethasone, assessment Anti-CD38-based triplet combinations are safe and
of FLC response every week, and reinforcement at the effective in patients with relapsed or refractory mul-
second cycle with an immunomodulatory drug might tiple myeloma and moderate-to-severe renal impairment
offer the best results (panel opinion). This treatment has (proteasome inhibitors: daratumumab–bortezomib–
to be proven in prospective studies. dexamethasone, daratumumab–carfilzomib–dexameth-
Isatuximab is another anti-CD38 monoclonal antibody asone, and isatuximab–carfilzomib–dexamethasone)
with high efficacy and safety in triplet combinations for or moderate renal impairment (immunomodulatory
patients with relapsed or refractory multiple myeloma drugs: daratumumab–lenalidomide–dexamethasone,
and renal impairment. In the phase 3 ICARIA-MM daratumumab–pomalidomide–dexamethasone, and
study,100,141 isatuximab–pomalidomide–dexamethasone isatuximab–pomalidomide–dexamethasone; grade B rec-
improved overall response rate, MRD negativity ommendation). Elotuzumab–lenalidomide–dexameth-
rate, and progression-free survival compared with asone is well tolerated and effective in patients with
pomalidomide plus low-dose dexamethasone in patients relapsed or refractory multiple myeloma and renal
with an eGFR of 30–60 mL/min per 1·73m², in addition impairment (grade C recommendation).
to its efficacy in the intent-to-treat overall population.
Complete renal response rates were 72% with Autologous HSCT
isatuximab–pomalidomide–dexamethasone and 38% High-dose melphalan followed by autologous HSCT
with pomalidomide plus low-dose dexamethasone, and remains a standard of care for eligible, newly diagnosed
isatuximab–pomalidomide–dexamethasone shortened patients with multiple myeloma. Autologous HSCT is
the median time to renal response (table 5). Treatment- feasible in patients with stable renal impairment, but
emergent toxicities were more frequent with not in patients with acute kidney injury, with a potential

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dose adjustment of melphalan from 200 mg/m² to of the phase 3 BOSTON study showed that, compared
140 mg/m², although data show the safety of melphalan with bortezomib–dexamethasone, selinexor–bortezomib–
at 200 mg/m².146–148 All panellists would consider dexamethasone significantly improved the overall
reducing the melphalan dose to 140 mg/m² when the response rate in patients with relapsed or refractory
eGFR is less than 30 mL/min per 1·73 m². multiple myeloma and different levels of renal function
In the era of bortezomib-based and daratumumab- (creatinine clearance 20 mL/min to <40 mL/min,
based induction regimens, mortality related to 40 mL/min to <60 mL/min, and ≥60 mL/min; table 5).102
transplantation is similar to that of patients without renal
impairment.148–150 Autologous HSCT might result in CAR T-cell therapy
improvement in renal function in up to a third of patients Chimeric antigen receptor (CAR) T cells targeting BCMA
and dialysis independence in more than a quarter on myeloma cells have been approved for relapsed or
of patients.146,147,151 Induction with new agents and refractory multiple myeloma because of significantly
subsequent autologous HSCT might overcome the improved outcomes in triple-class refractory patients
adverse prognostic effect of renal impairment at after at least four previous lines of therapy. Registrational
diagnosis.149,152 In a small study with 34 patients studies of idecabtagene vicleucel (KarMMA)154 and
undergoing haemodialysis,153 high-dose melphalan was ciltacabtagene autoleucel (CARTITUDE-1)155 included
given on a single day in a dose of 100 mg/m² and showed patients with adequate renal function and a creatinine
equivalent efficacy with high-dose melphalan 200 mg/m² clearance of 45 mL/min or higher154 and of 40 mL/min or
and manageable toxicity. higher,155 which is mainly due to the use of fludarabine as
lymphodepletion agent. A post-hoc analysis of pooled
Recommendations data from two phase 1 studies of distinct anti-BCMA
High-dose melphalan followed by autologous HSCT is CAR T-cell treatments showed that patients with renal
safe and effective in eligible, newly diagnosed patients dysfunction (eGFR 30–89 mL/min per 1·73 m²) showed
with multiple myeloma and stable renal impairment an improvement in eGFR; however, they had a worse
(grade B recommendation). A reduced (100 mg/m² or prognosis compared with patients with normal renal
140 mg/m²) or full (200 mg/m²) dose of melphalan can function.156 Another report including seven patients with
be administered depending on the severity of renal relapsed or refractory multiple myeloma and an eGFR
impairment (grade C recommendation). of 15–29 mL/min per 1·73 m² showed 100% overall
response rate and 100% renal response rates.157
Antibody-drug conjugates Fludarabine should be reduced to 24 mg/m² for patients
Belantamab mafodotin is an antibody-drug conjugate with an eGFR of 30–70 mL/min per 1·73 m² due to risk
targeting B-cell maturation antigen (BCMA) and has for nephrotoxicity.158 No dosing recommendation is
anti-myeloma activity in triple-class refractory available for patients with an eGFR of less than
patients after exposure to a proteasome inhibitor, an 30 mL/min per 1·73 m².
immunomodulatory drug, and an anti-CD38 monoclonal
antibody. A post-hoc analysis of the DREAMM-2 study125 Bispecific T-cell engagers
showed that belantamab mafodotin resulted in similar Bispecific T-cell engagers are new and promising anti-
overall response rate, progression-free survival, and myeloma immunotherapy approaches that might result
toxicities across patient groups according to renal in deep and durable responses in patients with relapsed
function (eGFR 90 mL/min per 1·73 m² vs or refractory multiple myeloma. Teclistamab has been
60–89 mL/min per 1·73 m² vs 30–59 mL/min per 1·73 approved for the management of relapsed or refractory
m²). An ongoing study (DREAMM-12) will assess the multiple myeloma, whereas others (eg, talquetamab or
pharmacokinetic profile and safety in patients with elranatamab) are near approval. All reported studies so
severe and end-stage renal impairment. far include patients with a creatinine clearance higher
than 40 mL/min with no substantial renal toxicity.159,160
XPO1 inhibitors However, studies in patients with moderate-to-severe
Selinexor is an exportin 1 inhibitor for patients renal impairment are highly anticipated.159
with relapsed or refractory multiple myeloma and is
administered orally. A post-hoc analysis of the phase 2b Recommendations
STORM trial showed that selinexor–dexamethasone Belantamab mafodotin is well tolerated and effective in
resulted in similar overall response rate regardless patients with relapsed or refractory multiple myeloma
of baseline renal function of heavily pretreated and moderate renal impairment (grade C recommen-
(penta-refractory) patients with relapsed or refractory dation). Selinexor-based regimens are well tolerated and
multiple myeloma (creatinine clearance 20 mL/min to effective in patients with relapsed or refractory multiple
<40 mL/min, 40 mL/min to <60 mL/min, and myeloma and moderate-to-severe renal impairment
≥60 mL/min), whereas an increase in creatinine clearance (grade C recommendation). Additional studies are
became evident in up to 67% of patients.126 A sub-analysis needed to establish the safety of CAR T-cells and

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bispecific T-cell engagers in patients with multiple evaluation, the exclusion of patients with severe renal
myeloma and moderate-to-severe renal impairment. impairment with an eGFR of less than 30 mL/min from
Ciltacabtagene autoleucel and idecabtagene vicleucel clinical trials, the inappropriate use of equations developed
seem to be safe in patients with a creatinine clearance for estimating renal function in CKD in patients with
equal to or higher than 40 mL/min and 45 mL/min, acute kidney injury, and the differential diagnosis of renal
respectively, whereas teclistamab is well tolerated impairment in patients with multiple myeloma.11
in patients with a creatinine clearance higher than Prospective data on patients with renal impairment
40 mL/min (grade C recommendation). exploring renal outcomes are scarce, which are essential
to formulate strong recommendations tailored for patients
Kidney transplantation with severe renal impairment. Thus, we highly encourage
Kidney transplantation has been offered to a few eligible future research in this field.
patients with long-term myeloma control and end-stage Several regimens offer both myeloma and renal
renal impairment who have previously undergone responses and increase survival in patients with multiple
autologous HSCT and the results are encouraging.161–164 myeloma and renal impairment. However, the optimal
A multidisciplinary expert approach is essential therapy, especially in patients with relapsed or refractory
to manage the adverse events from the combined multiple myeloma, has not yet been established.
immunosuppressive treatment and anti-myeloma Initiation of effective treatment is crucial; all new drugs
therapy. The available data do not suggest the best time to including the new generation immunotherapy can be
transplantation or whether immunosuppression after administered to patients with renal impairment. No
kidney transplantation might increase the risk of patient with renal impairment should be prevented from
myeloma relapse. All but one member of the panel effective treatment regimens.
suggest that, in eligible patients, the presence of sustained Contributors
MRD negativity at 2 years might signify a suitable time MAD and ET conceptualised and designed the study and wrote the first
point for kidney transplantation, if there is an available draft of the manuscript. All authors collected, assembled, analysed, and
interpreted the data. All authors reviewed and edited the manuscript and
organ. Although this suggestion is not supported by data had final responsibility for the decision to submit for publication.
in patients with end-stage renal impairment, patients
Declaration of interests
with multiple myeloma, who sustained MRD negativity MAD has received honoraria from AbbVie, Amgen, Bristol Myers
for 2 years of lenalidomide maintenance after autologous Squibb (BMS), GSK, Janssen, Karyopharm Therapeutics, Pharmacyclics,
HSCT, had no recorded disease progression at median Pfizer, Sanofi, and Takeda Pharmaceuticals. FB holds consulting roles
follow-up of 19·8 months after the 2-year maintenance for Janssen, AstraZeneca, Attralus, and Prothena; and is part of the
speakers’ bureau for GSK, Janssen, and Sanofi. NL has received
landmark.165 We acknowledge that MRD testing might not institutional research support for clinical trials from Omeros and holds
be done in routine clinical practice in all settings; however, stocks in AbbVie. JM holds consulting roles for Amgen, BMS, Janssen,
we encourage the introduction of MRD testing in the Karyopharm Therapeutics, Sanofi, and Takeda Pharmaceuticals.
management of patients with multiple myeloma, as well SJH holds consulting roles for and has received honoraria from AbbVie,
Amgen, BMS-Celgene, GSK, HaemaLogiX, Janssen, Novartis, Roche-
as in patients with end-stage renal impairment, because it Genetec, Takeda Pharmaceuticals, Sanofi, EUSA Pharma, and Terumo;
is the best predictor of prolonged progression-free and research funding from Amgen, BMS-Celgene, GSK, HaemaLogiX,
survival and overall survival.166,167 Janssen, and Roche-Genetec. EK has received honoraria and research
funding from Amgen, Janssen, GSK, and Pfizer. LG has received
honoraria from BMS-Celgene, Janssen, Takeda Pharmaceuticals, Sanofi,
Recommendations and GSK. AG has received honoraria from Janssen, Amgen, and Sanofi.
Kidney transplantation can be considered in some fit NWCJvdD has received research support from Janssen, Amgen,
patients with end-stage renal impairment and sustained Celgene, Novartis, Cellectis, and BMS, all paid to their institution; and
serves in advisory boards for Janssen, Amgen, Celgene, BMS, Takeda
myeloma control (ie, MRD negativity for 2 years) in
Pharmaceuticals, Roche, Novartis, and Adaptive Biotechnologies.
referral centres (grade D recommendation). KCW has received honoraria from AbbVie, Amgen, Adaptive
Biotechnologies, AstraZeneca, BMS-Celgene, BeiGene, GSK, Janssen,
Conclusions Karyopharm Therapeutics, Novartis, Oncopeptides, Pfizer, Roche,
Sanofi, Stemline Therapeutics, and Takeda Pharmaceuticals; and
The diagnosis and management of renal impairment
research support (paid to their institution) from AbbVie, Amgen,
in patients with multiple myeloma is often challenging BMS-Celgene, GSK, Janssen, and Sanofi. AZB has received research
and requires a multidisciplinary approach. The updated grants from Janssen, BMS, GSK, and Celgene. MB serves in advisory
clinical practice recommendations address the therapeutic boards for Janssen, Takeda Pharmaceuticals, Sanofi, Menarini, and
Pfizer; and is part of the speakers’ bureau for Janssen, Takeda
advances in myeloma and the introduction of new agents
Pharmaceuticals, and Sanofi. JH has received honoraria for serving in
and combinations in the management of patients with advisory boards from Amgen, Angitia, Axxess Network, GSK, Janssen,
multiple myeloma and renal impairment. Several factors and Sanofi; honoraria for talks from Amgen, BeiGene, Beijing Medical
complicate the assessment of outcomes in patients with Award Foundation, Curio Science, Janssen, and Target Oncology; and is
part of the Data Safety Monitoring Committee for Janssen. MM has
multiple myeloma and renal impairment and should be received honoraria from Adaptive Biotechnologies, Amgen, Astellas
addressed in future studies to optimise clinical practice Pharma, BMS, GSK, Janssen, Jazz Pharmaceuticals, Novartis, Pfizer,
and patient outcomes. Limitations in the available studies Sanofi, Stemline Therapeutics, and Takeda Pharmaceuticals; and
pertain to the method of renal impairment definition and research funding from Janssen and Sanofi. PJH is a member of advisory

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 Policy Review

boards (without honorarium) for Antengene, Gilead Science, Janssen, 13 Dimopoulos MA, Delimpasi S, Katodritou E, et al. Significant
and Pfizer. M-VM has received honoraria derived from lectures and improvement in the survival of patients with multiple myeloma
participation in advisory boards from Janssen, BMS-Celgene, Takeda presenting with severe renal impairment after the introduction of
Pharmaceuticals, Amgen, GSK, AbbVie, Pfizer, Regeneron novel agents. Ann Oncol 2014; 25: 195–200.
Pharmaceuticals, Roche, Sanofi, and Oncopeptides. PR holds consulting 14 Uttervall K, Duru AD, Lund J, et al. The use of novel drugs can
roles for Oncopeptides, BMS-Celgene, Karyopharm Therapeutics, effectively improve response, delay relapse and enhance overall
Sanofi, GSK, AstraZeneca, Takeda Pharmaceuticals, and Janssen; and survival in multiple myeloma patients with renal impairment.
PLoS One 2014; 9: e101819.
has received research grants from Oncopeptides, BMS-Celgene,
Karyopharm Therapeutics, and Takeda. JB has received honoraria for 15 van de Donk NWCJ, Richardson PG, Malavasi F. CD38 antibodies
in multiple myeloma: back to the future. Blood 2018; 131: 13–29.
lectures from Janssen, Amgen, BMS-Celgene, and Sanofi. PM has
received honoraria from and serves in advisory boards for Janssen, 16 Dimopoulos MA, Moreau P, Terpos E, et al. Multiple myeloma:
EHA-ESMO clinical practice guidelines for diagnosis, treatment
Celgene, Amgen, Takeda Pharmaceuticals, Sanofi, AbbVie, and GSK.
and follow-up. HemaSphere 2021; 5: e528.
JS-M serves in advisory boards and provides consulting services, on
17 Dimopoulos MA, Sonneveld P, Leung N, et al. International
behalf of their institution, for AbbVie, Amgen, BMS, Celgene, GSK,
Myeloma Working Group recommendations for the diagnosis and
HaemaLogiX, Janssen-Cilag, Karyopharm Therapeutics, MSD, Novartis, management of myeloma-related renal impairment. J Clin Oncol
Pfizer, Takeda Pharmaceuticals, Regeneron Pharmaceuticals, Roche, 2016; 34: 1544–57.
Sanofi, and SecuraBio. SVR is a member of the board of directors for the 18 Atkins D, Best D, Briss PA, et al. Grading quality of evidence and
International Myeloma Foundation and has received royalties for strength of recommendations. BMJ 2004; 328: 1490.
creating content from UpToDate. HL has received honoraria from 19 Terpos E, Zamagni E, Lentzsch S, et al. Treatment of multiple
Celgene, Janssen-Cilag, Takeda Pharmaceuticals, Amgen, BMS, Sanofi, myeloma-related bone disease: recommendations from the Bone
AbbVie, Pfizer, and Seagen; and research support from Amgen and Working Group of the International Myeloma Working Group.
Sanofi. ET has received honoraria from Amgen, AstraZeneca, BMS, Lancet Oncol 2021; 22: e119–30.
EUSA Pharma, GSK, Integris Pharma, Janssen, Pfizer, Sanofi, and 20 Bridoux F, Leung N, Belmouaz M, et al. Management of acute
Takeda Pharmaceuticals; research support (paid to their institution) kidney injury in symptomatic multiple myeloma. Kidney Int 2021;
from Amgen, GSK, Janssen, Sanofi, and Takeda Pharmaceuticals; and 99: 570–80.
travel grants from Amgen, EUSA Pharma, and Takeda Pharmaceuticals. 21 Leung N, Bridoux F, Batuman V, et al. The evaluation of
All other authors declare no competing interests. monoclonal gammopathy of renal significance: a consensus report
of the International Kidney and Monoclonal Gammopathy Research
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E D C D (A A E E D A A0 A / D D , A 2 2 D ) A . EC D E H D A 1 D
E C DE A I E H A 0 E C D A D E E EEA D K LA ) C D E H D A 3 E E D E D E DH E