Isatuximab plus carfilzomib and dexamethasone versus carfilzomib and dexamethasone in relapsed multiple myeloma patients with renal impairment: IKEMA subgroup analysis

Capra, Marcelo; Martin, Thomas G.; Moreau, Philippe; Baker, Ross; Pour, Luděk; Min, Chang‐Ki; Leleu, Xavier; Mohty, Mohamad; Segura, Marta Reinoso; Turğut, Mehmet; LeBlanc, Richard; Malinge, Laure; Schwab, Sandrine; Dimopoulos, Meletios A.

doi:10.3324/haematol.2021.279229

Cited by 19 publications

(17 citation statements)

References 40 publications

(76 reference statements)

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“…In our case series, we first employed the standardized FLC ratio instead of serum FLC levels to normalize the results, rendering them comparable between studies and laboratories [ 35 ]. Bortezomib- and dexamethasone-based regimens with or without novel anti-CD38 treatments can rapidly reduce tumor burden and improve renal function, as almost one-quarter of MM patients with severe renal impairment can even stop dialysis [ 36 , 37 , 38 ]. The incidence of renal failure in newly diagnosed MM patients was 26.5%, similar to that already reported, and without differences based on the standardized FLC ratio.…”

Section: Discussionmentioning

confidence: 99%

Serum Free Light-Chain Ratio at Diagnosis Is Associated with Early Renal Damage in Multiple Myeloma: A Case Series Real-World Study

et al. 2022

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The serum free light-chain (FLC) ratio is a sensitive tool for the differential diagnosis of plasma cell disorders and is biomarker of multiple myeloma (MM) progression from premalignant conditions. Here, we investigate the potential role of FLC ratio at diagnosis in identifying early renal damage in MM patients and other correlations with clinical, laboratory, and molecular findings. A total of 34 MM patients who had undergone autologous stem cell transplantation were included in this retrospective case series study, and FLC quantification was performed with nephelometric assays. In our study, sFLC ratio was significantly associated with light-chain MM and β-2 microglobulin levels, likely indicating a high disease burden at diagnosis, especially in patients without heavy chain M-protein at serum electrophoresis. Moreover, the sFLC ratio was inversely correlated with glomerular filtration rate, possibly identifying early renal damage in MM patients. Our preliminary results confirm the importance of early sFLC evaluation, especially in patients with the light-chain MM type and low disease burden, to minimize the risk of late renal failure.

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Section: Discussionmentioning

confidence: 99%

Serum Free Light-Chain Ratio at Diagnosis Is Associated with Early Renal Damage in Multiple Myeloma: A Case Series Real-World Study

et al. 2022

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“…More patients in the Isa-Kd group showed reversal of renal impairment and durable renal responses relative to the Kd group. 31 …”

Section: Isatuximab In Relapsed/refractory Multiple Myeloma (Rrmm) ( ...mentioning

confidence: 99%

Isatuximab in the Treatment of Multiple Myeloma: A Review and Comparison With Daratumumab

Shen

2022

Technol Cancer Res Treat

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Multiple myeloma (MM) is a hematologic malignancy characterized by the proliferation of clonal plasma cells. Although advances in treatment have markedly improved survival outcomes for patients with MM, this disease is still considered incurable owing to its high incidence of relapse and refractoriness. Isatuximab is an anti-CD38 monoclonal antibody that can induce apoptosis in myeloma cells through a variety of mechanisms. Many clinical studies have demonstrated the efficacy and efficiency of isatuximab in both relapsed/refractory multiple myeloma (RRMM) and newly diagnosed multiple myeloma, leading to its approval for the treatment of adults with RRMM in combination therapies. In this review, the structure, mechanisms of action, pharmacokinetics, pharmacogenetics, and safety profile of isatuximab in MM are summarized. Additionally, isatuximab is compared with daratumumab in terms of mechanism and efficacy.

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“…Isatuximab is also approved in combination with carfilzomib + dexamethasone for the treatment of patients with RRMM, based on results from the pivotal phase III IKEMA trial ( N = 302). 83 IKEMA allowed enrollment of patients with eGFR as low as 15 mL/min/1.73 m 2 , 83 and a prespecified subgroup analysis 53 examined efficacy, renal response, and safety in patients with RI (defined as eGFR < 60 mL/min/1.73 m 2 ) at the time of the interim analysis. Patients with RI ( n = 43 in the isatuximab + carfilzomib + dexamethasone (Isa-Kd) group and n = 18 in the Kd group) comprised 26.1% and 16.2% of patients in their respective study arms with evaluable eGFR at baseline.…”

Section: Novel Rrmm Treatments For Patients With Rimentioning

confidence: 99%

“…Notably, the presence of RI was not associated with higher rates of grade 3 or higher cardiac failure, which is a known toxicity of carfilzomib. 53 …”

Section: Novel Rrmm Treatments For Patients With Rimentioning

confidence: 99%

“…Phase II data 73 and numerous real-world experiences have indicated that improvement of renal function is possible with daratumumab; however, phase III trials of daratumumab-based regimens have not reported on renal response rates. Phase III trials 52 , 53 of isatuximab-based regimens have provided robust analyses of efficacy, safety, and renal response data for patients with RI. Late-phase data for elotuzumab have not been reported separately for the population of patients with RI.…”

Section: Novel Rrmm Treatments For Patients With Rimentioning

confidence: 99%

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An overview of treatment options for patients with relapsed/refractory multiple myeloma and renal impairment

Dimopoulos

Mıkhael

Terpos

et al. 2022

Therapeutic Advances in Hematology

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Renal impairment (RI) is a relatively common complication of multiple myeloma, which increases in frequency as disease becomes more advanced and recovery of renal function becomes less likely as patients progress through lines of therapy. Clinical trials in the relapsed/refractory multiple myeloma (RRMM) setting have not uniformly included patients with RI or robustly reported their outcomes. Here, we review existing data among patients with RI and RRMM across drug classes (including immunomodulatory agents, proteasome inhibitors, monoclonal antibodies, antibody-drug conjugates, chimeric antigen receptor T-cell therapies, and exportin-1 inhibitor) to provide an improved understanding of available treatment options for this important population. We highlight data from pivotal clinical trials, including data relating to renal response (as defined by the International Myeloma Working Group) and discuss real-world experiences in patients with RI, where applicable. Despite substantial advances in RRMM treatment, the presence of RI remains associated with reduced overall survival. Consistent inclusion of patients with RI, and uniform reporting of their outcomes, should be encouraged in future prospective trials of treatments for RRMM.

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Isatuximab plus carfilzomib and dexamethasone versus carfilzomib and dexamethasone in relapsed multiple myeloma patients with renal impairment: IKEMA subgroup analysis

Cited by 19 publications

References 40 publications

Serum Free Light-Chain Ratio at Diagnosis Is Associated with Early Renal Damage in Multiple Myeloma: A Case Series Real-World Study

Serum Free Light-Chain Ratio at Diagnosis Is Associated with Early Renal Damage in Multiple Myeloma: A Case Series Real-World Study

Isatuximab in the Treatment of Multiple Myeloma: A Review and Comparison With Daratumumab

An overview of treatment options for patients with relapsed/refractory multiple myeloma and renal impairment

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