|The following article features coverage from the European Hematology Association 2020 virtual meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
Progression-free survival (PFS) was significantly improved with addition of isatuximab to the combination of carfilzomib and dexamethasone (Kd) in patients with relapsed/refractory multiple myeloma, according to results of an interim analysis of a phase 3 clinical trial resented at the Virtual Edition of the 25th European Hematology Association (EHA) Annual Congress.1
Although the clinical outcomes of patients with relapsed/refractory multiple myeloma have improved in recent years with the availability of a number of new agents, additional therapeutic approaches are needed since these patients will eventually experience disease progression. Isatuximab, a CD38-directed monoclonal antibody with cytolytic activity, has recently been approved by the U.S. Food and Drug Administration in combination with pomalidomide and dexamethasone for patients with multiple myeloma treated with at least 2 prior lines of therapy.2
In this multicenter, open-label, randomized phase 3 trial (IKEMA; ClinicalTrials.gov Identifier: NCT03275285), patients with relapsed/refractory multiple myeloma who had received 1 to 3 prior lines of therapy were randomly assigned in a 3:2 ratio to treatment with Kd with or without isatuximab, respectively, and stratified according to number of previous treatment lines, as well as revised International Staging System (R-ISS) stage.
The primary study endpoint was PFS, with secondary study endpoints including overall response rate (ORR), rates of complete response (CR), and very good partial response (VGPR), as well as minimal residual disease negativity (MRD) rate, with MRD-negativity defined as no detectable MRD at a detection limit of 10-5 by next-generation sequencing, overall survival (OS), and safety.
Of the 302 patients enrolled in the study at the time of this interim analysis, 179 and 123 patients were assigned to treatment with and without isatuximab, respectively. Baseline patient characteristics for the overall group included a median age of 64 years, R-ISS stage of I and II in approximately one-half and one-third of patients, respectively, and treatment with 1 , 2, and 3 or more previous lines of therapy in approximately 44%, 33%, and 21% of patients, respectively. In addition, 90% patients were previously treated with a proteasome inhibitor, 78% patients had prior exposure to an immunomodulatory agent, and approximately 30% were refractory to lenalidomide at the time of study entry. In addition, approximately one-quarter of patients had disease characterized by high-risk cytogenetics.
At a median follow-up of 20.7 months, median PFS had not been reached in the isatuximab-Kd arm and was 19.15 months in the Kd arm (hazard ratio [HR], 0.531, 99% CI, 0.318-0.889; P =.0007). Furthermore, the benefit of addition of isatuximab on PFS was observed across many patient subgroups including those aged 65 years or more, patients treated with more than 1 prior line of therapy, and those with a history of prior treatment with a proteasome inhibitor or an immunomodulatory agent.
The ORRs in the 2 study arms were similar at 86.6% and 82.9% for those treated with and without isatuximab (P =.19), although the rate of at least VGPR was significantly higher for those in the isatuximab arm (72.6%) vs the placebo arm (56.1%; P =.0011). In addition, more than a 2-fold increase in the MRD negativity rate in the intent-to-treat population was observed for patients treated with isatuximab-Kd (29.6%) compared with Kd (13.0%; P =.0004). Consistent with the improvement in PFS observed for patients treated with triplet versus doublet therapy, patients receiving isatuximab-containing therapy also had a significantly longer median time to next treatment compared with those treated with Kd (HR, 0.566; 95% CI, 0.380-0.841).
Data related to OS were immature at the time of this interim analysis.
Regarding safety, similar frequencies of serious adverse events (AEs; 59.3% vs 57.4%) and fatal treatment-emergent adverse events (TEAEs; 3.4% vs 3.3%) were observed for patients treated with isatuximab-Kd compared with Kd, although grade 3 or higher AEs were more frequently reported for patients treated Kd plus isatuximab compared with Kd alone (76.8% vs 67.2%). While rates of grade 3 or higher thrombocytopenia (29.9% vs 23.0%) and cardiac failure (4.0% vs 4.1%) were similar in the 2 study arms, higher rates of grade 3 or higher neutropenia were observed for patients receiving isatuximab vs not (19.2% vs 7.4%). In addition, infusion reactions were much more common for patients treated with the isatuximab-based regimen (44.6%) vs Kd (3.3%), although the respective rates of grade 3/4 infusion reactions were 0.6% and 0%.
In summarizing the results of the interim analysis of the IKEMA study, Phillipe Moreau, MD, of the department of hematology at the University de Hospital Hotel-Dieu in France, noted that “isatuximab-Kd may represent a new standard-of-care for patients with relapsed multiple myeloma.”
Disclosures: Research funding was provided for this study by Sanofi. For a full list of author disclosures please refer to the reference.
Read more of Cancer Therapy Advisor‘s coverage of the EHA virtual meeting by visiting the conference page.
- Moreau P, Dimopoulos M-A, Mikhael J, et al. Isatuximab plus carfilzomib and dexamethasone vs carfilzomib and dexamethasone in relapsed/refractory multiple myeloma (IKEMA): Interim analysis of a phase 3, randomized, open-label study. Presented at: Virtual Edition of the 25th European Hematology Association (EHA) Annual Congress; June 2020. Abstract LB2603.
- Isatuximab-irfc (Sarclisa) [package insert]. Bridgewater, NJ: sanofi-aventis U.S. LLC; 2020.