Sign Up Now!
To sign up for our newsletter or print publications, please enter your contact information below.
First Name *
Last Name *
Email Address (Verify) *
We will request your mailing address on the next page.
We will request your mailing address on the next page.

Depth of Response of Isatuximab + Carfilzomib and Dexamethasone in Relapsed Multiple Myeloma: IKEMA Interim Analysis

Conference Correspondent  - ASH Highlights

The objective of the IKEMA study was to compare isatuximab (Isa), an approved anti-CD38 immunoglobulin (Ig)G kappa monoclonal antibody, plus carfilzomib (K) and dexamethasone (d; Isa-Kd) with Kd via analysis of depth of response, long-term outcomes, and kinetics of tumor response.

The IKEMA study was a randomized, open-label, multicenter phase 3 clinical trial among patients with relapsed multiple myeloma who had received 1 to 3 lines of therapy. The primary end point was progression-free survival (PFS). Secondary end points included overall response rate, very good partial response or better (≥VGPR), and complete response (CR) rate. Primary and secondary end points were determined by an independent review committee. Minimal residual disease (MRD) was assessed in bone marrow aspirates from patients with ≥VGPR. To overcome the interference with Isa in standard immunofixation assay, measurement by mass spectrometry of serum M protein was performed. Cox proportional hazards model was used to estimate hazard ratios (HRs) and corresponding confidence intervals (CIs). Cochran-Mantel-Haenszel test was used to compare treatment arms for secondary end points. All randomized patients not achieving MRD-negative status and those without MRD assessment were analyzed as MRD positive per intention-to-treat (ITT).

A total of 302 patients were randomized (Isa-Kd, n = 179; Kd, n = 123). Deeper responses were observed in patients treated with Isa-Kd versus Kd at a median follow-up of 20.7 months (≥VGPR, 72.6% vs 56.1% [nominal P = .011]; ≥CR, 39.7% vs 27.6%, respectively). MRD-negative status was achieved in 30% of patients in the Isa-Kd arm compared with 13% of patients in the Kd arm (ITT population; nominal P = .0004). The percentage of patients reaching both CR and MRD-negative status was 20.1% in the Isa-Kd arm and 10.6% in the Kd arm. For PFS, HRs favor Isa-Kd versus Kd in both MRD-negative patients (HR, 0.578; 95% CI, 0.052-6.405) and MRD-positive patients (HR, 0.670; 95% CI, 0.452-0.993). Overall, PFS was longer for MRD-negative patients than for MRD-positive patients. Potential to reach MRD-negativity with Isa-Kd is independent of adverse prognostic characteristics, including renal impairment, International Staging System stage 3 at diagnosis, and presence of gain(1q21).

Overall, response to treatment was observed relatively quickly. Among responders, median days to first response were 32.0 versus 33.0; best response, 120.0 versus 104.5; first CR, 184.0 versus 229.5; and first ≥VGPR, 88.0 versus 90.0 for the Isa-Kd and Kd arms, respectively. In addition, quality of life as measured by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-C30 Global Health Status scores was maintained with Isa-Kd.

To examine the interference of Isa with M protein, samples from 27 patients in the Isa-Kd arm with near-CR (only serum immunofixation [IF]-positive IgG kappa) or potential CR (serum remaining M protein ≤0.5 g/dL with IF-positive IgG kappa) were tested by mass spectrometry. In this sample, 11 patients with near CR or potential CR had documented bone marrow plasma cell abundance of <5% and were mass spectrometry negative. Among these 11 patients, 7 were also MRD negative. These results suggest that the current CR rate (irrespective of MRD status) and MRD-negative CR rate in this study are both underestimated, with a potential adjusted CR rate of 45.8% and potential adjusted MRD-negative CR rate of 24%.

In conclusion, treatment with Isa-Kd resulted in a clinically meaningful improvement in depth of response compared with Kd. Based on subsequent analysis, it is likely that the CR rate of 39.7% in the Isa-Kd arm was underestimated as a result of interference of Isa with M protein, and that CR could be reached in 45.8% of these patients. Significantly more patients reached MRD-negativity and CR MRD-negativity with Isa-Kd versus Kd. In both arms, achieving MRD-negative status was associated with longer PFS.


Reference

Abstract 414. ASH 2020. December 6, 2020. Depth of Response and Response Kinetics of Isatuximab Plus Carfilzomib and Dexamethasone in Relapsed Multiple Myeloma: IKEMA Interim Analysis.

Related Items
Pevonedistat plus Azacitidine Improves Outcomes versus Azacitidine Monotherapy in High-Risk MDS
JHOP - February 2021 Vol 11, No 1 published on February 22, 2021 in ASH Highlights, Myelodysplastic Syndromes
Ruxolitinib in Graft-versus-Host Disease: Practice-Changing Results
JHOP - February 2021 Vol 11, No 1 published on February 22, 2021 in ASH Highlights, Graft-versus-Host-Disease
Step-Up Glofitamab Dosing Induces High Response Rates in Relapsed or Refractory Non-Hodgkin Lymphoma
JHOP - February 2021 Vol 11, No 1 published on February 22, 2021 in ASH Highlights, Clinical Trials, Lymphoma
ZUMA-12: Axicabtagene Ciloleucel Shows Substantial Benefit in High-Risk Large B-Cell Lymphoma
JHOP - February 2021 Vol 11, No 1 published on February 22, 2021 in ASH Highlights, CAR T-Cell Therapy, Lymphoma
Momelotinib, a Novel JAK Inhibitor, Makes Inroads in Intermediate- or High-Risk Myelofibrosis
JHOP - February 2021 Vol 11, No 1 published on February 22, 2021 in ASH Highlights, Myelofibrosis, Novel Pharmaceuticals
Oral Vodobatinib Elicits Durable Responses in Heavily Pretreated Patients with Chronic Myeloid Leukemia
JHOP - February 2021 Vol 11, No 1 published on February 22, 2021 in ASH Highlights, Leukemia, Novel Pharmaceuticals
A Phase 2 Study of Isatuximab for Patients with Previously Treated AL Amyloidosis
Conference Correspondent  published on December 9, 2020 in ASH Highlights
VRD Consolidation Followed by Lenalidomide Maintenance versus Maintenance Alone in Transplant-Eligible Patients with NDMM
Conference Correspondent  published on December 9, 2020 in ASH Highlights
A Dose-Finding Study of Belantamab Mafodotin in Combination with Pomalidomide and Dexamethasone for RRMM
Conference Correspondent  published on December 9, 2020 in ASH Highlights
Phase 2 GRIFFIN Study Update: Daratumumab + Lenalidomide, Bortezomib, and Dexamethasone in Transplant-Eligible NDMM
Conference Correspondent  published on December 9, 2020 in ASH Highlights
Copyright © Green Hill Healthcare Communications, LLC. All rights reserved.