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Vol. 42. Issue S1.
Pages 51-52 (October 2020)
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Vol. 42. Issue S1.
Pages 51-52 (October 2020)
PP 30
Open Access
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
Visits
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M. Turgut1,*, P. Moreau2, M. Dimopoulos3, J. Mikhael4, K. Yong5, M. Capra6, T. Facon7, R. Hajek8, I. Spicka9, M. Risse10, G. Asset11, S. Macé10, T. Martin12
1 Ondokuz Mayis University, Samsun, Turkey
2 University Hospital Hôtel-Dieu, Nantes, France
3 The National and Kapodistrian University of Athens, Athens, Greece
4 Translational Genomics Research Institute, City of Hope Cancer Center, Phoenix, United States
5 University College Hospital, London, United Kingdom
6 Hospital Mãe de Deus, Porto Alegre, Brazil
7 Lille University Hospital, Lille, France
8 University Hospital Ostrava, Ostrava, Czech Republic
9 Charles University in Prague, Prague, Czech Republic
10 Sanofi R&D, Vitry/Alfortville, France
11 Sanofi R&D, Chilly-Mazarin, France
12 University of California at San Francisco, San Francisco, United States
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Objective: To demonstrate benefit of adding Isatuximab (Isa) to (Kd) vs. Kd in relapsed/refractory multiple myeloma (RRMM).

Methodology: In this Phase-3 study (NCT03275285), patients with RRMM and 1–3 prior lines of therapy were randomized 3:2 and stratified by number of prior lines and R-ISS to receive Isa-Kd or Kd. Isa-Kd arm received Isa (10mg/kg IV) weekly for 4 weeks, then every 2 weeks. Both arms received K (20mg/m2 days 1–2, 56mg/m2 thereafter) twice-weekly for 3 of 4 weeks, and d (20mg) twice-weekly. Treatment continued until disease progression or unacceptable adverse events (AE). Primary objective: increase in PFS of Isa- Kd vs. Kd, determined by an Independent Response Committee (IRC). Comparison between arms conducted through log-rank testing. Key secondary objectives: overall response rate (ORR), rate of very good partial response (VGPR) or better, complete response (CR) rate, MRD negativity-rate (105 by NGS), and overall survival (OS). Key secondary endpoints tested with a closed test procedure. Safety data included treatment emergent adverse events (TEAE), hematological, and biochemistry results for all patients. Interim efficacy analysis is planned once 65% of total expected PFS events are observed.

Results: 302 patients (Isa-Kd: 179, Kd: 123) were randomized. Median age 64 (33–90) years; R-ISS I, II, III was 25.8%, 59.6%, 7.9% respectively; 44%, 33% and 23% had 1, 2 and ≥3 prior lines respectively; 90% and 78% had prior proteasome inhibitor and IMiD respectively; 24% had high-risk cytogenetics. At a median follow-up of 20.7 months and with 103 PFS events per IRC, median PFS was not reached for Isa-Kd vs. 19.15 months Kd; HR 0.531 (99% CI 0.318–0.889), one-sided p=0.0007. Thus, the pre-specified efficacy boundary (p=0.005) was crossed. PFS benefit was consistent across subgroups. ORR (≥PR) was 86.6% Isa-Kd vs. 82.9% Kd, one-sided p=0.1930. ≥VGPR rate was 72.6% Isa-Kd vs. 56.1% Kd, p=0.0011. CR rate was 39.7% Isa-Kd vs. 27.6% Kd. MRD negativity-rate (10–5) in ITT was 29.6% (53/179) Isa-Kd vs. 13.0% (16/123) Kd, descriptive p=0.0004. OS was immature (events 17.3% Isa-Kd vs. 20.3% Kd). 52.0% Isa-Kd vs. 30.9% Kd pts remain on treatment. Main reasons for treatment discontinuation were disease progression (29.1% Isa-Kd vs. 39.8% Kd) and AEs (8.4% Isa-Kd vs. 13.8% Kd). Grade ≥3 TEAEs were observed in 76.8% Isa-Kd vs. 67.2% Kd. Treatment-emergent SAEs (59.3% vs. 57.4%) and fatal TEAEs were similar in Isa-Kd and Kd (3.4% vs. 3.3%,) and Infusion reactions were reported in 45.8% (0.6% grade 3–4) Isa- Kd and 3.3% (0% grade 3–4) Kd. Grade ≥3 respiratory infections (grouping): 32.2% Isa-Kd vs. 23.8% Kd. Grade ≥3 cardiac failure (grouping): 4.0% Isa-Kd vs. 4.1% Kd. As per lab results, grade 3–4 thrombocytopenia and neutropenia were reported in 29.9% Isa-Kd vs. 23.8% Kd and 19.2% Isa-Kd vs. 7.4% Kd, respectively.

Conclusion: Addition of Isa to Kd provided superior, statistically-significant improvement in PFS with clinically meaningful improvement in depth of response. Isa-Kd was well tolerated with manageable safety and favourable benefit-risk profile, and represents a possible new standard of care treatment in patients with relapsed MM. Data first presented at EHA 2020 virtual meeting, June 11–21st. Study sponsored by Sanofi.

Idiomas
Hematology, Transfusion and Cell Therapy

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