Isatuximab Plus Carfilzomib and Dexamethasone Versus Carfilzomib and Dexamethasone in Patients with Relapsed Multiple Myeloma: IKEMA Subgroup Analysis by Prior Transplantation.

Autor: Martin TG; University of California San Francisco, San Francisco, California. Electronic address: Tom.Martin@ucsf.edu., Capra M; Centro Integrado de Hematologia e Oncologia, Hospital Mãe de Deus, Porto Alegre, Brazil., Mohty M; Hôpital Saint-Antoine, Sorbonne University, Paris, France., Suzuki K; Department of Hematology, Japanese Red Cross Medical Center, Tokyo, Japan., Quach H; Department of Haematology, St Vincent's Hospital, University of Melbourne, Melbourne, Australia., Cavo M; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli', Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università di Bologna, Bologna, Italy., Moreau P; University of Nantes, Nantes, France., Dimopoulos M; Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens School of Medicine, Athens, Greece., Yong K; Department of Haematology, University College Hospital, London, United Kingdom., Tekle C; Sanofi, Oncology, Cambridge, Massachusetts., Foster MC; Sanofi, Global Medical Affairs, Cambridge, Massachusetts., Barnes Y; Sanofi, Cambridge, Massachusetts., Risse ML; Sanofi, Vitry-Sur-Seine, France., Mikhael J; Applied Cancer Research and Drug Discovery, Translational Genomics Research Institute, City of Hope Cancer Center, Phoenix, Arizona.
Jazyk: angličtina
Zdroj: Transplantation and cellular therapy [Transplant Cell Ther] 2023 Feb; Vol. 29 (2), pp. 134.e1-134.e7. Date of Electronic Publication: 2022 Nov 11.
DOI: 10.1016/j.jtct.2022.11.005
Abstrakt: In the era of highly active novel agents for multiple myeloma (MM), the role, ideal timing, and impact of transplantation on further therapy after relapse remains a matter of debate. The impact of prior transplantation on treatment benefit from monoclonal antibodies in patients with relapsed/refractory MM (RRMM) is largely unknown. Few Phase 3 studies of monoclonal antibody combinations with proteasome inhibitors or immunomodulatory agents have reported outcomes according to transplantation status. This subgroup analysis examined efficacy and safety in patients from the Phase 3 IKEMA study with and without previous transplantation. IKEMA (NCT03275285) was a randomized, open-label, multinational, parallel-group Phase 3 study that investigated isatuximab (Isa), an anti-CD38 monoclonal antibody, combined with carfilzomib and dexamethasone (Isa-Kd; experimental group) versus Kd (control group) in 302 patients with RRMM and 1 to 3 prior lines of therapy. Patients were randomized in a 3:2 ratio to either Isa-Kd or Kd, with stratification by number of prior lines (1 versus more than 1) and Revised International Staging System (R-ISS) stage (I or II versus III versus not classified). Treatment was given until progressive disease, unacceptable adverse events, or patient choice. Of the 302 randomized patients in IKEMA, 185 (61.3%) had received a prior transplant, comprising 116 of 179 (64.8%) patients in the Isa-Kd arm and 69 of 123 (56.1%) patients in the Kd arm. After a median follow-up of 20.6 months, median progression-free survival (PFS) in patients with prior transplant was not reached with Isa-Kd versus 19.15 months with Kd (hazard ratio [HR] = 0.60; 99% confidence interval [CI], 0.31-1.16). After a median follow-up of 20.8 months, median PFS in patients without prior transplant was not reached with Isa-Kd versus 18.99 months with Kd (HR = 0.44; 99% CI, 0.18-1.05). The overall response rate in patients with prior transplant was 87.9% (Isa-Kd) versus 85.5% (Kd). More patients in the Isa-Kd arm achieved a complete response or better compared with the Kd arm (43.1% versus 29.0%). The overall response rate in patients without prior transplant was 84.1% (Isa-Kd) versus 79.6% (Kd). More patients in the Isa-Kd arm achieved a complete response or better compared with the Kd arm (33.3% versus 25.9%). The minimal residual disease negativity rate was higher with Isa-Kd versus Kd in patients with (31.9% versus 13.0%) and without prior transplantation (25.4% versus 13.0%). In patients with prior transplant, Grade 3 or higher treatment-emergent adverse events (TEAEs) were more common with Isa-Kd; however, no increases in serious TEAEs or definitive treatment discontinuations were seen versus Kd. Among patients without prior transplant, serious treatment-related TEAEs were similar, and there were fewer TEAEs leading to definitive discontinuation with Isa-Kd. The most common Grade 3 or higher TEAEs in patients with and without prior transplant were hypertension and pneumonia. For patients who underwent prior transplantation, Isa-Kd is an effective treatment option. Overall, these data demonstrate that Isa-Kd represents a standard of care for patients with RRMM, regardless of prior transplant status.
(Copyright © 2022. Published by Elsevier Inc.)
Databáze: MEDLINE
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