Pomalidomide, Bortezomib, and Dexamethasone Versus Bortezomib and Dexamethasone in Relapsed or Refractory Multiple Myeloma: Final Survival and Subgroup Analyses From the OPTIMISMM Trial

Paul Richardson; Meral Beksaç; Albert Oriol; Jindriska Lindsay; Fredrik Schjesvold; Monica Galli; Münci Yağcı; Alessandra Larocca; Katja Weisel; Xin Yu; Cynthia Donahue; Jorge Acosta; Teresa Peluso; Meletios Dimopoulos

doi:10.1111/ejh.14365

Pomalidomide, Bortezomib, and Dexamethasone Versus Bortezomib and Dexamethasone in Relapsed or Refractory Multiple Myeloma: Final Survival and Subgroup Analyses From the OPTIMISMM Trial

Eur J Haematol. 2025 Jan 8. doi: 10.1111/ejh.14365. Online ahead of print.

Authors

Paul Richardson¹, Meral Beksaç², Albert Oriol³, Jindriska Lindsay⁴, Fredrik Schjesvold^{5

6}, Monica Galli⁷, Münci Yağcı⁸, Alessandra Larocca⁹, Katja Weisel¹⁰, Xin Yu¹¹, Cynthia Donahue¹², Jorge Acosta¹³, Teresa Peluso¹³, Meletios Dimopoulos^{14

15}

Affiliations

¹ Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
² Istinye University Ankara Liv Hospital, Ankara, Turkey.
³ Institut Català d'Oncologia and Institut Josep Carreras, Hospital Germans Trias i Pujol, Barcelona, Spain.
⁴ East Kent Hospitals University NHS Foundation Trust, Kent and Canterbury Hospital, Canterbury, UK.
⁵ Oslo Myeloma Center, Department of Hematology, Oslo University Hospital, Oslo, Norway.
⁶ KG Jebsen Center for B Cell Malignancies, University of Oslo, Oslo, Norway.
⁷ Hematology and Bone Marrow Transplant Unit, ASST Papa Giovanni XXIII, Bergamo, Italy.
⁸ Gazi University Medical Facility, Ankara, Turkey.
⁹ Division of Hematology, University of Torino, Torino, Italy.
¹⁰ Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
¹¹ Celgene, a Bristol-Myers Squibb Company, Summit, New Jersey, USA.
¹² Bristol Myers Squibb, Princeton, New Jersey, USA.
¹³ Celgene International Sàrl, a Bristol-Myers Squibb Company, Boudry, Switzerland.
¹⁴ Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
¹⁵ Department of Medicine, Korea University, Seoul, South Korea.

PMID: 39777934
DOI: 10.1111/ejh.14365

Abstract

Introduction: In the OPTIMISMM trial, pomalidomide/bortezomib/dexamethasone (PVd) significantly prolonged median progression-free survival (PFS) versus bortezomib/dexamethasone (Vd) in lenalidomide-exposed relapsed and refractory multiple myeloma (RRMM). We report final overall survival (OS) and updated efficacy analyses.

Methods: Adults with RRMM who had 1-3 prior regimens, including lenalidomide (≥ 2 cycles), were assigned (1:1) to PVd or Vd.

Primary endpoint: PFS. Prespecified secondary endpoint: OS. Prespecified exploratory endpoints: PFS2 and subgroup efficacy analyses.

Results: With an overall event rate of 70.0%, OS data were mature in the intent-to-treat population (N = 559). After median follow-up of 64.5 months (data cutoff: May 13, 2022), median OS was 35.6 months with PVd versus 31.6 months with Vd (HR 0.94, 95% CI 0.77-1.15, p = 0.571); adjusting for subsequent therapies, OS improved with PVd versus Vd (HR 0.76, 95% CI 0.619-0.931, p = 0.008). Median PFS2 was 22.1 versus 16.9 months, respectively (HR 0.77, 95% CI 0.64-0.94, nominal p = 0.008). Treatment-emergent adverse events led to study drug discontinuation in 92 (33.1%) and 53 (19.6%) patients in PVd and Vd arm, respectively.

Conclusions: Findings showed a nonsignificant trend towards improved OS with PVd versus Vd. PFS2 favored PVd, supporting its use in RRMM.

Keywords: OS; phase 3 trial; pomalidomide; relapsed or refractory multiple myeloma.

Grants and funding

Celgene, a Bristol-Myers Squibb company