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. 2023 Dec 1;129(23):3746-3760.
doi: 10.1002/cncr.34987. Epub 2023 Aug 25.

Single-agent belantamab mafodotin in patients with relapsed/refractory multiple myeloma: Final analysis of the DREAMM-2 trial

Ajay K Nooka  1 , Adam D Cohen  2 , Hans C Lee  3 , Ashraf Badros  4 , Attaya Suvannasankha  5 , Natalie Callander  6 , Al-Ola Abdallah  7 , Suzanne Trudel  8 , Ajai Chari  9 , Edward N Libby  10 , Maria Chaudhry  11 , Malin Hultcrantz  12 , K Martin Kortüm  13 , Rakesh Popat  14 , Douglas Sborov  15 , Shawn Hakim  16 , Eric Lewis  17 , Boris Gorsh  16 , Bharat Bhushan  18 , Astrid McKeown  19 , Ira Gupta  17 , Joanna Opalinska  16 , Paul G Richardson  20 , Sagar Lonial  1
Affiliations

Single-agent belantamab mafodotin in patients with relapsed/refractory multiple myeloma: Final analysis of the DREAMM-2 trial

Ajay K Nooka et al. Cancer. .

Abstract

Background: Patients with relapsed/refractory multiple myeloma (RRMM) have a high unmet treatment need. Belantamab mafodotin (belamaf), a first-in-class, B-cell maturation antigen-binding antibody-drug conjugate, eliminates myeloma cells through direct cell killing and an anti-myeloma immune response.

Methods: DREAMM-2 (NCT03525678) was a phase 2, two-arm, open-label trial in patients with heavily pretreated RRMM who had three or more prior therapies, were refractory to an immunomodulatory agent and a proteasome inhibitor, and refractory or intolerant to an anti-CD38 monoclonal antibody. Belamaf was given at 2.5 or 3.4 mg/kg every 3 weeks. The primary end point was overall response rate (ORR); secondary end points included progression-free survival (PFS), overall survival (OS), safety, ocular symptoms, and health-related quality of life (HRQOL).

Results: This final analysis (cutoff date, March 31, 2022), N = 223, with median follow-up of 12.5 and 13.8 months, demonstrated an ORR of 32% and 35%, median PFS of 2.8 and 3.9 months, and median OS of 15.3 and 14.0 months in the 2.5 mg/kg and 3.4 mg/kg cohorts, respectively. Median duration of response was 12.5 and 6.2 months. No new safety signals were observed; the most common Grade 3 and 4 adverse events were keratopathy (29% vs. 25%), thrombocytopenia (22% vs. 29%), and anemia (21% vs. 28%). HRQOL outcomes suggest that overall global health status/quality of life, physical and role functioning, and overall disease symptoms were maintained or improved during treatment.

Conclusions: This final analysis of DREAMM-2 confirms that in patients with triple-class refractory RRMM, single-agent belamaf results in durable and clinically meaningful responses with a manageable safety profile.

Keywords: B-cell maturation antigen; antibody-drug conjugate; clinical activity; monoclonal antibody; multiple myeloma.

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Conflict of interest statement

Ajay K. Nooka reports grant funding and personal fees from GSK, Janssen, Bristol-Myers Squibb, Takeda, Pfizer, Karyopharm, and Amgen, and personal fees from Beyond Springs, Adaptive, SecuraBio, Sanofi, and Oncopeptides. Adam D. Cohen reports grant funding and personal fees from GSK, Janssen, Celgene, Novartis, Amgen, Genentech/Roche, Seagen Inc, and Millenium/Takeda; personal fees from Bristol-Myers Squibb, Karyopharm, Sanofi, AstraZeneca, AbbVie, Pfizer, Oncopeptides, Ichnos, and Arcellx. Hans C. Lee reports consulting fees from Allogene Therapeutics, Bristol-Myers Squibb, Celgene, Genentech, GSK, Karyopharm, Legend Biotech, Monte Rosa Therapeutics, Oncopetides, Pfizer, Sanofi, and Takeda Pharmaceuticals and research funding from Amgen, Bristol-Myers Squibb, Janssen, GSK, Regeneron, and Takeda Pharmaceuticals. Attaya Suvannasankha reports grant funding and personal fees from GSK, Janssen Oncology, and Karyopharm, and grant funding from Bristol-Myers Squibb and Celgene. NC and A-OA have nothing to disclose. Suzanne Trudel reports grant funding and personal fees from Amgen, Celgene, Janssen, and GSK, and personal fees from Takeda, Novartis, Sanofi, and Karyopharm. Ajai Chari reports grant funding and personal fees from Janssen, Celgene, Novartis, Amgen, Seagen Inc, and Millenium/Takeda; personal fees from Bristol-Myers Squibb, Karyopharm, Sanofi, Oncopeptides, and Antengene, and grant funding from Pharmacyclics. Edward N. Libby reports personal fees from AbbVie and Janssen, and research funding from Celgene, Genentech, Amgen, and GSK. Maria Chaudhry reports consulting fees from Sanofi. Malin Hultcrantz reports consulting fees from Curio Science LLC, GSK, and Intellisphere LLC; research funding from Amgen, Daiichi Sankyo, and GSK; and speakers bureau fees from Bristol-Myers Squibb and GSK. K. Martin Kortüm reports grant funding and personal fees from AbbVie, Bristol-Myers Squibb, Celgene, GSK, Pfizer, and Takeda. Paul G. Richardson reports grant funding from Bristol-Myers Squibb, Celgene, Takeda, and Oncopeptides and served on advisory committees for Celgene, Takeda, and Oncopeptides, Amgen, Janssen, Karyopharm, and Sanofi. Rakesh Popat reports grant funding, personal fees and nonfinancial support from Takeda; personal fees and nonfinancial support from Janssen, Celgene, and GSK; and personal fees from AbbVie. Douglas Sborov reports personal fees from Celgene, Janssen, and Amgen. Shawn Hakim holds stock/shares in GSK. Eric Lewis holds stock/shares in GSK. Boris Gorsh holds stock/shares in GSK. Bharat Bhushan holds stock/shares in GSK. Astrid McKeown holds stock/shares in GSK. Joanna Opalinska holds stock/shares in GSK. Ira Gupta holds stock/shares in GSK and Novartis. Sagar Lonial reports grant funding and personal fees from Celgene and Takeda and personal fees from Novartis, Bristol-Myers Squibb, GSK, Amgen, Merck, and Janssen. The other authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Duration of response.
FIGURE 2
FIGURE 2
Progression-free survival (A) overall and by response category in (B) 2.5 mg/kg and (C) 3.4 mg/kg cohorts, and overall survival (D) overall and by response category in (E) 2.5 mg/kg and (F) 3.4 mg/kg cohorts. MR indicates minimal response; NE, not evaluable; SD, stable disease; PD, progressive disease, PR, partial response; VGPR, very good partial response.
FIGURE 3
FIGURE 3
Cumulative incidence and recovery of the first Grade ≥2 event (KVA scale) in the (A) 2.5 mg/kg cohort, (B) 3.4 mg/kg cohort, and (C) lyophilized 3.4 mg/kg cohort. Percentages are based on the safety population (n = 95). Resolution is defined as time from onset of first Grade ≥2 or above corneal events (on the KVA scale) to the first time that corneal event improved to Grade 1 or better. KVA indicates keratopathy and visual acuity.
See this image and copyright information in PMC

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