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Randomized Controlled Trial
. 2021 Nov 15;127(22):4198-4212.
doi: 10.1002/cncr.33809. Epub 2021 Jul 27.

Longer term outcomes with single-agent belantamab mafodotin in patients with relapsed or refractory multiple myeloma: 13-month follow-up from the pivotal DREAMM-2 study

Sagar Lonial  1 , Hans C Lee  2 , Ashraf Badros  3 , Suzanne Trudel  4 , Ajay K Nooka  1 , Ajai Chari  5 , Al-Ola Abdallah  6 , Natalie Callander  7 , Douglas Sborov  8 , Attaya Suvannasankha  9 , Katja Weisel  10 , Peter M Voorhees  11 , Lynsey Womersley  12 , January Baron  13 , Trisha Piontek  13 , Eric Lewis  14 , Joanna Opalinska  13 , Ira Gupta  13 , Adam D Cohen  15
Affiliations
Randomized Controlled Trial

Longer term outcomes with single-agent belantamab mafodotin in patients with relapsed or refractory multiple myeloma: 13-month follow-up from the pivotal DREAMM-2 study

Sagar Lonial et al. Cancer. .

Abstract

Background: On the basis of the DREAMM-2 study (ClinicalTrials.gov identifier NCT03525678), single-agent belantamab mafodotin (belamaf) was approved for patients with relapsed or refractory multiple myeloma (RRMM) who received ≥4 prior therapies, including anti-CD38 therapy. The authors investigated longer term efficacy and safety outcomes in DREAMM-2 after 13 months of follow-up among patients who received belamaf 2.5 mg/kg.

Methods: DREAMM-2 is an ongoing, phase 2, open-label, 2-arm study investigating belamaf (2.5 or 3.4 mg/kg) in patients with RRMM who had disease progression after ≥3 lines of therapy and were refractory to immunomodulatory drugs and proteasome inhibitors and refractory and/or intolerant to an anti-CD38 therapy. The primary outcome was the proportion of patients that achieved an overall response, assessed by an independent review committee.

Results: As of January 31, 2020, 10% of patients still received belamaf 2.5 mg/kg. Thirty-one of 97 patients (32%; 97.5% confidence interval [CI], 21.7%-43.6%) achieved an overall response, and 18 responders achieved a very good partial response or better. Median estimated duration of response, overall survival, and progression-free survival were 11.0 months (95% CI, 4.2 months to not reached), 13.7 months (95% CI, 9.9 months to not reached), and 2.8 months (95% CI, 1.6-3.6 months), respectively. Response and survival outcomes in patients who had high-risk cytogenetics or renal impairment were consistent with outcomes in the overall population. Outcomes were poorer in patients with extramedullary disease. In patients who had a clinical response and prolonged dose delays (>63 days; mainly because of corneal events), 88% maintained or deepened responses during their first prolonged dose delay. Overall, there were no new safety signals during this follow-up.

Conclusions: Extended follow-up confirms sustained clinical activity without new safety signals with belamaf in this heavily pretreated patient population with RRMM.

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

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Conflict of interest statement

Sagar Lonial reports grant funding and personal fees from Celgene and Takeda and personal fees from Novartis, Bristol‐Myers Squibb, GlaxoSmithKline, Amgen, Merck, and Janssen outside the submitted work. Hans C. Lee reports research funding and personal fees from Amgen, Celgene, Janssen, and Takeda; personal fees from Genentech, GlaxoSmithKline, and Sanofi; and research funding from Daiichi Sankyo and Regeneron outside the submitted work. Ashraf Badros reports consulting fees from Amgen outside the submitted work. Suzanne Trudel reports consulting fees from Celgene, Amgen, and GlaxoSmithKline; honoraria from Celgene, Janssen, Takeda, Sanofi, Karyopharm, and Amgen Canada; and research funding from Celgene, Janssen, Amgen, GlaxoSmithKline, and Genentech outside the submitted work. Ajay K. Nooka reports consulting fees from Amgen, Janssen Oncology, Celgene, Spectrum Pharmaceuticals, Bristol‐Myers Squibb, GlaxoSmithKline, Takeda, Oncopeptides, and Karyopharm Therapeutics; personal fees from GlaxoSmithKline; and research funding from Amgen, Janssen Oncology, and Takeda outside the submitted work. Ajai Chari reports consulting fees from Celgene, Novartis, Amgen, Janssen Oncology, Seattle Genetics, Bristol‐Myers Squibb, Karyopharm Therapeutics, Genzyme, Oncopeptides, Takeda, Antengene, GlaxoSmithKline, and Secura Bio; and research funding from Celgene, Novartis, Janssen, Pharmacyclics, Amgen, Seattle Genetics, and Takeda outside the submitted work. Natalie Callander reports research funding from Cellectar outside the submitted work. Douglas Sborov reports consulting fees, honoraria, and personal fees from Janssen outside the submitted work. Attaya Suvannasankha reports consulting fees from GlaxoSmithKline, Janssen, and Karyopharm Therapeutics; research funding from GlaxoSmithKline, Janssen, Bristol‐Myers Squibb, and Celgene; and personal fees from GlaxoSmithKline and Janssen outside the submitted work. Katja Weisel reports consulting fees/honoraria from Amgen, Adaptive, Bristol‐Myers Squibb, Celgene, Janssen, GlaxoSmithKline, Karyopharm, Takeda and Sanofi; and research funding from Amgen, Celgene, Sanofi, and Janssen outside the submitted work. Peter M. Voorhees reports personal fees from Adaptive Biotechnologies, Bristol‐Myers Squibb/Celgene, Janssen, Novartis, Oncopeptides, and TeneoBio outside the submitted work. Linsey Womersley is an employee of GlaxoSmithKline. January Baron, Trisha Piontek, Eric Lewis, and Joanna Opalinska are employees of and hold stock/shares in GlaxoSmithKline. Ira Gupta is an employee of and holds stock/shares in GlaxoSmithKline and Novartis. Adam D. Cohen reports grant funding from GlaxoSmithKline, Bristol‐Myers Squibb, and Novartis; personal fees from Janssen, Takeda, Oncopeptides, Kite Pharma, Genentech/Roche, AstraZeneca, and Seattle Genetics; and personal fees and other support from GlaxoSmithKline and Celgene outside the submitted work. Al‐Ola Abdallah made no disclosures.

Figures

Figure 1
Figure 1
Patient disposition is illustrated. aTwo patients were re‐randomized and counted twice (once per each randomization). An additional independent group of 25 patients was randomized to receive a lyophilized configuration of belantamab mafodotin (belamaf) 3.4 mg/kg and underwent the same assessments and procedures as the main study. This group was analyzed separately from patients who were randomized to receive the frozen solution; as such, the results are not reported here. bPatients who were allocated to receive belamaf 3.4 mg/kg were not included in this analysis and have been reported previously. cPrimary causes of death in the safety population (n = 47) included the disease under study (n = 40), serious adverse event possibly related to study (n = 1; sepsis 16 ), other (n = 3), and unknown cause (n = 3). dA patient would be counted as ongoing with the study if no study conclusion record were included in the disposition data set.
Figure 2
Figure 2
Duration of response in the overall population (PR or better) is illustrated in (A), by duration of clinical benefit (MR or better) in (B), progression‐free survival is illustrated in (C) the overall population and (D) by response category, and overall survival is illustrated in (E) the overall population and (F) by response category. Responses were assessed in the intention‐to‐treat population (including all randomly assigned patients) by an independent review committee according to the International Myeloma Working Group uniform criteria consensus recommendations. Six patients (6%) were not evaluable (NE) for response and were treated as nonresponders. CI indicates confidence interval; MR, minimal response; NR, not reached; PD, progressive disease; PR, partial response; SD, stable disease. Correction added on 7 September 2021, after first online publication: Figure 2 and its legend have been corrected.
Figure 3
Figure 3
The frequency of corneal and vision‐related events in patients treated with belantamab mafodotin (belamaf) 2.5 mg/kg in the DREAMM‐2 trial (n = 95) is illustrated. aClinically meaningful best‐corrected visual acuity (BCVA) change represents a BCVA of Snellen Visual Acuity 20/50 or worse in the better seeing eye. bDiscontinuation included 1 patient with keratopathy, 1 patient with blurred vision, and 1 patient with reduced visual acuity.
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