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Clinical Trial
. 2024 Feb;30(2):543-551.
doi: 10.1038/s41591-023-02703-y. Epub 2024 Jan 4.

Belantamab mafodotin, pomalidomide and dexamethasone in refractory multiple myeloma: a phase 1/2 trial

Suzanne Trudel  1 , Arleigh McCurdy  2 , Martha L Louzada  3 , Stephen Parkin  4 , Darrell White  5 , Michael P Chu  6 , Rami Kotb  7 , Hira Mian  8 , Ibraheem Othman  9 , Jiandong Su  10 , Aniba Khan  10 , Engin Gul  10 , Donna Reece  11
Affiliations
Clinical Trial

Belantamab mafodotin, pomalidomide and dexamethasone in refractory multiple myeloma: a phase 1/2 trial

Suzanne Trudel et al. Nat Med. 2024 Feb.

Abstract

Due to evolving treatment standards for newly diagnosed multiple myeloma, many patients will be triple-class exposed after initial relapses and have poor survival. Novel therapies and combinations are therefore required to improve outcomes. B cell maturation antigen (BCMA)-targeted biologics have emerged as an important new area of therapeutics for relapsed multiple myeloma. The two-part ALGONQUIN trial evaluated various doses and schedules of the anti-BCMA antibody-drug conjugate belantamab mafodotin plus pomalidomide and dexamethasone for patients who are lenalidomide refractory and proteosome inhibitor exposed. The primary endpoints, including evaluating dose-limiting toxicities, establishing the recommended Part 2 dose (RP2D) and overall response rate for patients treated at the RP2D, were met. Secondary efficacy endpoints included progression-free survival and overall survival. Patients treated on study (N = 87) had a median of three previous regimens and 55.2% were triple-class refractory. At the RP2D the most common adverse events were decrease in best-corrected visual acuity (71.1%), keratopathy (65.8%), fatigue (57.9%), infection (47.4%; 7.9% grade ≥3), neutropenia (39.5%) and thrombocytopenia (39.5%). For RP2D patients (n = 38), the overall response rate was 85.3%, ≥very good partial response 75.7% and estimated two-year progression-free survival 52.8% (95% confidence interval, 33.9% to 82.4%), at a median follow-up of 13.9 months. The RP2D schedule was associated with manageable antibody-drug conjugate-associated corneal adverse events and improved tolerability without compromising efficacy. Belantamab mafodotin plus pomalidomide and dexamethasone induced durable responses with promising overall survival in relapsed multiple myeloma, the results of which are yet to be confirmed in the phase 3 DREAMM-8 study. ClinicalTrials.gov Identifier: NCT03715478 .

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Conflict of interest statement

The authors declare the following competing interests: S.T. received grant support from GSK, Bristol Myers Squibb (BMS), Janssen, Pfizer, Amgen, Roche and Genentech; consulting fees from BMS, GSK and Roche; and honoraria from BMS, Janssen, Amgen, Sanofi and Pfizer. A.M. received honoraria from Celgene, Janssen, Amgen, Takeda, Sanofi and GSK. M.L.L. received research support from BMS/Celgene and Janssen; and honoraria from BMS/Celgene, Janssen, Gilead, AbbVie, AstraZeneca and Takeda. S.P. received consultancy honoraria from Janssen, BMS, FORUS and Apotex; study funding from GSK; and funding from BMS. D.W. received honoraria from Amgen, Antengene, BMS, FORUS Therapeutics, GSK, Janssen, Karyopharm, Pfizer, Sanofi and Takeda. M.P.C. received research support from BMS/Celgene and Janssen; and honoraria from BMS/Celgene, Janssen, Gilead, AbbVie, AstraZeneca and Takeda. R.K. received honoraria from Akcea Therapeutics, Amgen, BMS, Janssen, Merck, Sanofi, Celgene, Pfizer and Takeda; received research funding from Merck and Sanofi; and is a current equity holder in the private company Karyopharm. H.M. received advisory fees from Janssen, Takeda, Amgen, Pfizer, BMS, FORUS and Sanofi; received research funding from Janssen; and is supported by the early career award from Hamilton Health Sciences. I.O. participated in advisory boards for and received honoraria from Amgen, BMS, Celgene, FORUS Therapeutics, Janssen, Pfizer, Sanofi-Genzyme and Takeda; and received research funding from Janssen. J.S., A.K. and E.G. are employees of CMRG. D.R. received research funding and honoraria from, and is on the advisory board of, Janssen, BMS and Takeda; received research funding from Millennium Pharmaceuticals; and received honoraria from Amgen, Sanofi and GSK.

Figures

Fig. 1
Fig. 1. CONSORT diagram of the Algonquin study.
Belamaf-Pd, belamaf, pomalidomide and dexamethasone. *12 patients from Part 1 and 26 patients from Part 2.
Fig. 2
Fig. 2. Kaplan–Meier curves for PFS and OS.
a, PFS in RP2D (n = 38) and all treated patients (N = 87). b, OS in RP2D (n = 38) and all treated patients (N = 87). Est., estimated; KM, Kaplan–Meier; NE, not evaluable.
Extended Data Fig. 1
Extended Data Fig. 1. Study design for both the dose exploration and the RP2D parts of the study.
DLT, dose-limiting toxicity; RP2D, recommended Part 2 dose.
Extended Data Fig. 2
Extended Data Fig. 2. PFS for 1.92mg/kg Q4W and 2.5 mg/kg Q4W, Q8W, and Q12w subgroups.
NE, not evaluable; no., number; PFS, progression-free survival.
Extended Data Fig. 3
Extended Data Fig. 3. Forest plot for patients with confirmed responses (N = 81) by patient subgroup.
The vertical bar for overall response rate (ORR) was set at 0.877 which is the point estimator for the entire study cohort. eGFR, estimated glomerular filtration rate; ISS, International Staging System.
See this image and copyright information in PMC

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