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Clinical Trial
. 2020 Oct 23;10(10):106.
doi: 10.1038/s41408-020-00369-0.

Single-agent belantamab mafodotin for relapsed/refractory multiple myeloma: analysis of the lyophilised presentation cohort from the pivotal DREAMM-2 study

Paul G Richardson  1 , Hans C Lee  2 , Al-Ola Abdallah  3 , Adam D Cohen  4 , Prashant Kapoor  5 , Peter M Voorhees  6 , Axel Hoos  7 , Karrie Wang  7 , January Baron  7 , Trisha Piontek  7 , Julie Byrne  7 , Scott Richmond  8 , Roxanne C Jewell  9 , Joanna Opalinska  7 , Ira Gupta  7 , Sagar Lonial  10
Affiliations
Clinical Trial

Single-agent belantamab mafodotin for relapsed/refractory multiple myeloma: analysis of the lyophilised presentation cohort from the pivotal DREAMM-2 study

Paul G Richardson et al. Blood Cancer J. .

Abstract

DREAMM-2 (NCT03525678) is an ongoing global, open-label, phase 2 study of single-agent belantamab mafodotin (belamaf; GSK2857916), a B-cell maturation antigen-targeting antibody-drug conjugate, in a frozen-liquid presentation in patients with relapsed/refractory multiple myeloma (RRMM). Alongside the main study, following identical inclusion/exclusion criteria, a separate patient cohort was enrolled to receive belamaf in a lyophilised presentation (3.4 mg/kg, every 3 weeks) until disease progression/unacceptable toxicity. Primary outcome was independent review committee-assessed overall response rate (ORR). Twenty-five patients were enrolled; 24 received ≥1 dose of belamaf. As of 31 January 2020, ORR was 52% (95% CI: 31.3-72.2); 24% of patients achieved very good partial response. Median duration of response was 9.0 months (2.8-not reached [NR]); median progression-free survival was 5.7 months (2.2-9.7); median overall survival was not reached (8.7 months-NR). Most common grade 3/4 adverse events were keratopathy (microcyst-like corneal epithelial changes, a pathological finding seen on eye examination [75%]), thrombocytopenia (21%), anaemia (17%), hypercalcaemia and hypophosphatemia (both 13%), neutropenia and blurred vision (both 8%). Pharmacokinetics supported comparability of frozen-liquid and lyophilised presentations. Single-agent belamaf in a lyophilised presentation (intended for future use) showed a deep and durable clinical response and acceptable safety profile in patients with heavily pre-treated RRMM.

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Conflict of interest statement

P.G.R. has received grant funding and personal fees from Celgene, Takeda, and Oncopeptides, and personal fees from Janssen, Karyopharm and Sanofi. H.C.L. has received grant funding and personal fees from Amgen, Celgene, Janssen, and Takeda; personal fees from GSK and Sanofi, and grant funding from Daiichi Sankyo. A.-O.A. declares no conflict of interest. A.D.C. has received grant funding from GSK, BMS, and Novartis; personal fees from Janssen, Takeda, Oncopeptides, Kite Pharma and Seattle Genetics, and personal fees and other association with GSK and Celgene. P.K. has received grant funding from GSK, Amgen, Sanofi, Takeda, Sorrento and Janssen (to the institution) and served on an advisory board for GSK (for which the institution received an honorarium). P.M.V. has received personal fees from Adaptive Biotechnologies, BMS/Celgene, Janssen, Novartis, Oncopeptides and TeneoBio. A.H., J. Baron, T.P. and J.O. are employees of and hold stocks and shares in GSK. K.W. and S.R. are employees of GSK. J. Byrne is an employee of GSK and holds stocks/shares in GSK, Adaptimmune, and Novartis. I.G. and R.C.J. are employees of GSK and hold stocks/shares in GSK and Novartis. S.L. has received grant funding and personal fees from Celgene and Takeda, and personal fees from Novartis, BMS, GSK, Amgen, Merck and Janssen.

Figures

Fig. 1
Fig. 1. Patient disposition.
a Between June 2018 and January 2019, 293 patients were screened for inclusion in the entire DREAMM-2 study. Between 5 December 2018 and 10 January 2019, 31 patients were screened for inclusion in the lyophilised presentation cohort. b Patients could have more than one reason for exclusion. c Five patients were excluded due to pre-existing corneal disease, as specified in the study protocol. d The remainder of enrolled patients were included in the main DREAMM-2 study previously reported. Two patients in the main study were re-randomised and counted twice (once per each randomisation). e One patient was randomised to the belamaf 3.4 mg/kg lyophilised presentation, but actually received 3.4 mg/kg frozen-liquid presentation as first dose, and never received lyophilised presentation during the study.
Fig. 2
Fig. 2. Time from randomisation to best confirmed response in responders (n = 13).
Abbreviations: PR partial response, VGPR very good partial response. Responses were assessed by an independent review committee according to International Myeloma Working Group criteria. Orange triangles represent patients with study treatment ongoing. Asterisks represent patients with follow-up ongoing. Responses are indicated at the time of the first report of ≥PR, followed by best response, unless the two occurred concurrently.
Fig. 3
Fig. 3. Duration of response (A) and progression-free survival (B) full analysis population.
Responses were assessed by an independent review committee according to International Myeloma Working Group criteria.
See this image and copyright information in PMC

References

    1. Nooka AK, Lonial S. New targets and new agents in high-risk multiple myeloma. Am. Soc. Clin. Oncol. Educ. Book. 2016;36:e431–e441. doi: 10.14694/EDBK_159516. - DOI - PubMed
    1. Gandhi, U. H. et al. Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy. Leukemia.33, 2266–2275 (2019). - PMC - PubMed
    1. Pick M, et al. Daratumumab resistance is frequent in advanced-stage multiple myeloma patients irrespective of CD38 expression and is related to dismal prognosis. Eur. J. Haematol. 2018;100:494–501. doi: 10.1111/ejh.13046. - DOI - PubMed
    1. Neri P, Bahlis NJ, Lonial S. New strategies in multiple myeloma: immunotherapy as a novel approach to treat patients with multiple myeloma. Clin. Cancer Res. 2016;22:5959–5965. doi: 10.1158/1078-0432.CCR-16-0184. - DOI - PubMed
    1. Yong K, et al. Multiple myeloma: patient outcomes in real-world practice. Br. J. Haematol. 2016;175:252–264. doi: 10.1111/bjh.14213. - DOI - PMC - PubMed

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