Multiple myeloma, gammopathies

Pomalidomide–dexamethasone in refractory multiple myeloma: long-term follow-up of a multi-cohort phase II clinical trial

Abstract

Despite therapeutic advances, multiple myeloma remains incurable, with limited options for patients with refractory disease. We conducted a large, multi-cohort clinical trial testing various doses and treatment schedules of pomalidomide and dexamethasone (Pom/dex) in patients with refractory multiple myeloma. Overall, 345 patients were enrolled to six cohorts based on number and type of prior lines of therapy, pomalidomide dose and schedule. Median prior lines of therapy were three with near universal prior exposure to proteasome inhibitors and/or immunomodulatory drugs. A confirmed response rate of 35% was noted for all cohorts (range 23–65%) with higher responses in cohorts with fewer prior lines of therapy. Median time to confirmed response was 2 months and the longest progression-free survival and overall survival seen in any cohort were 13.1 and 47.9 months, respectively. Observed adverse reactions were as expected, with myelosuppression and fatigue being the most common hematologic and non-hematologic adverse events (AEs), respectively. Longer durations of treatment and response, higher response rates and fewer AEs were noted with the 2 mg pomalidomide dose. This is the longest follow-up data for Pom/dex in refractory multiple myeloma and will help shape the real-world utilization of this regimen.

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Acknowledgements

Author contributions

BRL, SK, SVR and MQL designed the clinical trial; SA, JRM, SK, VR, DD, PLB, FKB, SVR, RF, MAG, PK, TS, SRH, AKS, AD, WIG, CBR, YL, RSG, NL, TK, JAL, SJR, AAC-K and MQL conducted the clinical trial; BRL and KML performed the analysis; SA, BRL, KML and MQL wrote the manuscript; and all authors revised and approved the final version of the manuscript.

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Correspondence to M Q Lacy.

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Competing interests

SA has served on advisory board for Amgen, Novartis, Takeda and Pharmacyclics, and receives research funding from Pharmacyclics; JRM receives research funding from Abbvie, Celgene and Sanofi; SK receives research funding from Takeda, Celgene, Novartis, Abbvie, Janssen and Roche; DD receives research funding from Karyopharm, Amgen and Takeda; PLB receives research funding from Novartis, Constellation and Mundipharma, and has served on advisory board for Incyte, Janssen, Adaptive Bioscience and Juno Therapeutics; MAG receives research funding from Celgene, Janssen, Prothena, Ionis, Alnylam and Sandoz; PK has served on advisory board for Sanofi-Genzyme and receives research funding from Takeda, Celgene and Amgen; AKS receives research funding from Celgene, Amgen, Bristol Myers Squibb and Janssen; AD receives research funding from Celgene, Millennium, Pfizer and Janssen, and has received travel grant from Pfizer and Prothena; CBR receives research funding from Celgene, Novartis, Takeda and BMS; YL receives research funding from Janssen; ACK receives research funding from Pharmacyclics; MQL receives research funding from Celgene. The remaining authors declare no conflict of interest. Funding from CA 186781 was utilized to support investigator effort in data analysis and manuscript preparation for this trial.

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Supplementary Information accompanies this paper on the Leukemia website

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