Pomalidomide with or without dexamethasone for relapsed/refractory multiple myeloma in Japan: a retrospective analysis by the Kansai Myeloma Forum
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Determinants of the efficacy and safety of pomalidomide (POM) monotherapy or POM plus dexamethasone (DEX) (POM/DEX) for relapsed and refractory multiple myeloma (RRMM) were examined retrospectively in a real-world clinical practice setting in Japan. The subjects were 108 patients registered with the Kansai Myeloma Forum, who were treated with either POM or POM/DEX. Of these, 79 (73%), 73 (68%), and 58 (54%) were resistant to bortezomib (BTZ), lenalidomide (LEN), and both BTZ and LEN, respectively. The median overall survival (OS) was not reached. The median time to treatment failure (TTF) was 4.4 months. The best response was recorded in 96 patients, with a 31% overall response rate (ORR) and a 79% rate of achieving at least stable disease. Number of pre-POM regimens ≥ 5, non-IgG-type M-protein, and time from initial therapy to POM or POM/DEX therapy < 2 years were associated with shorter TTF and OS. Frequent (> 10%) severe adverse events included neutropenia (55.1%), thrombocytopenia (33.7%), anemia (30.6%), febrile neutropenia (12.2%), fatigue (11.2%), and anorexia (10.2%). In conclusion, POM and POM/DEX showed substantial efficacy against RRMM, but new combination therapies with POM are needed to improve efficacy further without causing hematologic toxicities.
KeywordsMultiple myeloma Pomalidomide Efficacy Adverse events
We wish to thank all myeloma patients registered in KMF and all KMF investigators for their scientific support. We also thank Ms. Okuyama R for her assistance to this study.
YMK and JK designed the study. YMK and IY performed the statistical analysis. HK, YK, SF, AN, HS, NU, HU, HY, SK, TM, JI, MM, KO, MI, HK, MK, KW, CS, SN, KI, MH, IM, YK, and ATK provided patient data.
Compliance with ethical standards
Conflict of interest
This work was supported by grants from Celgene Co., Ltd., Takeda Pharmaceutical Co., Ltd., Fujimoto Pharmaceutical Co., Ltd., and Ono Pharmaceutical Co., Ltd.
- 5.Gandhi AK, Kang J, Havens CG, Conklin T, Ning Y, Wu L, et al. Immunomodulatory agents lenalidomide and pomalidomide co-stimulate T cells by inducing degradation of T cell repressors Ikaros and Aiolos via modulation of the E3 ubiquitin ligase complex CRL4(CRBN). Br J Haematol. 2014;164:811–21.CrossRefPubMedGoogle Scholar
- 6.Iida S. Mechanisms of action and resistance for multiple myeloma novel drug treatments. In t J Hematol. 2016;104:271–2.Google Scholar
- 9.San Miguel J, Weisel K, Moreau P, Lacy M, Song K, Delforge M, et al. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013;14:1055–66.CrossRefGoogle Scholar
- 14.Kuroda J, Shimura Y, Ohta K, Tanaka H, Shibayama H, Kosugi S, et al. Limited value of the international staging system for predicting long-term outcome of transplant-ineligible, newly diagnosed, symptomatic multiple myeloma in the era of novel agents. Int J Hematol. 2014;99:441–9.CrossRefPubMedGoogle Scholar
- 26.Dimopoulos MA, Weisel KC, Song KW, Delforge M, Karlin L, Goldschmidt H, et al. Cytogenetics and long-term survival of patients with refractory or relapsed and refractory multiple myeloma treated with pomalidomide and low-dose dexamethasone. Haematologica. 2015;100:1327–33.CrossRefPubMedPubMedCentralGoogle Scholar
- 32.Hanaizi Z, Flores B, Hemmings R, Camarero J, Sancho-Lopez A, Salmonson T, et al. The European medicines agency review of pomalidomide in combination with low-dose dexamethasone for the treatment of adult patients with multiple myeloma: summary of the scientific assessment of the committee for medicinal products for human use. Oncologist. 2015;20:329–34.CrossRefPubMedPubMedCentralGoogle Scholar
- 34.Siegel DS, Schiller GJ, Song KW, Agajanian R, Stockerl-Goldstein K, Kaya H, et al. Pomalidomide + low-dose dexamethasone following second-line lenalidomide-based therapy in relapsed or refractory multiple myeloma: a phase 2 study investigating efficacy and safety. Blood. 2016;128:4497.Google Scholar