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Multiple myeloma gammopathies

Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy


The introduction of CD38-targeting monoclonal antibodies (CD38 MoABs), daratumumab and isatuximab, has significantly impacted the management of patients with multiple myeloma (MM). Outcomes of patients with MM refractory to CD38 MoABs have not been described. We analyzed outcomes of 275 MM patients at 14 academic centers with disease refractory to CD38 MoABs. Median interval between MM diagnosis and refractoriness to CD38 MoAB (T0) was 50.1 months. The median overall survival (OS) from T0 for the entire cohort was 8.6 [95% C.I. 7.5–9.9] months, ranging from 11.2 months for patients not simultaneously refractory to an immunomodulatory (IMiD) agent and a proteasome inhibitor (PI) to 5.6 months for “penta-refractory” patients (refractory to CD38 MoAB, 2 PIs and 2 IMiDs). At least one subsequent treatment regimen was employed after T0 in 249 (90%) patients. Overall response rate to first regimen after T0 was 31% with median progression-free survival (PFS) and OS of 3.4 and 9.3 months, respectively. PFS was best achieved with combinations of carfilzomib and alkylator (median 5.7 months), and daratumumab and IMiD (median 4.5 months). Patients with MM refractory to CD38 MoAB have poor prognosis and this study provides benchmark for new therapies to be tested in this population.

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We are thankful to the Institutional Review Boards and hospital staff at each participating academic center, REDCap IT support at Vanderbilt University Medical Center, and all the patients and their families. This study was not funded commercially.

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Correspondence to Luciano J. Costa.

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EhM: Consultancy and Speakers Bureau (Takeda, Celgene, Amgen, Janssen); BP: Stock and pension plan (Bristol Myer Squibb); AN: Consultancy (Celgene, Amgen); ML: Consultancy (Amgen/Onyx), Honoraria (Amgen/Onyx, Pfizer, Prothena, Takeda), Research Funding (Amgen/Onyx, BlueBirdBio, Celgene, Genentech/Roche, Gilead, Pfizer, Prothena, Takeda), Membership on an entity’s Board of Directors or advisory committees (Caelum, Pfizer, Prothena, Takeda); PH: Consultancy and Research Funding (Amgen, Celgene), Honoraria (Celgene); RV: Honoraria (Celgene, Bristol Myers Squibb, Takeda, Amgen, Janssen, Karyopharma, Jazz), Research Funding (Celgene, Bristol Myers Squibb, Takeda); SU: Consultancy (Abbvie, Amgen, Celgene, Genmab, Merck, MundiPharma, Seattle Genetics), Research Funding (Amgen, BMS, Celgene, Janssen, Merck, Pharmacyclics, Takeda), Membership on an entity’s Board of Directors or advisory committees (Sanofi); ShK: Consultancy (AbbVie, Celgene, Janssen, Kite Pharma, Merck, Takeda); LC: Honoraria (Amgen, Celgene, AbbVie), Research Funding (Amgen, Celgene, Janssen). The remaining authors declare that they have no conflict of interest.

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Gandhi, U.H., Cornell, R.F., Lakshman, A. et al. Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy. Leukemia 33, 2266–2275 (2019).

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