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Leukemia. 2019 Sep;33(9):2266-2275. doi: 10.1038/s41375-019-0435-7. Epub 2019 Mar 11.

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

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Department of Medicine, Division of Hematology & Oncology, Vanderbilt University Medical Center, Nashville, TN, USA.
Division of Hematology, Mayo Clinic, Rochester, MN, USA.
University of Wisconsin, Madison, WI, USA.
University of Texas Southwestern Medical Center, Dallas, TX, USA.
Department of Hematologic Oncology & Blood Disorders Levine Cancer Institute/Carolinas Health Care, Charlotte, NC, USA.
Stanford Cancer Institute, Stanford, CA, USA.
Division of Hematology/Oncology, University of Alabama at Birmingham, Birmingham, AL, USA.
Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA.
Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
Adult Hematologic Malignancies & Stem Cell Transplant Section, Seidman Cancer Center, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.
Department of Medicine, Division of Hematologic Malignancies and Cellular Therapy, Duke University School of Medicine, Durham, NC, USA.
Oregon Health & Science University, Portland, OR, USA.
University of Vermont, College of Medicine, Burlington, VT, USA.
Division of Hematology/Oncology, University of Alabama at Birmingham, Birmingham, AL, USA.


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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