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

Ujjawal H. Gandhi, Robert F. Cornell, Arjun Lakshman, Zhubin J. Gahvari, Elizabeth McGehee, Megan H. Jagosky, Ridhi Gupta, William Varnado, Mark A. Fiala, Saurabh Chhabra, Ehsan Malek, Joshua Mansour, Barry Paul, Alyssa Barnstead, Saranya Kodali, Amarendra Neppalli, Michaela Liedtke, Swapna Narayana, Kelly N. Godby, Yubin KangAnkit Kansagra, Elvira Umyarova, Emma C. Scott, Parameswaran Hari, Ravi Vij, Saad Z. Usmani, Natalie S. Callander, Shaji K. Kumar, Luciano J. Costa

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2266-2275
Number of pages10
JournalLeukemia
Volume33
Issue number9
DOIs
StatePublished - Sep 1 2019

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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    Gandhi, U. H., Cornell, R. F., Lakshman, A., Gahvari, Z. J., McGehee, E., Jagosky, M. H., Gupta, R., Varnado, W., Fiala, M. A., Chhabra, S., Malek, E., Mansour, J., Paul, B., Barnstead, A., Kodali, S., Neppalli, A., Liedtke, M., Narayana, S., Godby, K. N., ... Costa, L. J. (2019). Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy. Leukemia, 33(9), 2266-2275. https://doi.org/10.1038/s41375-019-0435-7