Faculty Collaboration Database

Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy. Leukemia 2019 Sep;33(9):2266-2275

Date

03/13/2019

Pubmed ID

30858549

Pubmed Central ID

PMC6820050

DOI

10.1038/s41375-019-0435-7

Scopus ID

2-s2.0-85062828886 (requires institutional sign-in at Scopus site)   373 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.

Author List

Gandhi UH, Cornell RF, Lakshman A, Gahvari ZJ, McGehee E, Jagosky MH, Gupta R, Varnado W, Fiala MA, Chhabra S, Malek E, Mansour J, Paul B, Barnstead A, Kodali S, Neppalli A, Liedtke M, Narayana S, Godby KN, Kang Y, Kansagra A, Umyarova E, Scott EC, Hari P, Vij R, Usmani SZ, Callander NS, Kumar SK, Costa LJ

Author

Parameswaran Hari MD Adjunct Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

ADP-ribosyl Cyclase 1
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Antineoplastic Agents, Immunological
Antineoplastic Combined Chemotherapy Protocols
Cohort Studies
Female
Humans
Immunologic Factors
Immunotherapy
Male
Membrane Glycoproteins
Middle Aged
Multiple Myeloma
Proteasome Inhibitors
Young Adult