Biallelic Loss of BCMA As a Resistance Mechanism to CAR T Cell Therapy in a Patient with Multiple Myeloma

Overview

Journal Nat Commun

Specialty Biology

Date 2021 Feb 9

PMID 33558511

Citations 173

Authors

Mehmet Kemal Samur

Mariateresa Fulciniti

Anil Aktas Samur

Abdul Hamid Bazarbachi

Yu-Tzu Tai

Rao Prabhala

Alejandro Alonso

Adam S Sperling

Timothy Campbell

Fabio Petrocca

Kristen Hege

Shari Kaiser

Herve Avet Loiseau

Kenneth C Anderson

Nikhil C Munshi

Affiliations

Soon will be listed here.

Abstract

BCMA targeting chimeric antigen receptor (CAR) T cell therapy has shown deep and durable responses in multiple myeloma. However, relapse following therapy is frequently observed, and mechanisms of resistance remain ill-defined. Here, we perform single cell genomic characterization of longitudinal samples from a patient who relapsed after initial CAR T cell treatment with lack of response to retreatment. We report selection, following initial CAR T cell infusion, of a clone with biallelic loss of BCMA acquired by deletion of one allele and a mutation that creates an early stop codon on the second allele. This loss leads to lack of CAR T cell proliferation following the second infusion and is reflected by lack of soluble BCMA in patient serum. Our analysis suggests the need for careful detection of BCMA gene alterations in multiple myeloma cells from relapse following CAR T cell therapy.

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