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Shaji K. Kumar, MD
Prashant Kapoor, MD, FACP
Shaji K. Kumar, MD
Prashant Kapoor, MD, FACP
Posted: Monday, December 4, 2023
A noteworthy case of high-risk smoldering myeloma, which ultimately responded to chimeric antigen receptor (CAR) T-cell therapy, was described by Jin Lu, MD, of Peking University People’s Hospital, Beijing, China, and colleagues in the Journal of Translational Internal Medicine. The outcome may highlight such a sequential CD19- and B-cell maturation antigen (BCMA)-targeted regimen as a feasible therapeutic option for this precancerous condition.
“Early intervention with CAR T-cell therapy when the immune microenvironment is still relatively normal and clonal plasma cells do not yet have complex mutations may possibly offer an exceptional opportunity to cure multiple myeloma,” the investigators remarked.
A 30-year-old man presented with a low white blood cell count in June 2017; no underlying factors were identified. He exhibited abnormal immunoglobulin G (IgG) and M-protein levels, as well as IgG lambda positivity. A bone marrow analysis revealed abnormal clonal plasma cells. The patient was diagnosed with monoclonal gammopathy of undetermined significance, which ultimately progressed to smoldering multiple myeloma. A high-risk cytogenetic aberration, t(4;14), was documented.
The patient’s desire for curative treatment and exclusion from clinical trials led to a plan for CAR T-cell immunotherapy. Induction therapy with the proteasome inhibitor ixazomib plus dexamethasone was first administered to reduce the tumor load, which resulted in partial remission. The patient subsequently achieved a very good partial response with the addition of the monoclonal antibody daratumumab.
In June 2020, the patient underwent lymphodepletion followed by CD19-targeted CAR T-cell therapy at a total dose of 5 x 106 cells/kg. He experienced a cytokine-release syndrome of grade 1 and was precautionarily administered antibiotics. After 2 weeks, the patient received two doses of anti-BCMA CAR T cells, totaling 1 × 107 cells/kg over a 3-day period; cytokine-release syndrome was not observed. He subsequently achieved measurable residual disease negativity. As of September 2022, the patient felt well and was continuing follow-up.
Disclosure: Dr. Lu reported no conflicts of interest. For full disclosures of the other study authors, visit degruyter.com.
Journal of Translational Internal Medicine
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