A new immunotherapy target emerges in advanced multiple myeloma
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Targeting the B-cell maturation antigen protein has so far proved successful in treatment of relapsed or refractory multiple myeloma, dramatically increasing response rates and extending the time until disease progression.
More years of follow-up are needed to determine the durability of these therapies and whether they provide a functional cure for a proportion of patients, but researchers are not idly waiting to find out.
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Instead, they have moved on to the next challenge: finding new treatment targets to help those whose disease has progressed despite the use of BCMA-directed therapy.
G protein-coupled receptor family C group 5 member (GPRC5D) is highly expressed on malignant myeloid cells but less frequently in normal tissue. The antigen serves as the molecular target of the investigational T-cell engaging bispecific antibody talquetamab (Janssen), the next immunotherapy likely to receive FDA approval for treatment of advanced multiple myeloma, according to Faith E. Davies, MD, director of the clinical myeloma program and Center for Blood Cancers at NYU Langone’s Perlmutter Cancer Center.
Findings from the phase 1/phase 2 MonumenTAL-1 trial, presented at last year’s ASH Annual Meeting and Exposition, showed an ORR of 73.1% and median PFS of 11.9 months (95% CI, 8.4 to not estimable) among 145 patients who received talquetamab at a dose of 0.8 mg/kg subcutaneously every other week. Nearly three-quarters of patients (72%) in that dose group experienced cytokine release syndrome, but researchers observed no grade 4 or grade 5 cases and reported that the treatment had a manageable safety profile.
“The results look incredibly promising,” Davies told Healio | HemOnc Today. “Talquetamab offers both another effective therapy option but also a choice in therapy for patients.”
Choice means increased complexity for physicians looking to navigate the optimal treatment strategy, Davies noted. GPRC5D is also in development as a target for next-generation chimeric antigen receptor T-cell therapies.
“We may have two different treatments with two different targets, or essentially four different types of therapies,” she said. “We will then need to unpack which treatment to give to whom and when.”
Click here to read the cover story, “Immunotherapies ‘offer incredible hope’ in journey toward multiple myeloma cure.”
For more information:
Faith E. Davies, MD, can be reached at faith.davies@nyulangone.org.
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Chari A, et al. Abstract 157. Presented at: ASH Annual Meeting and Exposition; Dec. 10-13, 2022; New Orleans.
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