Micrograph of a plasmacytoma, the histologic correlate of a number of myeloma. H&E stain. Credit score: Wikipedia/CC BY-SA 3.0
Teclistamab-cqyv is a T-cell-engaging bispecific antibody that targets a number of myeloma cells through the B-cell maturation antigen (BCMA) receptor. It acquired accelerated approval in 2022 for sufferers handled with 4 or extra strains of prior remedy based mostly on outcomes from the Part I/II MajesTEC-1 medical trial.
Nonetheless, the potential advantages of the bispecific immunotherapy in populations not represented within the trial, or within the presence of threat components related to poorer outcomes, stays an vital focus of ongoing medical investigation.
“Teclistamab is an important treatment option for patients with relapsed/refractory multiple myeloma but there is still a lot to learn about how to modify risk factors and optimize the use of teclistamab in clinical practice,” mentioned Beatrice M. Razzo, MD, an assistant professor at Thomas Jefferson College, former hematology-oncology fellow on the College of Pennsylvania, and the lead writer of the real-world examine involving sufferers handled in a consortium of 15 U.S. tutorial medical facilities.
Within the largest examine of its variety to this point, Razzo and her crew retrospectively analyzed knowledge from 509 a number of myeloma sufferers, half of whom had acquired a minimum of six prior remedies.
The findings have been printed in Blood Most cancers Discovery.
Some 89% (453) of those sufferers would have been ineligible for MajesTEC-1, with the most typical causes being prior remedy with one other BCMA-targeting remedy (236 sufferers), cytopenias (189 sufferers), and an ECOG efficiency standing of two or greater (117 sufferers).
General, sufferers on this examine represented a higher-risk inhabitants, with extra frail people and a better prevalence of multidrug refractory illness and cytogenetic abnormalities, in line with Razzo.
The bispecific antibody decreased illness burden by a minimum of half in 53% (270) of the 506 evaluable sufferers, with 45% (228) having a minimum of 90% discount in illness burden (so-called “very good partial response” within the official response standards).
At a median potential follow-up of 10.1 months, half of sufferers remained freed from development for a minimum of 5.8 months and an estimated 61% had been alive at one 12 months. Even with the excessive prevalence of sufferers with high-risk options, there gave the impression to be no improve in adversarial occasion frequency in comparison with their prevalence in MajesTEC-1 and different real-world analyses of the bispecific antibody’s use.
Notably, the 56 sufferers who would have been eligible for MajesTEC-1 had comparable general response charges in contrast with the registration trial inhabitants, 61% and 63%, respectively.
With regard to MajesTEC-1-ineligible sufferers, the bispecific antibody additionally benefited many sufferers beforehand handled with BCMA-targeting CAR T cells or the antibody-drug conjugate belantamab mafodotin (Blenrep). Forty % exhibited “very good partial responses,” together with 43% of the 58 sufferers whose illness had been beforehand handled with the antibody-drug conjugate and 38% of the 104 sufferers whose illness had beforehand been handled with CAR T cells.
Additional analyses revealed that sufferers who underwent prior BCMA-targeting remedy inside 9 months of beginning teclistamab-cqyv exhibited decrease charges of “very good partial responses” and shorter intervals of progression-free survival.
Nonetheless, this therapeutic resistance occurred extra typically within the group lately handled with CAR T cells than in these lately handled with belantamab mafodotin, who responded at a fee akin to BCMA therapy-naïve sufferers.
“These findings in patients with prior BCMA CAR T cell exposure suggest that increased spacing may allow for the recovery of T-cell fitness or the reemergence of BCMA-expressing subclones. Alternatively, a longer interval may simply reflect less aggressive disease biology,” defined Razzo.
Intensive pretreatment bone marrow infiltration by myeloma cells (60% fraction or greater) or oblique markers of excessive illness burden comparable to anemia, thrombocytopenia, or low absolute lymphocyte rely had been additionally considerably related to decrease charges of “very good partial responses” and shorter intervals of progression-free survival.
The examine additionally discovered that elevated baseline ferritin was related to inferior outcomes independently of illness burden.
“Nevertheless, teclistamab-cqyv remains an important treatment option for patients with late-line, relapsed or refractory multiple myeloma, and should be considered even in those with prior BCMA exposure or markers of high disease burden and inflammation,” mentioned Razzo.
“Our results highlight the complex interplay between real-time clinical parameters and baseline disease features in influencing patient outcomes and suggest that the former may be a more reliable indicator of disease biology than the latter in these patients, but there is still a lot to learn,” she added.
To that finish, Razzo and her colleagues are targeted on their ongoing Part II trial investigating limited-duration drug dosing in sufferers with superior a number of myeloma.
Limitations of the examine embrace the nonstandardized nature of the real-world knowledge in addition to the shortage of a centralized impartial overview or adjudication course of for response and toxicity assessments.
Info relating to the dose depth of teclistamab-cqyv given to sufferers was additionally not out there for evaluation.
Extra data:
Beatrice M. Razzo, et al. Actual-World Expertise with Teclistamab for Relapsed/ Refractory A number of Myeloma from the U.S. Myeloma Immunotherapy Consortium, Blood Most cancers Discovery (2025). DOI: 10.1158/2643-3230.BCD-24-0354
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American Affiliation for Most cancers Analysis
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Information present teclistamab can profit many a number of myeloma sufferers who would have been ineligible for pivotal trial (2025, July 9)
retrieved 9 July 2025
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