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James Ignatz-Hoover, MD, PhD, discusses the evolving use of CAR T-cell therapies and bispecific antibodies in multiple myeloma.
The use of idecabtagene vicleucel (ide-cel; Abecma) and ciltacabtagene autoleucel (Carvykti; cilta-cel) in earlier lines of therapy continues to lead to deep responses in patients with relapsed/refractory multiple myeloma. Despite this, the limitations of this drug class continue to impede their widespread implementation and benefit, according to James Ignatz-Hoover, MD, PhD, who added that the next-generation products may mitigate these concerns.
“The next generation of CAR T products are addressing some of those vein-to-vein issues, cost issues, and [seeking to] improve efficacy,” said Ignatz-Hoover, who is a hematologist/oncologist at the University Hospitals Seidman Cancer Center, in Cleveland, Ohio. “Especially given the recent FDA expansion of both ide-cel’s and cilta-cel’s [respective] labels, the myeloma space is becoming more and more interesting and complex each day.” In the meantime, bispecific antibodies offer an alternative, off-the-shelf therapy for patients who require immediate treatment, and are generally better tolerated than CAR T-cell therapies, Ignatz-Hoover noted.
On April 5, 2024, the FDA expanded the indication for cilta-cel to include adult patients with relapsed/refractory multiple myeloma who have received at least 1 prior line of therapy, including a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 monoclonal antibody, and are refractory to lenalidomide (Revlimid).1 This regulatory decision was concurrent with the FDA’s label expansion for ide-cel to include patients with relapsed/refractory multiple myeloma after 2 or more prior lines of therapy.2
In an interview with OncLive®, Ignatz-Hoover discussed the latest advancements in managing multiple myeloma, focusing on bispecific antibodies and CAR-T cell therapy. Specifically, he shed light on the expansion of the later-line treatment arsenal with the approvals of teclistamab-cqyv (Tecvayli), elranatamab-bcmm (Elrexfio), and talquetamab-tgvs (Talvey); the impact of moving ide-cel and cilta-cel into earlier treatment lines; and efforts to overcome practical barriers to achieving benefit with CAR-T cell therapy.
Ignatz-Hoover: The cup runneth over in myeloma. We have agents that target BCMA: those are elranatamab and teclistamab. Then we have talquetamab, which targets GPRC5D. These [have] all [received] accelerated approvals for patients who have previously received 4 lines of therapy and are triple-class exposed. Patients must have received at least 1 PI, 1 CD38 inhibitor and 1 iMID.
Treatment selection is really challenging right now because the FDA indications for these agents are all the same. Their profiles, according to data from the [respective] trials supporting their accelerated approvals, are all very similar. They all are generating an approximately 60% overall response rate, with a significant portion of patients achieving very good partial response or better. The median progression-free survival is very similar amongst these different agents. However, we don’t have head-to-head comparisons, so we can’t say which one is better.
There are some differences potentially in adverse effect [AE] profile that talquetamab has, including hair, nails, and oropharyngeal AEs, that teclistamab doesn’t. In theory, teclistamab has a [bit higher] risk of infection, but they both are associated with infection risks. [Their use] will end up [being decided based on] local practice patterns—at least initially, until we learn a little more about how these specific agents work in different treatment settings.
That’s a very important clinical discussion and an active area of research. How do we sequence these agents? In general, cilta-cel and ide-cel both [induce] wonderfully deep responses in patients who are heavily pretreated. You do need to be ready for an extended vein-to-vein time to perform leukapheresis in your patients, send the cells out to the pharmaceutical company, transduce, expand the cells, and then give them back to your patient. Extended vein-to-vein time is an issue.
[With] next-generation CAR T cells, [we] are trying to change this. A lot of academic centers, including our own, are developing in-house CAR T cells and rapid manufacturing protocols will lower this vein-to-vein time.
However, right now, bispecific antibodies offer an off-the-shelf therapy for a patient who needs therapy [right away] and can’t wait up to 4 to 6 weeks for the CAR T product to come. Bispecific antibodies are also generally well tolerated and are better tolerated than a CAR T-cell therapy. CAR T-cell therapies themselves are better tolerated than autologous transplant. It is all on a spectrum of options that we could be offering older and frailer patients [with multiple myeloma].
1. Carvykti is the first and only BCMA-targeted treatment approved by the US FDA for patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy. News release. Johnson & Johnson. April 5, 2024. Accessed May 24, 2024. https://www.jnj.com/media-center/press-releases/carvykti-is-the-first-and-only-bcma-targeted-treatment-approved-by-the-u-s-fda-for-patients-with-relapsed-or-refractory-multiple-myeloma-who-have-received-at-least-one-prior-line-of-therapy
2. US FDA approves Bristol Myers Squibb and 2seventy bio’s Abecma for triple-class exposed relapsed or refractory multiple myeloma after two prior lines of therapy. News release. Bristol Myers Squibb and 2seventy bio, Inc. April 4, 2024. Accessed May 24, 2024. https://news.bms.com/news/corporate-financial/2024/U.S.-FDA-Approves-Bristol-Myers-Squibb-and-2seventy-bios-Abecma-for-Triple-Class-Exposed-Relapsed-or-Refractory-Multiple-Myeloma-After-Two-Prior-Lines-of-Therapy/default.aspx
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