Dr Ignatz-Hoover on the Future of CAR T-Cell Therapy and Bispecific Antibodies in R/R Myeloma

James Ignatz-Hoover, MD, PhD, hematologist/oncologist, University Hospitals Seidman Cancer Center, discusses the future of treatment with CAR T-cell therapy and bispecific antibodies in patients with relapsed/refractory multiple myeloma.

The next generation of CAR T-cell therapies is making significant strides in addressing several critical issues that have arisen in the management of multiple myeloma, such as reducing costs and enhancing efficacy, Ignatz-Hoover begins. These advancements are particularly timely given the recent expansion of various drug labels by the FDA, which is adding layers of complexity and interest to myeloma treatment, he explains. Bispecific T-cell engagers are among the promising developments, and several of these agents currently have accelerated FDA approvals for patients with myeloma, Ignatz-Hoover states. However, to transition these agents from provisional to full approval status, it is imperative to gather more comprehensive data on their adverse effect profiles and long-term clinical outcomes, he reports.

There is a burgeoning interest to identify the optimal niches for each of these agents, Ignatz-Hoover continues. Researchers and clinicians are diligently working to determine the best ways to incorporate these novel therapies into existing treatment protocols, he says. Specifically, there is a focus on how teclistamab-cqyv (Tecvayli) and talquetamab-tgvs (Talvey) can be effectively combined with other therapeutic agents, Ignatz-Hoover elucidates. This involves finding the right combinations and determining the most appropriate stages of treatment at which these combinations should be introduced, he notes.

Another critical area of exploration is the concept of response-adjusted therapy, he continues, adding that this approach involves tailoring treatment plans based on a patient’s response to initial therapies. Ignatz-Hoover says this potentially offers a more personalized and effective treatment regimen. Additionally, the possibility of incorporating treatment breaks is being examined, he adds. These breaks could provide patients with periods of respite from continuous treatment, which might improve their overall quality of life without compromising the efficacy of the treatment, Ignatz-Hoover concludes.

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James Ignatz-Hoover, MD, PhD, discusses the future of CAR T-cell therapy and bispecific antibodies in relapsed/refractory multiple myeloma.


Dr Ignatz-Hoover on Sequencing CAR T-Cell Therapy and Bispecific Antibodies in R/R Myeloma

James Ignatz-Hoover, MD, PhD, hematologist/oncologist, University Hospitals Seidman Cancer Center, discusses the sequencing of CAR T-cell therapy and bispecific antibodies in the treatment of patients with relapsed/refractory multiple myeloma.

Ignatz-Hoover notes that both CAR T-cell therapies, ciltacabtagene autoleucel (cilta-cel; Carvykti) and idecabtagene vicleucel (ide-cel; Abecma), have demonstrated deep responses in patients with relapsed/refractory multiple myeloma. Both agents were previously approved by the FDA for the treatment of patients with relapsed/refractory multiple myeloma following 4 or more prior lines of therapy, including a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 monoclonal antibody. Notably, the BCMA-directed bispecific antibodies 

 are both approved in the same indication.

the FDA expanded the indication for cilta-cel

 to include the treatment of adult patients with relapsed/refractory multiple myeloma who have received at least 1 prior line of therapy, including a PI and an IMiD, and who are refractory to lenalidomide (Revlimid). On the same day, 

the FDA expanded the indication of ide-cel

 to include the treatment of adult patients with relapsed/refractory multiple myeloma after 2 or more prior lines of therapy, including an IMiD, PI, and anti-CD38 monoclonal antibody.

When treating a patient in a setting where a CAR T-cell therapy and a bispecific antibody are both approved, Ignatz-Hoover explains that CAR T-cell therapy requires an extended vein-to-vein time to manufacture the product. Development is underway to address the manufacturing time with next-generation CAR T-cell therapies using rapid protocols in an effort reduce vein-to-vein time, he says.

In comparison to CAR T-cell therapy, bispecific antibodies provide an off-the-shelf treatment option for patients who cannot afford to wait for weeks for CAR T-cell manufacturing, Ignatz-Hoover continues. He explains that bispecific antibodies may also be better tolerated and offer a viable alternative for patients who may not tolerate CAR T-cell therapy.

Ignatz-Hoover emphasizes that these treatment modalities exist along a spectrum of options, catering to the diverse needs of older and frailer patients with multiple myeloma.

The sequencing of CAR T-cell therapy and bispecific antibodies is a critical aspect of treatment decision-making for heavily pretreated patients with multiple myeloma, and Ignatz-Hoover concludes by saying that a tailored approach considering patient characteristics and treatment goals is essential in optimizing outcomes in heavily pretreated patients.

James Ignatz-Hoover, MD, PhD discusses sequencing CAR T cell therapies and bispecific agents in treating pretreated patients with multiple myeloma.

James Ignatz-Hoover, MD, PhD, discusses the current arsenal of FDA-approved bispecific antibodies in multiple myeloma.

Dr Ignatz-Hoover on Bispecific Antibodies in the Multiple Myeloma Treatment Armamentarium

James Ignatz-Hoover, MD, PhD, hematologist/oncologist, University Hospitals Seidman Cancer Center, discusses the current arsenal of FDA-approved bispecific antibodies in multiple myeloma, and expands on challenges that arise when selecting between these agents.

The multiple myeloma treatment landscape has expanded significantly with the FDA approvals of the bispecific antibodies 

 (Talvey), Ignatz-Hoover begins. The first 2 B-cell maturation agents target BCMA, while talquetamab targets GPRC5D. These approvals have provided additional options for patients who have received at least 4 prior lines of therapy and are triple-class exposed, having been treated with a proteasome inhibitor, a CD38 inhibitor, and an immunomodulatory agent (iMID), he details.

All 3 agents have received accelerated approvals, have the same FDA indication, and have similar efficacy and safety profiles, Ignatz-Hoover states. Moreover, these agents all produce overall response rates of approximately 60%, with a significant proportion of patients achieving very good partial response or better, he says. Median progression-free survival rates are also comparable across the agents. However, due to the lack of head-to-head comparisons, it is challenging to determine which agent is superior in terms of efficacy, Ignatz-Hoover notes.

Differences in adverse effect (AE) profiles exist among the agents, with talquetamab potentially causing hair, nail, and oral-pharyngeal AEs that are not observed with teclistamab, Ignatz-Hoover continues. Teclistamab may carry a slightly higher risk of infections compared to talquetamab, although both agents are associated with infection risks, he adds.

Selecting the optimal sequencing of these BCMA-targeting agents has become a critical consideration in myeloma treatment, Ignatz-Hoover says. As all 3 agents have received similar FDA indications, treatment decisions may initially be influenced by local practice patterns until more data become available to guide their use in different treatment settings, Ignatz-Hoover concludes. Ongoing research is needed to elucidate the optimal sequencing and long-term efficacy and safety profiles of these agents.

James Ignatz-Hoover, MD, PhD

Articles

Dr Ignatz-Hoover on the Future of CAR T-Cell Therapy and Bispecific Antibodies in R/R Myeloma

Dr Ignatz-Hoover on Sequencing CAR T-Cell Therapy and Bispecific Antibodies in R/R Myeloma

Dr Ignatz-Hoover on Bispecific Antibodies in the Multiple Myeloma Treatment Armamentarium