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 teclistamab-cqyv (Tecvayli) and elranatamab-bcmm (Elrexfio) are both approved in the same indication.

Notably, on April 5, 2024, 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.