Meera Mohan, MD, MS, FACP, assistant professor, hematology, medical oncology, Froedtert & The Medical College of Wisconsin, discusses the significance of CAR T-cell therapies and bispecific antibodies in patients with relapsed/refractory multiple myeloma.

CAR T-cell therapies and bispecific antibodies have expanded the treatment arsenal for patients with relapsed/refractory multiple myeloma, Mohan says. On March 26, 2021, the FDA 

approved the CAR T-cell therapy idecabtagene vicleucel (ide-cel; Abecma)

 for use in patients with relapsed/refractory multiple myeloma who had received at least 4 prior lines of therapy. The decision was supported by findings from the phase 2 KarmMMa trial (NCT03361748). On February 28, 2022, the FDA 

approved ciltacabtageneautoleucel (cilta-cel; Carvykti)

 for patients with relapsed/refractory disease who had received at least 4 prior lines of therapy, based on data from the phase 1b/2 CARTITUDE-1 trial (NCT03548207). Additionally, on October 25, 2022, the FDA 

granted accelerated approval to the bispecific antibody teclistamab

 in patients with relapsed/refractory disease who have received at least 4 prior lines of therapy, backed by findings from the phase 1/2 MajesTEC-1 trial (NCT04557098).

Prior to these FDA approvals, an unmet need existed for effective therapies for patients with triple-class refractory multiple myeloma, Mohan emphasizes. CAR T-cell therapies and bispecific antibodies have generated high and often durable response rates in this population, Mohan explains. For example, in KarMMa, ide-cel generated a 73% overall response rate (ORR), with 19.0-month, 10.4-month, and 4.5-month durations of response (DOR) in patients who achieved a complete response (CR) or stringent CR, those who achieved a very good partial response (PR), and those who achieved a best response of PR, respectively. In CARTITUDE-1, cilta-cel elicited an ORR of 97%, with a median DOR that was not yet reached. In MajesTEC-1, the ORR was 63.0% in patients who received teclistamab, and the median DOR was 18.4 months.

These treatment options have revolutionized the treatment of patients with relapsed/refractory multiple myeloma, Mohan concludes.

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Meera Mohan, MD, MS, FACP, discusses the significance of CAR T-cell therapies and bispecific antibodies in patients with relapsed/refractory multiple myeloma.

Dr Mohan on CAR T-cell Therapies and Bispecific Antibodies in R/R Multiple Myeloma

Meera Mohan, MD, MS, FACP, assistant professor, Department of Medicine, Division of Hematology, Medical College of Wisconsin, medical oncologist, Froedtert Hospital, discusses adverse effects (AEs) associated with CAR T-cell therapy in relapsed/refractory multiple myeloma.

Although the emergence of CAR T-cell therapies and bispecific antibodies have provided effective treatment options for heavily pretreated patients with relapsed/refractory multiple myeloma, these treatments are associated with different toxicities vs other agents used in the multiple myeloma space. Steroid-refractory cytokine release syndrome (CRS) and steroid-refractory immune effector cell–associated neurotoxicity (ICANS) are both AEs that could accompany treatment with CAR T-cell therapy, Mohan explains, adding that there is room for improvement in the management of these toxicities.

Moreover, cytopenias are also linked to treatment with CAR T-cell therapy. In the phase 1/2 CARTITUDE-1 trial (NCT03548207), which supported 

the FDA approval of ciltacabtagene autoleucel (cilta-cel; Carvykti) for the treatment of adult patients with relapsed/refractory multiple myeloma

 following 4 or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, grade 3 or 4 hematologic toxicities included neutropenia (95%), anemia (68%), leukopenia (61%), thrombocytopenia (60%), and lymphopenia (50%). Cytopenias negatively affect quality of life for patients and increase health-care burden, Mohan notes.

Hypogammaglobulinemia is an additional AE associated with BCMA-directed CAR T-cell therapy and bispecific antibodies, Mohan continues. This could lead to infections, and intravenous immunoglobulin replacement as a primary prophylaxis could be considered for the management of hypogammaglobulinemia, she adds.

With the emergence of these novel AEs, developing optimal infection monitoring, prophylaxis, and treatment strategies is important in the era of these newer therapies, Mohan concludes.

Meera Mohan, MD, MS, FACP, discusses adverse effects associated with CAR T-cell therapy in relapsed/refractory multiple myeloma.

Dr Mohan on AEs Associated With CAR T-cell Therapy in R/R Myeloma

Meera Mohan, MD, MS, FACP, assistant professor, Department of Medicine, Division of Hematology, Medical College of Wisconsin, medical oncologist, Froedtert Hospital, discusses the toxicities associated with T-cell–directed therapies in relapsed/refractory multiple myeloma.

The emergence of the CAR T-cell therapies and bispecific antibodies have led to improved responses in later lines of treatment for patients with relapsed/refractory multiple myeloma. However, these new therapies have also led to the introduction of novel toxicities for these patients, and these adverse effects (AEs) require specific management, Mohan begins. Some of the primary toxicities associated with T cell–directed therapy are cytokine release syndrome (CRS), immune effector cell–associated neurotoxicity syndrome (ICANS), and other AEs including cytopenias, infections, and hypogammaglobulinemia, Mohan notes.

As these T-cell–directed therapies gain more prevalence in later lines of therapy and are potentially moved into earlier lines of treatment, it is important to understand how these toxicities affect patients, Mohan continues. Since patients with multiple myeloma are generally older, managing these AEs is necessary, given that these patients could be frail or have comorbidities, Mohan expands.

For example, when a patient who is frail and older experiences CRS, it is important act early, even in the event of low-grade toxicity, she says. Tocilizumab (Actemra) could be administered to mitigate the effects of CRS for these patients, Mohan concludes.

Meera Mohan, MD, MS, FACP, discusses the toxicities associated with T-cell–directed therapies in relapsed/refractory multiple myeloma.

Meera Mohan, MD, MS, FACP

Articles

Dr Mohan on CAR T-cell Therapies and Bispecific Antibodies in R/R Multiple Myeloma

Dr Mohan on AEs Associated With CAR T-cell Therapy in R/R Myeloma

Dr Mohan on Toxicities Associated With T-cell–directed Therapy in Myeloma