Adam Sperling, MD, PhD, a physician at the Dana-Farber Cancer Institute, and an instructor in medicine at Harvard Medical School, discusses future research with CAR T-cell therapy in multiple myeloma.

Randomized phase 3 studies of idecabtagene vicleucel (ide-cel; Abecma) and ciltacabtagene autoleucel (cilta-cel) compared with standard-of-care therapies in relapsed/refractory multiple myeloma are ongoing, says Sperling. Although no data are yet available, it is likely that CAR T-cell therapies will outperform standard therapies in this setting, Sperling adds. 

Additionally, CAR T-cell therapy is being evaluated in earlier lines of treatment for patients with multiple myeloma, Sperling says. The products may have utility in high-risk patients who progress following first-line treatment, or as an option after or instead of stem cell transplant, Sperling says. Combination strategies with CAR T-cell therapy are also emerging to determine whether patients can achieve deeper and more durable responses, Sperling explains. 

Finally, ongoing research efforts are focused on understanding and overcoming mechanisms of resistance to CAR T-cell therapy, Sperling says. Dual-targeting CAR T-cell therapies or combination approaches with CAR T-cell therapy and agents, such as gamma secretase inhibitors, may be useful in combatting resistance to CAR T-cell therapy in multiple myeloma, concludes Sperling.

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Adam Sperling, MD, PhD, discusses future research with CAR T-cell therapy in multiple myeloma.  



Dr. Sperling on Future Research With CAR T-Cell Therapy in Multiple Myeloma 

Adam Sperling, MD, PhD, a physician at the Dana-Farber Cancer Institute, and an instructor in medicine at Harvard Medical School, discusses managing CAR T-cell therapy–related toxicities in multiple myeloma.

Managing cytokine release syndrome (CRS) and neurotoxicity is a challenge in multiple myeloma, says Sperling. However, the experience with CAR T-cell therapy in lymphoma and leukemia has yielded insight into how to best manage these toxicities, Sperling explains. Moreover, physician comfort in intervening early for toxicity management will increase with additional experience in utilizing these products, Sperling says. 

Academic centers that have experience with CAR T-cell therapy from participating in clinical trials will most likely be comfortable using these products in the commercial setting, says Sperling. The protocols for managing CAR T-cell therapy–related toxicities that are being built closely resemble the protocols employed on the clinical trials that evaluated the therapies, Sperling adds.

Notably, the CRS and neurotoxicity observed with idecabtagene vicleucel (ide-cel; Abecma) appear to be less significant compared with those observed with CD19-directed CAR T-cell therapies in lymphoma and leukemia, so toxicities may be easier to manage in multiple myeloma, concludes Sperling.

Adam Sperling, MD, PhD, discusses managing CAR T-cell therapy–related toxicities in multiple myeloma.  



Dr. Sperling on Managing CAR T-Cell Therapy–Related Toxicities in Multiple Myeloma 

Adam Sperling, MD, PhD, a physician at the Dana-Farber Cancer Institute, and an instructor in medicine at Harvard Medical School, discusses future research directions with idecabtagene vicleucel (ide-cel; Abecma) for the treatment of patients with multiple myeloma. 

Ongoing studies are examining the use of ide-cel, as well as other CAR T-cell therapies like ciltacabtagene autoleucel, in early lines of therapy, according to Sperling. These studies are being done in patients who have relapsed quickly after their first-line therapy, Sperling notes. These patients are high risk, and are often primary refractory to their first line of therapy or have relapsed within 6 months to 1 year of undergoing autologous stem cell transplantation, Sperling explains. Currently, not enough data exist to determine whether the durability of response will be better if this modality is utilized in earlier lines, but more information is anticipated, Sperling says. 

Additionally, patients who have been treated with ide-cel did not receive any other therapy, which differs from how patients with multiple myeloma are generally treated, Sperling adds; they did not receive continuous treatment or maintenance therapy. However, ongoing trials are examining whether the durability of responses achieved with this approach can be improved if other therapies are given after CAR T-cell therapy, or in combination with this modality, Sperling concludes.

Adam Sperling, MD, PhD, discusses future research directions with idecabtagene vicleucel for the treatment of patients with multiple myeloma. 

Dr. Sperling on Future Research Directions With Ide-Cel in Multiple Myeloma

Adam Sperling, MD, PhD, physician, Dana-Farber Cancer Institute, instructor in medicine, Harvard Medical School, discusses the rationale to evaluate cellular therapy in multiple myeloma.

The disease biology of multiple myeloma has demonstrated clear involvement with the immune system, and immune escape is an important feature of the malignancy, Sperling explains. As such, immune- and cellular-based therapies have been a cornerstone of treatment in this setting, Sperling adds.

In addition, myeloma plasma cells express BCMA almost universally, Sperling says. Moreover, BCMA is not present on normal cells, making it an optimal target for therapies, Sperling concludes.

Adam Sperling, MD, PhD, discusses the rationale to evaluate cellular therapy in multiple myeloma.  



Adam Sperling, MD, PhD

Articles

Dr. Sperling on Future Research With CAR T-Cell Therapy in Multiple Myeloma

Dr. Sperling on Managing CAR T-Cell Therapy–Related Toxicities in Multiple Myeloma

Dr. Sperling on Future Research Directions With Ide-Cel in Multiple Myeloma

Dr. Sperling on the Rationale to Evaluate Cellular Therapy in Multiple Myeloma