The Race Against Time: Why CAR T-Cell Therapy Isn't a Quick Fix

In an interview with Targeted Oncology, Binod Dhakal, MD, MS, associate professor of medicine in the Division of Hematology at the Medical College of Wisconsin, discusses the rationale behind a study investigating the sequential targeting in multiple myeloma and bridging therapy before CAR T-cell therapy.

BCMA-directed CAR T-cell therapies like ciltacabtagene autoleucel (cilta-cel; Carvykti) and idecabtagene vicleucel (ide-cel; Abecma) have revolutionized the treatment of relapsed/refractory multiple myeloma (RRMM).

Initially, the approvals of cilta-cel and ide-cel were for patients with more than 4 prior lines of therapy. However, their indications have expanded, with earlier approval for cilta-cel in patients with 2 prior lines of therapy and for ide-cel in those with 3 prior lines of therapy. These therapies have significantly improved the outlook for patients with RRMM.

However, significant challenges, particularly the lengthy manufacturing and wait times of up to 6 to 8 put rapidly progressing patients at high risk of disease progression or death, with up to 10% not making it to CAR T. Furthermore, patients with a high disease burden or rapidly relapsing disease who do receive CAR T-cell therapy often experience worse outcomes and increased toxicity. Another challenge is that many late-relapse patients have already received most conventional drugs, limiting effective bridging options to control the disease before CAR T-cell infusion.

Effective bridging strategies are needed to control the disease burden, stabilize the patient's condition, and ensure they are well enough to receive CAR T-cell therapy, especially for those with aggressive or heavily pretreated disease.

It is very important for bridging therapies to target a different antigen than BCMA if a BCMA-directed CAR T-cell therapy is planned. Data suggest that using a BCMA-targeting agent beforeCAR T-cell therapy can negatively impact the outcome of the subsequent BCMA CAR T-cell therapy. To maintain the effectiveness of CAR T, the bridging treatment should target a different antigen to reduce disease burden without affecting the BCMA antigen targeted by the main CAR T-cell therapy.