Dr Dholaria on the Use of Liso-Cel in Relapsed/Refractory CLL

Bhagirathbhai Dholaria, MBBS, associate professor, medicine, Division of Hematology and Oncology, Vanderbilt University Medical Center, discusses the benefits and limitations of lisocabtagene maraleucel (liso-cel; Breyanzi) for patients with relapsed/refractory chronic lymphocytic leukemia (CLL).

In the phase 1/2 TRANSCEND CLL 004 trial (NCT03331198), patients with relapsed/refractory CLL received cyclophosphamide and fludarabine–based lymphodepletion followed by a single infusion of liso-cel. Patients in this trial were heavily pretreated; all patients had received prior BTK inhibitors, and several patients with a BTK domain mutation had prior exposure to venetoclax (Venclexta), Dholaria says.

Among patients who achieved a complete response with liso-cel, the median progression-free survival (PFS) was not yet reached at a median follow-up of approximately 24 months. The median PFS was approximately 26.9 months among patients who achieved a partial response. The median PFS was approximately 18.0 months in the overall population. The PFS outcomes were similar between patients who had received prior BCL-2 and BTK inhibitors and the overall trial population, Dholaria explains. 

Liso-cel is effective in patients with relapsed/refractory CLL, and may address some traditional factors associated with high-risk disease, including prior exposure to BTK inhibitors or BCL-2 inhibitors, Dholaria notes. However, one drawback to CAR T-cell therapy is the short-term and long-term toxicity profile associated with this agent, Dholaria emphasizes. Since lymphodepletion is necessary for in vivo CAR T cell expansion, CAR T-cell therapy may not be optimal for patients who are older and/or have several comorbidities, according to Dholaria. Furthermore, the risk of developing cytokine release syndrome and neurotoxicity is high during the first few weeks after liso-cel infusion, Dholaria says. Patients may also experience disease relapse after receiving liso-cel, indicating that this agent is not a curative therapy, Dholaria explains. Relapse-prevention strategies need to be further developed for patients who experience initial responses with liso-cel, Dholaria emphasizes.

Another limitation of CAR T-cell therapy is its cost and lack of accessibility, Dholaria notes. CAR T-cell therapy administration is limited to large academic cancer centers, which may prevent patients from receiving this treatment, Dholaria concludes.