Group Highlights Barriers to CAR T-Cell Referral for DLBCL

Despite the favorable outcomes associated with chimeric antigen receptor (CAR) T-cell therapy in diffuse large B cell lymphoma (DLBCL), a gap remains in who is eligible for the treatment approach and who receives it, highlighted researchers of a new paper in Transplantation and Cellular Therapy.

With CAR T-cell therapy indications now expanding to second line with axicabtagene ciloleucel (Yescarta) and lisocabtagene maraleucel (Breyanzi), the researchers expressed hope that more patients will get access to the treatment. Currently, it’s estimated that only a small portion of the 3000 to 6000 patients with relapsed/refractory DLBCL who are eligible for CAR T-cell therapy will receive the treatment as a result of various barriers, notably barriers to referral.

The researchers emphasized the importance of early referral for CAR T-cell treatment, as patients eligible for the treatment are often in very late stages of disease, and mitigating delays in care has the potential to improve response rates by more than 10%.

“Patient selection for CAR T therapy is complex and requires consideration of prior therapies, overall fitness, existing comorbidities, and organ function. Although the patient selection criteria for CAR T therapy are often guided by the product label and the inclusion/exclusion criteria outlined in the pivotal clinical trials, a multidisciplinary discussion between oncologists and colleagues at local CAR T therapy meetings can supersede borderline inclusion/exclusion criteria,” explained the researchers.

As with all novel classes of drugs, learning curves face oncologists as they get familiar with the data supporting each treatment and which treatment may best suit each individual patient.

Choosing which CAR T-cell product for referral can depend on various factors, including manufacturing time when determining treatment for patients with more high-risk disease. Manufacturing times vary between products, with a median manufacturing time of 16 days for axicabtagene ciloleucel, 23 days for tisagenlecleucel, and based on data from the TRANSCEND trial, 24 days for lisocabtagene maraleucel.

Decisions may also be made based on safety profiles and anticipated adverse effects (AEs) with each product, particularly for patients who have already relapsed on multiple lines of treatment, explained the researchers.

“Axicabtagene ciloleucel, despite showing the highest numerical ORR [overall reseponse rate] in clinical trials, has a higher incidence of CRS [cytokine release syndrome] and grade ≥3 neurotoxicity, which may be suboptimal for patients with a higher AE risk,” they noted. “For example, a recent analysis of data from the US Lymphoma CAR-T Consortium found that patients receiving axicabtagene ciloleucel who experienced grade ≥3 CRS had worse outcomes than those who experienced grade 1-2 CRS. Tisagenlecleucel and lisocabtagene maraleucel are associated with lower incidences of CRS and AEs and may be better tolerated in patients with a heavy disease burden or multiple comorbidities.”

The group also highlighted patient-related barriers to treatment referral, including concerns over the aforementioned AEs and hospitalization, as well as hesitancies about costs, travel distance to treatment centers, and a lack of caregiver support or income. Discussing well-established protocols regarding safety and the benefit/risk profile of CAR T-cell treatment may help mitigate some of these concerns, explained the researchers.

Reference

Hoffmann MS, Hunter BD, Cobb PW, Varela JC, Munoz J. Overcoming barriers to referral for chimeric antigen receptor T cell therapy in patients with relapsed/refractory diffuse large b cell lymphoma. Transplant Cell Ther. 2023;29(7):440-448. doi:10.1016/j.jtct.2023.04.003