Dr. Ramakrishnan on Negative Results of the BELINDA Trial in Non-Hodgkin Lymphoma

Praveen Ramakrishnan, MD, assistant professor, Department of Internal Medicine, UT Southwestern Harold C. Simmons Comprehensive Cancer Center, discusses the negative results from the phase 3 BELINDA trial (NCT03570892) and its effect on the use of CAR T-cell products in aggressive B-cell non-Hodgkin lymphoma (NHL).

The BELINDA trial evaluated the efficacy and safety of tisagenlecleucel (tisa-cel; Kymriah) vs the current standard of care, which was salvage chemotherapy combined with autologous hematopoietic stem cell transplantation. Results showed that tisa-cel did not significantly improve outcomes in patients with relapsed/refractory NHL compared with standard treatment.

There are several potential explanations for these negative results, Ramakrishnan continues. The trial was subject to a delay in CAR T-cell product manufacturing, causing some patients scheduled to receive tisa-cel to experience prolonged wait time. In the interim, these patients were subjected to more chemotherapy, potentially skewing results. Moreover, it is possible that the highest-risk patients were selected out by investigators due to this concern.

Cross-trial comparisons are notoriously difficult to conduct, Ramakrishnan notes. It is unclear if the results from BELINDA indicate that tisa-cel is inferior to other CAR T-cell therapies such as lisocabtagene maraleucel (liso-cel; Breyanzi) and axicabtagene ciloleucel (axi-cel; Yescarta). However, both these therapies are approved for this patient population in the second-line setting, while tisa-cel is only approved for patients in the third-line setting and beyond.