Identifying ASCT-Ineligible Patients Who Could Benefit From CAR T-Cell Treatment

Researchers of a new paper have characterized groups of patients with diffuse large B-cell lymphoma (DLBCL) who may benefit from chimeric antigen receptor (CAR) T-cell therapy despite not being eligible for autologous stem cell transplantation (ASCT), including older patients with more comorbidities.

Both ASCT and CAR T-cell therapy are intensive and potentially curative treatment options for patients with DLBCL. With a growing amount of real-world data, there have been suggestions that CAR T-cell therapy—currently approved for use after 2 lines of therapy in this setting—may be superior to ASCT in the second line for patients with relapsed or refractory disease. Data also suggest that the technology may be an option for patients who are not eligible for ASCT based on certain patient characteristics, prior treatments, stem cell availability, or tumor chemosensitivity.

“Real-world experience has shown that CAR T-cell therapy is feasible in patients who would not have been eligible for an ASCT. Thus, it is important to identify this ‘subtle but real’ population of patients who are ASCT ineligible but CAR T-cell eligible,” wrote the researchers. “This population of patients will be further defined as we get more experience with CAR T-cell therapy. In particular, it will be important to improve our knowledge regarding treatment-related morbidity and mortality and, if possible, to develop scores capable of predicting the risk of severe/lethal toxicities (acute and delayed) after CAR T cells.”

Their findings were published in European Journal of Cancer.

There are currently 3 ongoing prospective trials—ALYCANTE, TRANSCEND-PILOT-017006, and DALY 2-EU—assessing CAR T-cell treatment in the second line for patients not eligible for ASCT. The researchers of the current study highlighted the importance of identifying such patients to promote optimal use of CAR T-cell treatments.

For example, ASCT is typically offered in younger patients with fewer comorbidities, while CAR T-cell treatment has emerged as a safe option in less fit patients and those who are older. Typically, patients older than 65 to 75 years and patients with intermediate performance status, mild organ dysfunction, or mild comorbidities are not eligible for transplant. However, real-world data have suggested that CAR T-cell therapy may be an option. The group noted that although each institution has its own definition of eligibility for both treatment approaches, eligibility is typically more flexible for CAR T-cell treatment.

The researchers also cited prior treatment as a consideration. While a patient who previously received ASCT would not be eligible for the procedure again, they would be eligible for CAR T-cell therapy.

Another example outlined by the researchers is in the case that stem cell collection was not successful, thus inhibiting the ability for a transplant but still allowing for feasible CAR T-cell treatment. According to the researchers, in these patients, there is a more than 95% success rate in leukapheresis and CAR T-cell manufacturing.

Chemosensitivity is also a consideration, as patients who are refractory to salvage chemotherapy would not benefit from high-dose chemotherapy followed by ASCT. However, due to the unlikelihood of cross resistance, immunotherapy treatment with CAR T cells would be viable.

Reference

Vic S, Lemoine J, Armand P, Lemonnier F, Houot R. Transplant-ineligible but chimeric antigen receptor T- cells eligible: a real and relevant population. Eur J Cancer. Published online September 24, 2022. doi:10.1016/j.ejca.2022.08.019