The standard-of-care for patients with LBCL consists of chemotherapy and additional high intensity chemotherapy followed by stem cell transplantation.
In an interim analysis of the TRANSFORM trial comparing the chimeric antigen receptor (CAR) T-cell therapy lisocabtagene maraleucel (liso-cel) to standard of care found that liso-cel significantly improved event-free survival (EFS) for patients with large B-cell lymphoma (LBCL) that continued or returned within 12 months after treatment with first-line chemotherapy, according to an ASH 2021 press release.
The standard-of-care for patients with LBCL consists of chemotherapy and additional high intensity chemotherapy followed by stem cell transplantation. The trial met its primary endpoint in patients receiving CAR T-cell therapy, who showed a median of 10.1 months without complications or cancer progression, which was a substantial improvement over the median of 2.3 months EFS among those receiving standard of care.
“The current standard of care consisting of chemotherapy and transplant is not effective at curing most patients with high risk relapsed large B-cell lymphoma, representing a huge unmet need in our field,” said Manali Kamdar, MD, of the University of Colorado Cancer Center, in a press release.
Liso-cel is currently approved for the FDA as a third-line treatment for lymphoma patients whose cancer does not respond to 2 prior lines of therapy. The TRANSFORM study was created to assess the treatment’s efficacy against standard of care as a second-line treatment, which would potentially make patients eligible for CAR T-cell therapy sooner and avoid the need to go through stem cell transplantation, according to the study.
“Despite a relatively short follow-up period of just over 6 months, the positive results of this study suggest that CAR T-cell therapy has the potential to become the new standard of care for patients who do not respond to initial chemotherapy or who relapse within 12 months,” Kamdar said in the press release.
The study randomized 184 patients to receive liso-cel or standard of care. All patients had relapsed or refractory LBCL and were eligible to receive a stem cell transplant.
Liso-cel was found to significantly extend the median length of survival without disease progression by 9 months compared to standard of care. The researchers also found that liso-cel increased the likelihood of achieving a complete response to treatment, which occurred in 66% of those receiving liso-cel compared with 39% of those receiving standard of care. Out of the 92 patients randomized to receive standard of care, 50 patients ultimately crossed over to receive liso-cel.
The safety profile was comparable to the standard of care, and some patients were able to receive liso-cel infusion in the outpatient clinic setting. Half of the patients receiving liso-cel experienced cytokine release syndrome and 12% experienced neurological toxicity, with the most common neurological adverse effects being headaches, dizziness, tremors, and problems with speech. However, there were no deaths attributable to liso-cell treatment.
“This is a breakthrough therapy which has shown superiority over standard of care in terms of efficacy with an extremely favorable safety profile. We are excited about the potential of this study to change the existing standard of care in these high-risk patients,” Kamdar said in the press release.
The research team will continue to follow patients to evaluate any differences in overall survival at the time of primary analysis, according to the press release.
Researchers examine opportunities for immune-modulating approaches to improve outcomes and reduce side effects- Transform study reports car t-cell therapy liso-cel significantly improves outcomes for relapsed and refractory large b-cell lymphoma. December 11, 2021. Accessed December 13, 2021. https://www.hematology.org/newsroom/press-releases/2021/new-studies-highlight-how-immunotherapies-are-transforming-care-for-blood-cancers