An interim analysis of the TRANSFORM trial comparing CAR T-cell therapy lisocabtagene maraleucel (liso-cel) to standard of care found that liso-cel significantly improved event-free survival for patients with large B-cell lymphoma that persisted or returned within 12 months after treatment with first line
Standard of care for this patient group consists of salvage chemotherapy and, for responding patients, additional high intensity chemotherapy followed by stem cell transplantation.
The trial met its primary endpoint in that the patients receiving CAR T-cell therapy survived for a median of 10.1 months without complications or cancer progression, a substantial improvement over the median of 2.3 months of event-free survival 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.
The FDA has currently approved liso-cel as a third-line treatment for lymphoma patients whose cancer doesn’t respond to two prior lines of therapy.
The TRANSFORM study was designed to assess its efficacy against standard of care as a second-line treatment, potentially making patients eligible for CAR T-cell therapy sooner and avoiding the need to go through stem cell transplantation.
“Despite a relatively short follow-up period of just over six 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,” said Dr. Kamdar.
Researchers randomised 184 patients to receive liso-cel or standard of care. All participants had relapsed or refractory large B-cell lymphoma and were eligible to receive a stem cell transplant.
In addition to its demonstrated superiority in terms of the trial’s primary endpoint of event-free survival, liso-cel was found to significantly extend the median length of survival without disease progression by nine months compared to standard of care.
Liso-cel also increased the likelihood of achieving a complete response to treatment, which occurred in 66% of those receiving liso-cel and only 39% of those receiving standard of care. Of 92 patients randomised to receive standard of care, 50 patients ultimately crossed over to receive liso-cel.
The safety profile of liso-cel was comparable to the standard of care and some patients were able to receive liso-cel infusion in the outpatient clinic setting.
CAR T-cell therapy can cause side effects such as CRS and neurological toxicity. Although roughly half of patients receiving liso-cel experienced CRS and 12% experienced neurological toxicity (with the most common neurological side effects being headaches, dizziness, tremors, and problems with speech), these CAR T-cell therapy related toxicities were low grade and reversible, with no grade 4 or 5 CRS or neurological events.
There were no deaths attributable to liso- cel treatment.
“This is a breakthrough therapy which has shown superiority over standard of care in terms of efficacy with an extremely favourable safety profile. We are excited about the potential of this study to change the existing standard of care in these high-risk patients,” said Dr. Kamdar.
The researchers will continue to follow patients to assess any differences in overall survival at the time of primary analysis.
Watch the interview with Dr Kamdar here.
Source: American Society of Haematology