An interim analysis of the TRANSFORM trial comparing the chimeric antigen receptor (CAR) T-cell immunotherapy lisocabtagene maraleucel to standard of care found that the CAR T-cell therapy significantly improved event-free survival for patients with large B-cell lymphoma that persisted or returned within 12 months after treatment with first-line chemotherapy. These findings were presented by Manali Kamdar, MD, and colleagues at the 2021 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 91).
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 TRANSFORM trial met its primary endpoint in that the patients receiving lisocabtagene maraleucel 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.
Manali Kamdar, MD
“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 Dr. Kamdar, of the University of Colorado Cancer Center.
More About Lisocabtagene Maraleucel
In February 2021, the U.S. Food and Drug Administration approved lisocabtagene maraleucel for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from indolent lymphoma, high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B. The TRANSFORM study was designed to assess its efficacy against standard of care as a second-line treatment for patients with high-risk, transplant-eligible relapsed or refractory aggressive B-cell non-Hodgkin lymphomas, 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 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,” said Dr. Kamdar.
TRANSFORM Trial
Researchers randomly assigned 184 patients to receive lisocabtagene maraleucel 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, lisocabtagene maraleucel was found to significantly extend the median length of survival without disease progression by 9 months compared to standard of care. It also increased the likelihood of achieving a complete response to treatment, which occurred in 66% of those receiving lisocabtagene maraleucel and 39% of those receiving standard of care. Of 92 patients randomly assigned to receive standard of care, 50 patients ultimately crossed over to receive lisocabtagene maraleucel.
KEY POINTS
- Patients receiving lisocabtagene maraleucel 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.
- Lisocabtagene maraleucel was found to significantly extend the median length of survival without disease progression by 9 months compared to standard of care.
- It also increased the likelihood of achieving a complete response to treatment, which occurred in 66% of those receiving lisocabtagene maraleucel and 39% of those receiving standard of care.
The safety profile of lisocabtagene maraleucel was comparable to the standard of care, and some patients were able to receive the immunotherapy infusion in the outpatient clinic setting. Although roughly half of patients receiving lisocabtagene maraleucel experienced cytokine-release syndrome and 12% experienced neurologic toxicity (with the most common neurologic 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 cytokine-release syndrome or neurologic events reported. There were no deaths attributable to lisocabtagene maraleucel 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,” said Dr. Kamdar.
The researchers will continue to follow patients to assess any differences in overall survival at the time of primary analysis.
Disclosure: For full disclosures of the study authors, visit ash.confex.com.
