CAR T-cell immunotherapy improved progression-free and overall survival in patients with relapsed or refractory marginal zone lymphoma, according to a recent clinical trial published in The Lancet.
Marginal zone lymphoma (MZL) is a group of rare and slow-growing non-Hodgkin lymphomas that develop from B-cells and then spread into lymphoid tissues, including lymph nodes, as well as stomach tissue and bone marrow.
For many patients, symptoms may not appear for years and will not require immediate treatment. While rare, some patients may develop a more aggressive disease trajectory and, despite treatment — which can include chemotherapy, immunotherapy, or targeted treatments — may also relapse. Effective treatment options for these patients are limited.
“Historically, patients with MZL who have had one to two treatments in the past struggle with maintaining a long-term response with subsequent therapies. We expect diminishing returns with each treatment. This is a population that has been routinely marginalized and not well studied in the setting of a clinical trial; therefore, innovations and new treatments in this group have been slow to develop,” said Reem Karmali, MD, MS, associate professor of Medicine in the Division of Hematology and Oncology and a co-author of the study.
The current study investigated the effect of lisocabtagene maraleucel (liso-cel), a chimeric antigen receptor (CAR) T-cell therapy, in 67 patients with relapsed or refractory MZL who had at least two previous lines of therapy. Liso-cel works by targeting a protein on the surface of the lymphoma cell, which then activates re-engineered T-cells to target and kill lymphoma cells.
Patients were enrolled at 30 sites across the U.S., Canada, Europe and Japan, and received a single dose of liso-cel two to seven days following lymphodepleting chemotherapy.
Overall, patients who received liso-cel demonstrated high response rates with sustained disease control at two years, with a 24-month duration of response rate of 89 percent. Two-year progression-free survival and overall survival were also 86 percent and 90 percent, respectively.
Patient reported outcomes after liso-cel treatment also showed noticeable improvements, especially symptom relief, enhanced functioning and improved quality of life.
“These results far supersede results seen with any other therapeutic evaluated in the relapsed/refractory MZL population,” said Karmali, also a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. “With these findings, liso-cel received FDA approval for the management of MZL in the 3l+ setting and is now available to patients, which is a huge breakthrough.”
Next steps, according to Karmali, include determining the efficacy and safety of using liso-cel earlier in MZL treatment.
“Even in third line, it still produces better results than what we see with currently available treatments used in second line, underscoring the importance of considering liso-cel earlier,” Karmali said. “There are also other treatments that are being explored in relapsed or refractory MZL that look very promising, including bispecific antibodies. We hope to have a number of other options for treatment of relapsed or refractory MZL in the near future.”
This work was supported by Celgene, a Bristol-Myers Squibb Company.
