A systematic review and meta-analysis published in Frontiers in Immunology indicates that CAR T-cell therapy is both efficacious and has manageable adverse effects in patients with relapsed or refractory mantle cell lymphoma (MCL). The pooled data from 16 clinical trials and real-world studies, encompassing 984 evaluable patients, showed promising outcomes, particularly in patients who have failed multiple prior lines of therapy.
The meta-analysis, led by Dr. Haixiang Wan from Jiangxi Medical College, provides a comprehensive overview of CAR T-cell therapy's impact on MCL, a challenging hematologic malignancy. The study included data collected up to July 4, 2024, from databases such as PubMed, Embase, and ClinicalTrials.gov.
Efficacy Outcomes
The analysis revealed an estimated overall response rate (ORR) of 89% (95% CI, 87%-91%) and a complete remission (CR) rate of 74% (95% CI, 69%-79%). Progression-free survival (PFS) rates at 6 and 12 months were 68% (95% CI, 59%-76%) and 51% (95% CI, 42%-60%), respectively. Overall survival (OS) rates at 6 and 12 months were 80% (95% CI, 72%-87%) and 69% (95% CI, 54%-82%), respectively.
Safety Profile
While CAR T-cell therapy demonstrated significant efficacy, the analysis also highlighted the incidence of adverse events. Any-grade cytokine release syndrome (CRS) occurred in 86% (95% CI, 81%-91%) of patients, with grade 3 or higher CRS observed in 8% (95% CI, 5%-11%) of patients. Immune effector cell–associated neurotoxicity syndrome (ICANS) of any grade was reported in 52% (95% CI, 43%-61%) of patients, and the rate of grade 3 or higher ICANS was 22% (95% CI, 14%-30%).
Subgroup Analysis
Subgroup analyses were conducted to evaluate the impact of prognostic factors on treatment outcomes. Patients with a Ki-67 index below 30% had an ORR of 87% and a CR rate of 65%, while those with a Ki-67 index of 30% or more had an ORR of 88% and a CR rate of 74%. The presence or absence of TP53 mutations also influenced outcomes, with patients lacking these mutations showing a higher ORR (95%) and CR rate (81%) compared to those with TP53 mutations (ORR 89%, CR rate 70%).
Impact of Prior Therapies
The study also assessed the impact of prior therapies on CAR T-cell treatment outcomes. Patients who had not received prior BTK inhibitor treatment exhibited an ORR of 93% and a CR rate of 83%, whereas those with a history of such treatment exhibited an ORR of 83% and a CR rate of 70%. Patients who underwent prior hematopoietic stem cell transplantation (HSCT) had a higher CR rate (83%) compared to those without prior HSCT (70%).
Brexu-cel vs. Other CAR T-Cell Therapies
An analysis comparing brexucabtagene autoleucel (brexu-cel; Tecartus) with other CAR T-cell therapies revealed similar ORRs and CR rates. However, brexu-cel was associated with a higher incidence of CRS and ICANS, particularly grade 3 ICANS, but showed better short-term efficacy with higher 6-month PFS and OS rates.
Real-World vs. Clinical Trial Data
Investigators compared data from retrospective studies (456 patients) with prospective studies (528 patients) to identify discrepancies between real-world and clinical trial results. Retrospective studies showed a higher ORR (91%) and CR rate (77%) compared to prospective studies (ORR 86%, CR rate 70%). However, prospective studies demonstrated better 12-month PFS and OS rates.
Clinical Implications
"CAR-T therapy is highly effective as a salvage treatment for relapsed/refractory MCL, even in patients with high-risk features," Dr. Wan and colleagues wrote. They also noted that the variability in patient responses underscores the importance of personalized treatment approaches. The findings support the use of CAR T-cell therapy in MCL, particularly after failure of other treatments, including BTK inhibitors. The FDA has approved brexucabtagene autoleucel and lisocabtagene maraleucel for relapsed/refractory MCL, based on data from the ZUMA-2 and TRANSCEND NHL 001 trials, respectively.
Future Directions
Despite the promising results, the study authors emphasized the need for longer follow-up to determine the long-term efficacy of CAR T-cell therapy in MCL. "Future research should focus on long-term efficacy assessments to optimize treatment strategies and improve overall patient outcomes," the authors concluded.
