Tisagenlecleucel appears less toxic among CAR-Ts for advanced follicular lymphoma
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Tisagenlecleucel may be less toxic than axicabtagene ciloleucel for patients with relapsed or refractory follicular lymphoma, study results suggested.
Results of an indirect comparison study presented at Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR showed patients who received axicabtagene ciloleucel (Yescarta; Kite Pharma/Gilead Sciences) for advanced follicular lymphoma experienced significantly higher incidence of cytokine release syndrome and neurotoxicity than those who received tisagenlecleucel (Kymriah, Novartis).
“The main take-home message is that both of these agents appear active and effective for an in-need population of patients,” Michael Dickinson, MBBS, DMedSci, lymphoma lead at Peter MacCallum Cancer Centre and Royal Melbourne Hospital, told Healio. “Tisagenlecleucel might be a better option if toxicity is a primary concern.”
Background and methodology
Tisagenlecleucel and axicabtagene ciloleucel are autologous, CD19-directed chimeric antigen receptor T-cell therapies.
Axicabtagene ciloleucel — also known as axi-cel — is approved by the FDA for adults with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy. Tisagenlecleucel is undergoing priority review by the FDA for the same indication.
Randomized, head-to-head trials of different CAR-T products are unlikely, Dickinson said.
Dickinson and colleagues conducted a matched indirect comparison study based on propensity score weighting to compare populations from different trials while adjusting for the different characteristics of each patient population.
Researchers used individual patient-level data from the ELARA trial of tisagenlecleucel to match with baseline characteristics based on aggregated summary data from the ZUMA-5 trial of axi-cel.
The ZUMA-5 trial did not allow for use of bridging chemotherapy; therefore, the study’s primary analysis compared a subgroup of patients who did not receive bridging therapy in the ELARA study (n = 53) with patients in the ZUMA-5 trial (n = 124).
Efficacy outcome comparisons used data from patients in both studies who had 12 months or more of follow-up. Safety analyses included all patients who received a CAR-T infusion during their respective study.
Researchers performed a separate sensitivity analysis to compare patients with or without bridging chemotherapy in either study.
Key findings
Primary analysis results revealed similar overall (92.5% vs. 94%) and complete (77% vs. 79%) response rates with tisagenlecleucel and axi-cel.
Researchers observed similar PFS between the two groups, both before (HR = 1.02; 95% CI, 0.52-1.99) and after (HR = 0.9; 95% CI, 0.39-2.06) weighting. Likewise, results showed similar OS from the time of CAR-T infusion between the two groups, both before (HR = 0.45; 95% CI, 0.13-1.59) and after (HR = 0.33; 95% CI, 0.07-1.57) weighting.
After weighting, results showed significantly lower rates of all-grade CRS (45.5% vs. 78%) and neurotoxicity (8.75% vs. 56%) among tisagenlecleucel-treated patients than those who received axi-cel (P < .05 for both).
Researchers observed a similar trend after weighting for high-grade toxicities, with patients who received tisagenlecleucel experiencing significantly lower rates of high-grade CRS (0 vs. 6%) and neurotoxicity (0.29% vs. 15%) than those who received axi-cel (P < .05 for both).
Investigators reported similar results in the sensitivity analysis that accounted for patients with and without bridging therapy in the ELARA trial.
Results showed similar efficacy outcomes between studies before and after weighting, whereas tisagenlecleucel showed significantly lower rates of overall and high-grade CRS or neurotoxicity.
Clinical implications
Dickinson cautioned that the results of this matched indirect comparison study are not powered to reach the same conclusions that a randomized trial would allow. Other limitations include lack of individual data from ZUMA-5 trial and the relatively small sample size.
Efficacy outcomes appeared similar — both before and after adjusting for patient characteristics — but the differences observed in terms of toxicity suggest that use of tisagenlecleucel was associated with better safety outcomes, he added.
“Unfortunately, the follow up of the two studies is too short to draw firm conclusions on differences in survival,” he told Healio. “I consider this data as contributing to our understanding of what might account for numerical differences in the results of the CAR-T trials.”
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Dickinson M, et al. Abstract 77. Presented at: Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR; April 23-26, 2022; Salt Lake City.
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