Associate Professor Michael Dickinson

Older adults with relapsed or refractory large B-cell lymphoma appear to benefit more from second-line CAR T-cell therapy than the overall cohort in the ZUMA-7 trial.

The findings should help inform treatment decisions if and when axicabtagene ciloleucel (axi-cel) becomes available in the second line, Blood 2022 was told.

Associate Professor Michael Dickinson, from the Peter MacCallum Cancer Centre in Melbourne, presented a pre-planned subgroup analysis on 109 patients aged ≥65 years.

Associate Professor Dickinson reminded the meeting that the overall ZUMA-7 trial of axi-cel versus standard of care favoured the CAR T therapy. It found axi-cel significantly improved event-free survival (8.3 v 2.0 months) with a hazard ratio for event or death of 0.398.

However the outcome in older patients warranted investigation given they typically suffered more from toxicities from conventional chemotherapy, which in turn made it difficult to deliver salvage regimens.

“In addition health-related quality of life (HR-QOL) deteriorates after exposure to conventional chemotherapy particularly in older patients,” he said.

Associate Professor Dickinson said the axi-cel and standard of care arms were well matched with a slightly higher risk group in the axi-cel arm.

“In this older population, the HR was 0.276 – strongly statistically significant – in favour of the axi-cel arm after a median follow-up of two years.”

“This translates to a 21.5 month median event-free survival in the CAR T arm versus 2.5 months in the standard of care arm.”

As well, 47.8% of axi-cel recipients were event-free at 2 years compared to 15.1% in the standard of care group.

The overall response rates (88% v 52%) and complete response rates (75% v 33%) further confirmed a stronger benefit from axi-cel in this older subgroup than in the overall cohort.

Associate Professor Dickinson said an interim overall survival analysis showed prolonged survival in the axi-cel group with estimated a HR of 0.517, although longer follow-up was required.

“The Kaplan-Meier estimate of OS at 2 years was 64% in the axi-cel arm and 51% in the standard of care arm.”

“It’s worth noting that there was an effective crossover in a proportion of patients – 57% of patients in the standard of care group effectively crossed over by subsequently receiving a cellular immunotherapy off-study,” he added.

The meeting was told the safety data was unsurprising with all patients reporting adverse events including pyrexia, neutropenia and nausea.

CRS also occurred in almost all patients exposed to axi-cel and grade ≥3 CRS in 8% of those patients. Neurologic events occurred in 65% of patients in the axi-cel arm and Grade ≥3 in 27%.

“The median time to onset for neurotoxicity was 7 days and the median duration was 9 days.”

Progressive disease was the cause of death in 19 patients in the axi-cel group and 20 patients in the standard of care group.

Associate Professor Dickinson said HR-QOL measures including EORTC-QLQ-C30 and EQ-5D-5L also favoured of axi-cel versus standard of care.

“In the overall ZUMA-7 study, this was only statistically significant at two time points but in this older population, it’s statistically and clinically significant across all time points.”

“These data demonstrate that age is less of an important predictor of tolerability of treatment with CAR T cell therapy than we might have expected,” he concluded.

“For years and years we have known that age portends less tolerance to standard chemotherapy but we haven’t seen that with ZUMA-7. You might have guessed that …older patients wouldn’t have experienced the same benefit but in fact older patients appear to have more benefit from CAR T cell therapy than the overall study,” he told the limbic.