CAR-T Cell Therapy Bests Standard of Care in Health-Related Quality of Life for Patients With Lymphoma

Most patients with large B-cell lymphoma reported positive outcomes and maintenance or improvements in health-related quality of life after receiving second-line Breyzani (liso-cel; lisocabtagene maraleucel), according to findings from the phase 3 TRANSFORM trial.

An analysis of the study presented at the 2021 ASH Annual Meeting, showed that treatment with Breyzani — a CAR-T cell therapy — induced more favorable changes from baseline to day 126 than the standard of care in most of the 30 items found in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Higher scores on the questionnaire represent higher functioning and quality of life.

Specifically, the difference between treatments in terms of cognitive functioning was 2.21 for those treated with Breyzani vs -2.09 with standard of care; the average difference between the treatments for physical functioning was -2.75 and -2.17, respectively. The difference in score between each group was deemed to be statistically significant. Moreover cognitive functioning and physical functioning in the standard of care group tended to deteriorate over time, as the CAR-T cell therapy group was noted to improve.

The individual-level analyses showed that a higher proportion of patients in the Breyzani group improved when it came to fatigue and global health/quality of life (GH/QOL) compared with standard of care. Similarly, a smaller percentage of patients on Breyzani deteriorated than the standard of care group.

Notably, a higher proportion of patients in the standard of care group experienced worsened fatigue (71%) vs. the Breyzani group (18%), and a lower proportion experienced improvement in fatigue, at 29% and 47%, respectively.

A higher proportion of patients in the standard of care group experienced worsened GH/QOL vs. the CAR-T cell therapy group, at 57% and 18%, respectively; moreover, a lower proportion of patients had improved GH/QOL, at 14% and 53%, in the standard of care and Breyzani groups, respectively.

Regarding the other main goals, the proportions of patients with improvement or deterioration favored Breyzani or proved to be similar between the treatment groups.

“Compared with standard of care, liso-cel (Breyzani) showed favorable improvement in most primary (patient reported outcome) domains, particularly EORTC QLQ-C30 cognitive functioning and fatigue and more patients showed (patient reported outcome) improvements and fewer showed deterioration by month six with liso-cel,” lead study author Dr. Jeremy S. Abramson, of the Lymphoma Program at Massachusetts General Hospital Cancer Center in Boston, and colleagues, wrote in the abstract on the data.

Not only did it improve quality of life, but Breyzani’s cancer-fighting abilities were also examined in the TRANSFORM study. The CAR-T cell therapy demonstrated a meaningful improvement in the event-free survival (time after primary treatment ends that a patient remains free of certain complications the treatment was intended to prevent or delay) in this patient population, with no new safety signals observed.

TRANSFORM enrolled patients who were aged 75 years or younger who had relapsed or refractory large B-cell lymphoma and had completed their first-line therapy within 12 months of enrollment. To be eligible for enrollment, patients needed to have been candidates for autologous stem cell transplantation (ASCT).

Study participants were randomized to receive either standard of care, which consisted of three cycles of salvage chemotherapy and carmustine, etoposide, cytarabine and melphalan, plus ASCT for responding patients, or Breyzani following lymphodepletion (a short course of chemotherapy given before CAR-T cell therapy to kill T cells). Notably, patients assigned to the standard of care group were permitted to crossover to receive lymphodepletion if they experienced disease progression.

The EORTC QLQ-C30 and Functional Assessment of Cancer Therapy - Lymphoma Subscale (FACT-LymS) (another quality of life assessment) were administered to patients at the time of randomization, as well as on day 29 (infusion of Breyzani or two cycles of salvage chemotherapy), day 64 (one month post Breyzani or completion of chemotherapy), and day 126 (three months after Breyzani or two months after ASCT), at six months, and other prespecified time points up to 36 months following treatment. No patient-reported outcomes were collected for those who crossed over from standard of care to Breyzani.

The analysis was based on the patient-reported outcome-evaluable population, or those who completed an assessment at baseline, as well as at least one post-baseline assessment, and predefined thresholds determined clinically meaningful changes.

Primary areas of interest included GH/QOL, physical functioning, cognitive functioning, fatigue, pain, and FACT-LymS, and an analysis performed to assess the between-treatment difference in changes from baseline for each group. Furthermore, proportions of patients with meaningful change from baseline were assessed for each primary domain up to six months.

Additional data showed that the overall average change in fatigue was -1.95 in the Breyzani group vs 3.75 in the standard of care group, and the overall average change in pain was -11.14 vs -15.56, respectively.

Additionally, the average score change in GH/QOL was 3.08 in the Breyzani group vs 0.04 in the standard of care group. The overall average change in the FACT-LymS was 1.48 in the Breyzani group vs. 1.63 in the standard of care group.

A version of this article was originally published on OncLive as “Liso-cel Improves HRQoL Over Standard of Care in Relapsed/Refractory LBCL.”

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