Second-line lisocabtagene maraleucel demonstrated a favorable improvement in most patient-reported outcome domains compared with standard of care in patients with relapsed or refractory large B-cell lymphoma, and health-related quality of life was found to either be improved or maintained following treatment with the CAR T-cell therapy.
Second-line lisocabtagene maraleucel (liso-cel; Breyzani) demonstrated a favorable improvement in most patient-reported outcome domains compared with standard of care (SOC) in patients with relapsed or refractory large B-cell lymphoma (LBCL), and health-related quality of life (HRQoL) was found to either be improved or maintained following treatment with the CAR T-cell therapy, according to data from the phase 3 TRANSFORM trial (NCT03575351).1
Results from a linear mixed model for repeated measures (MMRM) analysis, which will be presented during the 2021 ASH Annual Meeting, showed that liso-cel had more favorable overall least squares (LS) mean changes from baseline to day 126 than the SOC arm in most of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – 30 items (EORTC QLQ-C30) domains.
Specifically, the difference between treatments in terms of cognitive functioning was 2.21 (95% CI, -1.48 to 5.90) for those treated with liso-cel vs -2.09 (95% CI, -6.00 to 1.83) with SOC; the mean difference between the treatments fo physical functioning was -2.75 (95% CI, -6.76 to 1.25) and -2.17 (95% CI, -6.64 to 2.30), respectively. This was found to exceed the prespecified minimal importance difference threshold. Moreover, in those domains, the SOC arm deteriorated, as the CAR T-cell therapy arm was noted to improve.
Data from individual-level analyses showed that the proportion of patients with meaningful improvement in fatigue and global health/QOL (GH/QOL) was higher, and deterioration was lower in the liso-cel arm vs the SOC arm from baseline to 6 months. Notably, a higher proportion of patients in the SOC arm had experienced worsened fatigue (71%) vs the liso-cel arm (18%), and a lower proportion experienced improvement in fatigue, at 29% and 47%, respectively.
A higher proportion of patients in the SOC arm experienced worsened GH/QOL vs the CAR T-cell therapy arm, at 57% and 18%, respectively; moreover, a lower proportion of patients had improved GH/QOL, at 14% and 53%, respectively. Regarding the other primary domains, the proportions of patients with improvement or deterioration favored liso-cel or proved to be similar between the treatment arms.
“Compared with SOC, liso-cel showed favorable improvement in most primary PRO domains, particularly EORTC QLQ-C30 cognitive functioning and fatigue and more patients showed PRO improvements and fewer showed deterioration by month 6 with liso-cel,” lead study author Jeremy S. Abramson, MD, of the Lymphoma Program at Massachusetts General Hospital Cancer Center, and colleagues, wrote in the abstract on the data.
Patients with previously treated, relapsed or refractory, aggressive LBCL often have a compromised HRQoL. The CD19-directed, CAR T-cell therapy, liso-cel, was examined in the TRANSFORM study and demonstrated a statistically significant and clinically meaningful improvement in the primary end point of event-free survival in this patient population, with no new safety signals observed. At the 2021 ASH Annual Meeting, investigators will report data from the PRO analysis of the study.
TRANSFORM enrolled patients who were aged 75 years or younger who had relapsed or refractory LBCL and had completed their first-line therapy within 12 months of enrollment. Patients needed to have been candidates for autologous stem cell transplantation (ASCT).
Study participants were randomized to receive either SOC, which consisted of 3 cycles of salvage chemotherapy and carmustine, etoposide, cytarabine, and melphalan, plus ASCT for responding patients, or liso-cel following lymphodepletion. Notably, patients assigned to the SOC arm were permitted to crossover to receive liso-cel if they experienced disease progression.
The EORTC QLQ-C30 and FACT-LymS were administered to patients at the time of randomization, as well as on day 29 (infusion of liso-cel or 2 cycles of salvage chemotherapy), day 64 (1 month post liso-cel or completion of chemotherapy), and day 126 (3 months after liso-cel or 2 months after ASCT), at 6 months, and other prespecified time points up to 36 months following treatment. No PROs were collected for those who crossed over from SOC to liso-cel.
The analysis was based on the PRO-evaluable population, or those who completed an assessment at baseline, as well as at least 1 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 a linear MMRM analysis was performed to assess the between-treatment difference in overall LS mean change from baseline for each. Furthermore, proportions of patients with meaningful change from baseline were assessed for each primary domain up to 6 months.
Among the 184 patients randomized to either SOC or liso-cel, 90 (49%) and 85 (46%) were included in the PROs-evaluable population. The assessment completion rate was more than 45% in both study arms, which was lower than expected due to challenges from the COVID-19 pandemic.
Additional data showed that the overall LS mean change in fatigue was -1.95 (95% CI, -7.40 to 3.51) in the liso-cel arm vs 3.75 (95% CI, -2.17 to 9.68) in the SOC arm, and the overall LS mean change in pain was -11.14 (95% CI, -16.37 to -5.92) vs -15.56 (95% CI, -21.25 to -9.88), respectively.
Additionally, the overall LS mean change in GH/QOL was 3.08 (95% CI, -1.83 to 7.99) in the liso-cel arm vs 0.04 (95% CI, -5.24 to 5.31) in the SOC arm. The overall LS mean change in the Functional Assessment of Cancer Therapy - Lymphoma Subscale (FACT-LymS) was 1.48 (95% CI, -0.30 to 3.26) in the liso-cel arm vs 1.63 (95% CI, -0.41 to 3.68) in the SOC arm.