CAR T-Cell Therapy Yields Swift QoL Boost in Childhood ALL

Chimeric antigen receptor (CAR) T-cell therapy led to quick gains in quality of life (QoL) for children and young adults with relapsed or refractory acute leukemia, a patient-reported outcomes analysis from the ELIANA trial indicated.

Among this group of acute lymphoblastic leukemia (ALL) patients treated with tisagenlecleucel (Kymriah), higher scores on two validated QoL questionnaires were seen as early as day 28 across most domains, which reached clinically meaningful numbers by month 3, Theodore Laetsch, MD, of University of Texas Southwestern Medical Center in Dallas, and colleagues reported.

"Rapid improvements in broad aspects of patient-reported quality of life occurred after one-time treatment with tisagenlecleucel," the authors wrote in the Lancet Oncology. "Some delay in quality-of-life improvement was noted in patients who had severe cytokine release syndrome or neurotoxicity, but meaningful improvements in quality of life were still evident in these groups of patients by months 3-6."

For their study, Laetsch's group examined patient-reported QoL in 58 ALL patients ages 8 to 23 with relapsed or refractory disease who underwent treatment with tisagenlecleucel in the ELIANA trial, the international multicenter phase II study that led to the FDA's 2017 approval of the CAR T-cell product. Recently reported long-term data from the trial has demonstrated durable responses in these patients.

QoL was evaluated at baseline, and at multiple time points through 1 year, using the Pediatric Quality of Life Inventory (PedsQL) and European Quality of Life-5 Dimensions visual analogue scale (EQ-5D VAS) questionnaires. PedsQL tracks individual scores for emotional, school, social, and physical functioning, and also has a psychosocial health summary score. EQ-5D VAS measures overall health status. In both 100-point scales, higher scores indicate better QoL.

At baseline, over 80% of tisagenlecleucel-treated patients completed the two questionnaires, and mean patient scores were suppressed for all domains compared with healthy children (58.0 vs 83.0 for the PedsQL total score; 66.8 vs 86.2 on EQ-5D).

"Between months 3 and 12, improvements from baseline in patient-reported quality of life were observed for all measures, which increased over time," Laetsch and co-authors wrote. "Generally, these improvements from baseline were smallest for social functioning and greatest for physical functioning."

By month 3, the total score on the PedsQL improved by 13.3 points, with the largest gains seen with emotional functioning (7.3 points) and the lowest with physical functioning (0.2 points). By 1 year, only half of the group reached normal ranges for physical functioning.

Mean improvements from baseline on the EQ-5D VAS were 16.8 at the 3-month time point, 17.4 at 6 months, 18.8 at 9 months, and 24.7 at 1 year.

A post-hoc analysis found smaller day-28 improvements for patients who experienced severe cytokine release syndrome, versus those who didn't, on both questionnaires (0.3 vs 7.1 for the PedsQL total score; 3.3 vs 12.2 on EQ-5D VAS). But improvements for both groups became similar by months 3 and 6 and these gains were sustained by month 12, the authors noted. A similar pattern played out for patients who experienced severe neurotoxicity.

"This finding is important because in the original trial, cytokine release syndrome and neurological events were major safety concerns, with cytokine release syndrome occurring in 77% of patients and neurotoxicity occurring in 40%," wrote Fabio Efficace, PhD, and Marco Vignetti, MD, both of the Italian Group for Adult Hematologic Diseases in Rome, in an accompanying editorial.

But they noted that the questionnaires used for this analysis do not contain measures of cancer symptoms, instead focusing on overall health and psychosocial domains.

"Given the specific toxicity profile of CAR T-cell therapies, evaluation of (patient-reported) symptomatic adverse events is recommended," Efficace and Vignetti wrote. "It will also be important to investigate long-term quality-of-life outcomes (i.e., beyond the 12-month period of observation) in this younger acute lymphoblastic leukemia population, by including an evaluation of symptoms and cognitive aspects, and possibly to compare findings with long-term quality-of-life data of patients treated with traditional therapies for acute lymphoblastic leukemia."