Immuno-Oncology Resource Center

Immuno-Oncology Resource Center

December 06, 2019
5 min read

Children, young adults experience ‘rapid improvement’ in quality of life after CAR-T for ALL

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Photo of Theodore Laestch
Theodore W. Laetsch

Children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia reported sustained, clinically meaningful improvement in quality-of-life scores after receiving chimeric antigen receptor T-cell therapy, according to an analysis of the single-arm, phase 2 ELIANA trial published in The Lancet Oncology.

Researchers observed the greatest improvement in physical function, followed by emotional function and school function.

“Improvements started within a month of treatment and were sustained for up to a year, the longest timepoint included in our study,” Theodore W. Laetsch, MD, associate professor of pediatrics at The University of Texas Southwestern Medical Center, told Healio. “[Although] the timing of improvement was somewhat delayed, improvements in quality of life were seen within 3 months, even for patients who experienced severe cytokine release syndrome or neurotoxicity.”

Laetsch said the study, which he co-authored, is the first to describe patient-reported outcomes after CAR T-cell therapy.

“Our goal was to gain a better understanding of the impact of tisagenlecleucel [Kymriah, Novartis] on the quality of life of children with relapsed or refractory leukemia,” Laetsch said. “Many of the therapies used to treat cancer in children, including stem cell transplant, can have lasting impacts on quality of life, and understanding these impacts is important as patients and providers weigh the risks and benefits of various treatment options.”

Laetsch noted that CAR T-cell therapy already has demonstrated unprecedented efficacy among this patient population. In the global, open-label ELIANA trial, 61 of 75 children and young adults (81%) with relapsed or refractory B-cell ALL experienced complete remission after an infusion of tisagenlecleucel, an anti-CD19 CAR T-cell therapy.

Laetsch and colleagues analyzed patient-reported quality of life (QOL), a prespecified secondary endpoint of the trial.

Quality of life in ELIANA

Patients in the ELIANA trial received a single IV dose of 0.2 to 5 x 106 transduced viable T cells/kg for patients weighing no more than 50 kg or 0.1 to 5 x 108 transduced viable T cells/kg for those weighing more than 50 kg. Researchers in the current study evaluated quality of life among patients at baseline and 28 days and 3, 6, 9 and 12 months after treatment as measured by two previously validated questionnaires, the Pediatric Quality of Life Inventory (PedsQL) and the European Quality of Life-5 Dimensions (EQ-5D) VAS.

The quality-of-life analysis included 58 patients aged 8 to 23 years. Fifty of these patients (86%) completed the PedsQL questionnaire and 48 (83%) completed the EQ-5D questionnaire at baseline. Among the 48 patients in the analysis who responded to treatment, 83% provided EQ-5D data and 90% provided PedsQL data.


Median follow-up among treatment responders was 9.9 months (interquartile range, 5.3-13.5).

Mean age of patients who provided baseline and at least one post-infusion QOL assessment (n = 48) was 14.3 years (standard deviation, 4.5); 60% of these patients were male, 79% were white and 62% had undergone previous hemopoietic stem cell transplantation.

“The number of patients who remained on study and thus eligible to submit patient-reported quality-of-life-data decreased at each successive study visit,” Laetsch and colleagues wrote, adding that the number of patients dropped to 47 patients at 3 months, 25 patients at 9 months and 14 patients at 12 months.

Baseline scores for all patient-reported QOL categories were below the normative means, with relative reductions ranging from 17% to 43% for emotional, social, school and physical function and psychosocial health summary.

Researchers observed increases in patient-reported scores for all QOL measurements at 3 months after tisagenlecleucel infusion. Mean change from baseline to 3 months was 13.3 (95% CI, 8.9-17.6) for the PedsQL total score and 16.8 (95% CI, 9.4-24.3) for the EQ-5D VAS. Minimal clinically important difference between baseline and 3 months after infusion was achieved by 30 of 37 patients (81%) for the total PedsQL total score and 24 of 36 patients (67%) for the EQ-5D VAS.

Compared with baseline, a greater proportion of patients reported no problems on the EQ-5D questionnaire at day 28 and months 3, 6, 9 and 12 in all areas but self-care, which was lower than the baseline value at day 28.

Emotional functioning showed the greatest mean improvement from baseline among PedsQL scores at day 28 after infusion (7.3; 95% CI, 1.6-13.1), whereas the least mean improvement occurred in school functioning (0.2; 95% CI, –8.3 to 8.8). All patient-reported QOL measures showed improvements from baseline between months 3 and 12.

“Having treated children with tisagenlecleucel, I knew that patients’ quality of life improved after therapy,” Laetsch told Healio. “However, I was surprised by the speed of improvement that we identified in this study.”

Post-hoc subgroup analyses suggested that patients with severe cytokine release syndrome or neurotoxicity had lower mean improvement in QOL at day 28 than patients who did not; however, these patients showed improvements by months 3 and 6 that continued through month 12.

The single-arm design of the study, which lacked a comparison group of patients who underwent standard therapies, served as its primary limitation, according to researchers.


Clinical implications

The study authors should be commended for their work providing the scientific community with “unprecedented” patient-reported outcomes information on the burden of CAR T-cell therapy, according to Fabio Efficace, PhD, and Marco Vignetti, MD, of the Italian Group for Adult Hematologic Diseases.

“Although efficacy and safety data of tisagenlecleucel were previously documented in the pivotal study ... only by reading Laetsch and colleagues’ article can we appreciate how this therapy has affected patients’ lives, from their own perspective,” Efficace and Vignetti wrote in an accompanying editorial.

No similar comprehensive QOL analysis of patients who have received CAR T-cell therapy has been undertaken to date, they added. Nevertheless, they noted that the study is limited by the QOL measures chosen by the investigators.

“No information regarding key cancer symptoms can be obtained from these measures,” they wrote. “The questionnaires used in their study were mainly focused on capturing more general health and psychosocial aspects, thereby limiting a thorough understanding of patient-reported symptom burden. Given the specific toxicity profile of CAR T-cell therapies, evaluation of (patient-reported) symptomatic adverse events is recommended.”

Laetsch said that the impact of the study goes beyond treatment efficacy. Current research should now be directed toward moving CAR T-cell therapy into earlier lines of therapy, given its overall effect on improving patients’ QOL.

“Our findings demonstrating rapid improvement in quality of life cement this as a preferred option for these patients and suggest that clinical trials testing CAR T-cell therapy earlier in the disease course are warranted,” he told Healio.

Laetsch confirmed that such trials are ongoing, including one studying the use of tisagenlecleucel as front-line therapy for children and young adults with very high-risk B-cell ALL.

“In our study, although quality of life improved, only about half of patients reached the normal range for physical functioning at 1 year after treatment,” he said. “Although it is not possible to separate the impact of CAR T-cell therapy and prior chemotherapy in our data, some of this persistent impairment in physical functioning may represent chronic toxicity from prior lines of therapy. Thus, I am hopeful that quality of life for patients treated with tisagenlecleucel will be further improved when given earlier.” – by Drew Amorosi

For more information:

Theodore W. Laetsch, MD, can be reached at Children's Medical Center of Dallas, 1935 Medical District Drive, Dallas, TX 75235; email:

Disclosures: The study was funded by Novartis. Laetsch reports grants from Novartis related to the study and from Pfizer; personal fees and nonfinancial support related to the study from Novartis; and personal fees from Bayer, Eli Lilly and Loxo Oncology. Please see the study for all other authors’ relevant financial disclosures. Efficace reports grants from Amgen and Bristol-Myers Squibb, and personal fees from Amgen, Bristol-Myers Squibb, Incyte, Orsenix and Takeda. Vignetti reports personal fees from Amgen, Novartis and Pfizer.