CAR T-Cell Therapy Delivers Durable QOL Gains at 2 Years

Patients treated with chimeric antigen receptor (CAR) T-cell therapy for aggressive blood cancers report broad, lasting improvements across physical functioning, sleep, and social engagement that extend well past the acute recovery period, according to a new longitudinal study tracking survivors for 2 years after infusion.^1,2

The data also show that early disparities in symptom burden by age and sex tend to narrow over time, and that a temporary rise in fatigue shortly after treatment may offer clinicians an early clue to which patients are most likely to respond.

The study, published in Blood Neoplasia, followed 83 adults treated with commercial or investigational CAR-T products at the University of Chicago between 2021 and 2025, collecting patient-reported outcome (PRO) data at 13 points spanning the day of infusion through 2 years afterward.¹ Most participants had aggressive lymphoma or multiple myeloma, and nearly all had already gone through at least 2 prior lines of therapy before receiving CAR-T.

“There have not been many studies asking patients what their quality of life is like only two weeks after their CAR T-cell therapy,” senior author Ajay Major, MD, MBA, assistant professor of medicine in the Division of Hematology at the University of Colorado Anschutz Medical Campus and co-lead of the imPROve Patient-Reported Outcomes Working Group, stated in a news release.²

Investigators used the Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health-10 and PROMIS-29 Profile instruments to track health-related quality of life (HRQOL) across 9 domains, including fatigue, physical function, sleep disturbance, anxiety, depression, pain interference, and social role function.¹ Scores were analyzed with linear mixed-effect modeling to chart trajectories over time and to compare patients by age, sex, and treatment response.

“When you can accurately predict what quality of life looks like over time, that's super important for a patient, especially now that people are surviving longer after their CAR-T therapies,” first author Vincenzo Pizzuti, MD, MS, chief resident in the University of Colorado's Internal Medicine Residency Training Program, stated in the news release.²

Across the full cohort, physical function, sleep disturbance, and social role functioning all trended toward improvement over the 2 years following infusion, a pattern that held regardless of whether patients were older or younger than 65 years.¹ Fatigue, which worsened acutely in the early weeks after infusion alongside declines in social and physical functioning, also improved over the long term. Anxiety, depression, global mental health, and pain interference remained comparatively stable throughout follow-up.

Age and Sex Gaps Narrow Over Time

Differences by age emerged only after the immediate post-infusion window. At day 15, older and younger patients reported similar fatigue, physical function, global physical health, and social role function. By day 30, however, patients 65 years and older showed significantly greater worsening of physical function than those younger than 65 (P = .0496, adjusted for multiple comparisons). That gap closed by 2 years, when both age groups showed comparable gains across HRQOL domains.

A parallel pattern appeared by sex. At baseline, men reported less fatigue and better global physical health, physical function, and social role function than women, with no significant sex-based differences in the trajectories at day 15 or day 30. By 2 years, though, women had significantly greater improvement than men in both fatigue (P = .0155) and global physical health (P = .0414), a shift the authors say appears to erase much of the initial disparity.

Fatigue Trajectory as a Possible Marker of Response

Among the study's several findings, one centered on the relationship between early fatigue and eventual disease response. Patients who went on to respond to CAR-T by day 90 reported significantly worse fatigue at day 15 than those who did not respond (P = .043), despite no difference in fatigue at baseline or in other HRQoL domains at that time point. That gap had disappeared by day 30 (P = .954). Over the full 2-year period, responders reported significantly better social role function than nonresponders (P = .041) and a nonsignificant trend toward greater fatigue improvement (P = .0577).

"These findings very much match what we see in actual clinical practice," Major said. "When we see worsening fatigue in the 2 weeks after CAR T, as we demonstrated in the study, what that probably reflects is that the inflammatory proteins, cytokines, that are being produced by the CAR T cells to help them kill cancer cells cause fatigue."²

Cytokine release during CAR-T cell expansion has previously been linked to acute toxicity and to systemic metabolic strain, a mechanism the authors propose could explain why more robust early immune activity, and more pronounced early fatigue, tracks with better later outcomes.³

The authors propose that patient-reported fatigue in the acute post-infusion period could serve as a low-cost "PRO marker" of subsequent response, similar in concept to biomarkers already used to gauge treatment activity in other hematologic malignancies, and one they say warrants prospective validation in larger cohorts.¹ Prior work in diffuse large B-cell lymphoma has also linked longitudinal PRO changes to progression-free and overall survival, lending support to the broader premise that symptom trajectories carry prognostic signal beyond scans and labs.⁴

"It could give you a tool to better understand which patients have the greatest need for an early disease response assessment," Pizzuti said.²

Response Rates and Safety

By day 90, the overall response rate was 78% among patients with lymphoma and 92% among those with multiple myeloma. Across the entire cohort, the best response achieved at any point was complete response or stringent complete response in 65% of patients, partial response or very good partial response in 17%, stable disease in 3%, and progressive disease in 14%. Median follow-up was 15.1 months, median time to progression was 439 days, and median time to death or censoring was 578 days.

Toxicity was consistent with prior CAR-T experience. Cytokine release syndrome (CRS) occurred in 81% of patients, none of grade 3 or higher, and immune effector cell-associated neurotoxicity syndrome developed in 20%, with grade 4 or 5 events in 6%. CRS occurrence was not significantly associated with day 90 response status (P = .52).

Limitations and Takeaways

The authors cautioned that the cohort was drawn from a single academic CAR-T biobank, limiting generalizability, and that the modest sample size precluded subgroup comparisons by specific CAR-T product or disease subtype. Because 95% of patients had received 2 or more prior lines of therapy, the results may not fully reflect outcomes in patients receiving CAR-T earlier in their disease course. Survey completion also declined at later time points, and differential attrition, driven by higher rates of death or relapse among nonresponders, may have understated fatigue differences in extended follow-up.

Even with those caveats, the researchers said the data offer oncologists a more concrete basis for counseling patients before and after infusion. "When I see patients and I'm talking about CAR T-cell therapy," Major said, "this data allows me to tell them more about their expected quality-of-life trajectory in the short term and in the long term."²

REFERENCES

1. Pizzuti VJ, Dunn A, Colborn K, et al. Longitudinal patient-reported outcomes and quality-of-life trajectories over 2 years in CAR-T therapy recipients. Blood Neoplasia. 2026;3(4):100278. doi:10.1016/j.bneo.2026.100278

2. Harden M. CAR T-cell therapy is a blood cancer breakthrough. But what about quality of life? CU Anschutz Cancer Center News. Published September 2, 2026. Accessed September 3, 2026. https://tinyurl.com/cc9jvmmu

3. Fischer JW, Bhattarai N. CAR-T cell therapy: mechanism, management, and mitigation of inflammatory toxicities. Front Immunol. 2021;12:693016. doi:10.3389/fimmu.2021.693016

4. Huang H, Datye A, Fan M, et al. Patient-reported outcomes provide prognostic information for survival in patients with diffuse large B-cell lymphoma: analysis of 1239 patients from the GOYA study. Cancer Med. 2022;11(17):3312-3322.