Introduction: Chimeric antigen receptor (CAR) T-cell therapy has transformed the management of patients with hematologic malignancies; however, it is also associated with unique side effects that may impact rehabilitation needs post-treatment. Despite improvements in survivorship, the knowledge of rehabilitation needs in patients after CAR T-cell therapy remains limited. This retrospective study aims to identify factors associated with rehabilitation needs following CAR T-cell treatment for lymphoma.

Methods: A single-center retrospective analysis was conducted on patients with lymphoma who received commercial CD19-directed CAR T-cell therapy. Patient characteristics (age, sex, line of therapy, ECOG performance status, CAR-T product, HCT-CI score), disease-related characteristics (lymphoma subtype, LDH, albumin, CRP, and ferritin, as well as recent weight loss), and treatment-related complications (presence and severity of CRS and ICANS, length of initial hospitalization, and duration of unplanned hospitalizations) were collected. Logistic regression was used to evaluate the association between patient characteristics and treatment-related complications, and recommendations by physical (PT) or occupational therapy (OT) for home health (HH), skilled nursing facility (SNF) or acute inpatient rehabilitation (AIR) within 30 days of CAR-T.

Results: 99 lymphoma patients were included, with a median age at collection of 65 years (age range 24-81). 58% were female. Lymphoma subtypes included diffuse large B-cell lymphoma (n=78), follicular lymphoma (n=10), and mantle cell lymphoma (n=11). CAR-T products included axi-cel (n=52), tisa-cel (n=7), liso-cel (n=29), and brexu-cel (n=11). 10% had an ECOG ≥ 2. CRS occurred in 68% (0 ≥ grade 3), and ICANS occurred in 35% (6% ≥ grade 3). 48% were hospitalized for CAR T-cell infusion, 33% were treated outpatient but hospitalized post treatment, and 18% were outpatient for the first month post CAR-T. 64% had a complete response, 17% partial response, 16% progressive disease, and 2% were not evaluable post CAR-T cell therapy.

Out of 49 patients assessed by PT and OT during any inpatient stay within 30 days of CAR-T cell infusion, 39 patients (80%) were recommended skilled rehabilitation services including HH (n=22), SNF (n=9), or AIR (n=8). Among these, 21 patients were discharged with HH, 1 was discharged to SNF, and 5 were discharged to AIR (95%, 11%, and 63% of referred for these services, respectively).

Pretreatment/baseline characteristics significantly associated with recommendations for skilled rehabilitation services included female sex (p=.03), receipt of brexu-cel (p=.04), diagnosis of mantle cell lymphoma (p=.03), higher ECOG score (ECOG ≥ 2) (p=.001), lower albumin (p=.002), and elevated CRP (p=.03) at time of CAR-T infusion. Post-treatment complications, including the presence and grade of CRS (p=.002 and p=.004, respectively) and ICANS (p<.0001 for both), initial hospital length of stay for those treated inpatient (p=.008), and length of unplanned hospitalization for outpatients requiring admission (p=.01), were associated with a higher chance of being recommended rehabilitation. Recommendation for rehabilitation was not significantly associated with response to CAR-T therapy. In models controlling for outpatient versus inpatient CAR-T infusion, given that only hospitalized patients are assessed for services, several factors were significantly associated with recommendations for skilled services at discharge, including ECOG status (p=.004), increased prior lines of therapy (p=.04), older age (p=.03), decreased albumin (p=.006), female sex (p=.04), CRS and CRS grade (p=.009 and .02, respectively), ICANS and ICANS grade (p<.0001 and p=.0002, respectively). Elevated CRP showed borderline significance (p=.07). Type of CAR-T product (p=.25) and lymphoma subtype (p=.15) were not significantly associated in the adjusted model.

Discussion: A high proportion of lymphoma patients treated with CAR-T cells have reduced functional status requiring skilled rehabilitation services within the first month of treatment. Baseline pre-treatment characteristics including reduced performance status, decreased albumin, and elevated CRP as well as post-treatment complications including CRS and ICANS are associated with recommendations for rehabilitation. Prospective studies evaluating the role of prehabilitation and other focused interventions for patients receiving CAR-T cell therapy are needed.

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2025
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