Physical Therapy Assessment of Baseline Function and Endurance Predicts Short Term Outcomes in Commercial CAR T Patients with Lymphoma

Introduction:

CAR T-cell therapy has revolutionized the treatment of relapsed/refractory B cell lymphomas, providing hope to patients who previously faced dismal outcomes. Despite unprecedented efficacy including high response rates and a significant proportion of durable responses, significant toxicities are still prevalent. Toxicities related to immune therapy including cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) along with infections and hematologic toxicity, complicate the post CAR T-cell infusion course. Innate patient-related factors including presence of comorbidities, advanced physiologic age, and poor fitness, likely contribute to poor short-term outcomes, however no validated risk scores incorporating these factors have been validated in patients receiving CAR T-cell therapy for lymphoma. In the present study we identified the ability of a patient to walk 500 feet (ft) or more during the 6 Minute Walk Test (6MWT) at baseline as a predictive marker for poor short-term outcomes after CAR T-cell infusion.

Methods:

We retrospectively analyzed charts of 78 patients who received commercially available CAR T-cell products for the treatment of lymphoma between May, 2019 and March, 2021 who had baseline assessment by physical therapy at the time of admission for CAR T-cell therapy. CRS and ICANS were scored by ASTCT guidelines. Demographics were analyzed with descriptive statistics. Univariate analysis was performed by Chi Squared.

Results:

The analysis included 78 patients with a median age of 63 (range, 21-82), 37% (n=29) were female. Patients were treated for DLBCL (64%, n=50), transformed follicular lymphoma (tFL; 29%, n=23), primary mediastinal B cell lymphoma (PMBCL; 4%, n=3), and mantle cell lymphoma (MCL; 3%, n=2). Patients received axicabtagene ciloleucel (94%, n=73), tisagenlecleucel (4%, n=3), or brexucabtagene autoleucel (3%, n=2). Patients had a median of 3 prior lines of therapy (range 2-7) and 53% (n=42) received bridging chemotherapy.

Among the 70 patients who completed the 6MWT, the mean distance was 909 ft (range, 20-2045), 8 patients were unable to compete the assessment due to debility and were included in the analysis as a 0 distance. Patients who were unable to complete 500 feet (n=17) were deemed to have poor endurance (PE). The PE group of patients were 3.6 times more likely to have a prolonged length of stay (p=0.02), while they were 1.5 times less likely to be alive at 100 days post CAR T infusion (p = 0.002). Patients also tended to have higher rates of ICANS (76% vs 41%), lower overall response rates (ORR) (78% vs 98%), and higher 30 day mortality (18% vs 2%), although these did not reach statistical significance, p=0.08, 0.06, and 0.07, respectively. CRS did not appear to be related to PE status, neither did age, or prior lines of therapy.

Conclusions:

Within the limitations of a retrospective study, we demonstrate that the baseline physical therapy-assessed measure of function and endurance, namely the 6MWT, correlates with several critical short-term outcomes in CAR T patients with lymphoma. These include prolonged length of stay, survival at day 100, and there is suggested correlation with ORR, ICANS, and 30-day survival as well. These findings illustrate the potential for early recognition of deconditioned patients that may do poorly after CAR T-cell therapy. Identification of these patients could allow for therapeutic interventions prior to CAR T infusion or during their post-infusion hospital stay, designed to enhance their strength and endurance, and potentially improve these short-term outcomes. Prospective intervention studies are planned based on these findings.