Outcomes of Outpatient CD19-Targeted Chimeric Antigen Receptor T-Cell Therapy in Relapsed or Refractory B-Cell Lymphomas: A Systematic Review and Meta-Analysis
Authors: Shahzad Moazzam , Noor Jawad , Amin Muhammad Kashif , Zaman Zubia , Akram Umar , Sharif Maryyam , Ali Hameer , Qayyum Uzma , Khan Muhammad Waqas , Shamoon Sheena , Pokhrel Bidushi , Khan Asim Ahmad , Habib Hira , Chaudhary Sibgha Gull , Anwar Iqra , Lutfi Forat , Shune Leyla O. , McGuirk Joseph P. , Mushtaq Muhammad Umair 
Published: December 2024

Background:
Chimeric Antigen Receptor (CAR) T-cell therapies targeting CD19 have shown high effectiveness for relapsed or refractory B-cell lymphomas. The recent interest in outpatient CAR T-cell infusion, aimed at reducing healthcare costs and eliminating the need for extended hospital stays, presents a promising future for B-cell lymphoma treatment. In this study, we aimed to investigate the outcomes after outpatient CD19-targeted CAR T-cell therapy in patients with B-cell lymphomas.
Methods:
As per the Preferred Reporting Items for Systemic Reviews and Meta-Analysis (PRISMA) guidelines, a comprehensive literature search was performed on three databases (PubMed, Cochrane, and Clinicaltrials.gov) using MeSH terms and keywords for 'Outpatient AND 'CAR-T OR 'Chimeric Antigen Receptor T-cell' from the date of inception to June 30, 2024. Our literature research produced 1357 articles. After excluding irrelevant and review articles during primary and secondary screening, six original studies reporting outcomes in outpatient CAR-T cell therapy were included. Analysis was done on R version 4.4.0 using “meta” and “metasens” packages. The inverse variance method on Freeman Tukey double arcsine transformed data was utilized. We then analyzed the pooled data using a random-effects model and assessed heterogeneity using I2. Confidence intervals were adjusted using the Hartung-Knapp adjustment, and Tau2 was estimated using the restricted maximum-likelihood estimator.
Results:
A total of 290 patients from 6 studies who received axi-cel (axicabtagene ciloleucel), tisa-cel (tisagenlecleucel), liso-cel (lisocabtagene maraleucel), and brexu-cel (brexucabtagene autoleucel), and reporting outcomes for relapsed and refractory B-cell lymphomas as outpatients were included. The most common indication for CAR T-cell therapy was diffuse large B-cell lymphoma in 69.3% (n=138/199), followed by follicular lymphoma in 14.5% (n=29/199) and mantle cell lymphoma in 10.5% (n=21/199) of patients. Two out of six studies reported using fludarabine and cyclophosphamide as lymphodepletion and a median of 3.5 (1-6) therapies prior to CAR T-cell therapy. Within 30 days of CAR T-cell infusion, 71.2% (114/163) of patients required hospitalization, and 5.4% (5/91) required ICU admission. The median length of hospitalization was six days (5-14), and the median time from CAR T-cell therapy to hospitalization was four days (range 3-5). Cytokine release syndrome and neurotoxicity were reported in 32.7% (90/290) and 15.8% (38/239) of patients, respectively. To manage adverse effects, 12.8% (34/265) received tocilizumab, 4.5% (12/265) received steroids, and 3.7% (10/265) received both. Overall mortality was 15.6% (25/160), and the most common cause of mortality was disease progression or relapse. The pooled overall response rate (ORR), complete response (CR), and partial response (PR) were 72% (95% CI 0.00-1.00, I2=45%, p=0.18, n=49), 50% (95% CI 0.11-0.88, I2 =53%, p=0.12, n=45), and 10% (95% CI 0.00-1.00, I2 =88%, p&lt;0.01, n=4), respectively.
Conclusion:
Outcomes comparable to previously published studies with inpatient CAR T-cell therapy were observed with outpatient administration of CAR T-cell therapy. Outpatient CAR T-cell therapy is feasible and safe and may reduce the healthcare burden of CD19-targeted CAR T-cell therapies for B-cell malignancies. Future studies are needed to validate these findings and compare outcomes after inpatient versus outpatient infusion of CAR T-cell therapy.