OUTREACH: phase 2 study of lisocabtagene maraleucel as outpatient or inpatient treatment at community sites for R/R LBCL

Abstract

Lisocabtagene maraleucel (liso-cel) is an autologous, CD19-directed, 4-1BB chimeric antigen receptor (CAR) T-cell product approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). We present the OUTREACH primary analysis, evaluating the safety and efficacy of outpatient monitoring after liso-cel treatment at community sites in the United States. Adults with R/R LBCL after ≥2 prior lines of therapy received liso-cel. Outpatient vs inpatient monitoring was per investigator discretion. The primary end points were incidences of grade ≥3 cytokine release syndrome (CRS), neurological events (NEs), prolonged cytopenia, and infections. Efficacy was a secondary end point. Eighty-two patients received liso-cel (outpatient monitored, 70%; inpatient monitored, 30%). The median follow-up was 10.6 months (range, 1.0-24.5). In outpatients and inpatients, grade ≥3 CRS occurred in 0% and 0%, NEs in 12% and 4%, infections in 12% and 8%, and prolonged cytopenia in 33% and 32%, respectively. Among outpatients, 25% were never hospitalized after infusion, and 32% were hospitalized ≤72 hours after the day of infusion; the median time to hospitalization was 5.0 days (range, 2-310). The median initial hospitalization duration after liso-cel was 6.0 days (range, 1-28) for outpatients and 15.0 days (range, 3-31) for inpatients. Objective response rate was 80%, complete response rate was 54%, and the median duration of response was 14.75 months (95% confidence interval, 5.0 to not reached). OUTREACH is, to our knowledge, the first and largest study to prospectively assess CAR T-cell therapy with outpatient monitoring in community-based medical centers. Liso-cel demonstrated meaningful efficacy with favorable safety in patients with R/R LBCL. Data support the feasibility of liso-cel administration at community sites with outpatient monitoring. This trial was registered at www.ClinicalTrials.gov as #NCT03744676.

Graphical abstract

Figure 1.

Outpatient requirements in OUTREACH. (A) Outpatient CAR T-cell treatment. Patients were considered to be monitored as outpatients if liso-cel was administered in the outpatient facility or in the inpatient facility with subsequent discharge the same day at the end of the observation period. (B) Site and patient requirements.

Figure 2.

CONSORT diagram (intention-to-treat set). ∗Screen failures due to not meeting eligibility criteria included not having an eligible R/R LBCL histology (n = 6), social/familial/geographical conditions (n = 5), not having PET-positive disease (n = 3), not signing the informed consent form before study procedures (n = 1), not having adequate cardiac function (n = 1), history of cardiovascular condition (n = 1), and receipt of radiation within 6 weeks of leukapheresis (n = 1). †One patient did not meet 2 eligibility criteria (ECOG PS of 0-1 and inadequate renal function). ‡NCP was defined as any CAR T-cell product wherein one of the CD8 or CD4 cell components did not meet 1 of the requirements to be considered liso-cel but could be considered appropriate for infusion. The patient who received NCP (CD8 component was out of specifications) was not included in the safety/efficacy analysis. ECOG PS, Eastern Cooperative Oncology Group performance status; NCP, nonconforming product; PD, progressive disease; PI, principal investigator.

Figure 3.

DOR, PFS, and OS (liso-cel–treated set). (A-C) Kaplan-Meier estimates of DOR (A), PFS (B), and OS (C). ∗Kaplan-Meier method was used to obtain 2-sided 95% CIs. †Reverse Kaplan-Meier method was used to obtain median follow-up and its 95% CIs.