Results from Outreach: A Phase 2 Study of Lisocabtagene Maraleucel (Liso-cel) Administered As Outpatient (Outpt) or Inpatient (Inpt) Treatment in the Community/Nonuniversity Setting in Patients (Pts) with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL)

Background: CAR T cell therapies are generally administered in inpt settings owing to concerns of AE management. Prospective data on treatment and outcomes with CAR T cell therapy, encompassing infusion and outpt monitoring, in community settings is of interest. Liso-cel is an autologous, CD19-directed, 4-1BB CAR T cell product administered at equal target doses of CD8⁺ and CD4⁺ CAR⁺ T cells. In TRANSCEND NHL 001 (NCT02631044) in pts with third-line or later LBCL, liso-cel showed meaningful efficacy (ORR, 73%; CR rate, 53%) and a manageable safety profile (grade [gr] ≥ 3 cytokine release syndrome [CRS], 2%; gr ≥ 3 neurological events [NE], 10%; gr ≥ 3 prolonged cytopenia, 37%; gr ≥ 3 infections, 12%) (Abramson et al. Lancet 2020). Here we present an update from OUTREACH (NCT03744676), which evaluated liso-cel in pts with R/R LBCL (a population similar to TRANSCEND NHL 001) across outpt and inpt settings at community sites in the United States. The primary analysis (PA) will be presented at the meeting.

Methods: Adults with R/R PET-positive LBCL after ≥ 2 lines of therapy and ECOG PS ≤ 1 were enrolled at community sites. Pts with gr 3‒4 cytopenias, mild-moderate organ dysfunction (LVEF ≥ 40%; serum CrCl > 30 mL/min), secondary CNS lymphoma, and prior autologous HSCT were eligible. After leukapheresis and lymphodepleting chemotherapy (LDC), pts received liso-cel at a target dose of 100 × 10⁶ CAR⁺ T cells. Outpt versus inpt monitoring was at the investigator's discretion. Primary endpoint (safety) was incidence of gr ≥ 3 CRS, NEs, prolonged cytopenias (Day 29 gr ≥ 3 laboratory values), and infections. Secondary endpoints included safety, ORR, CR rate, duration of response (DOR), and PFS. CRS was graded per Lee 2014 criteria. Study sites had a multidisciplinary CAR T cell therapy team and standard operating procedures (SOP) for outpt monitoring of toxicity and admission for CRS/NE management. Pts had to have a caregiver and stay ≤ 1 h travel time to study site.

Results: At data cutoff, 79 pts received liso-cel at community sites, with 66%/34% at FACT/non-FACT sites, including CAR T-inexperienced sites; 54 (68%) pts were monitored as outpts and 25 (32%) as inpts. Median age was 66 y (range, 28‒86; ≥ 65 y, 53%); 61% of pts had DLBCL NOS, 68% had screening ECOG PS 1, and 3% had secondary CNS lymphoma. Pts received a median of 2 prior lines of systemic therapy (range, 2‒6), 34% had ≥ 3 prior therapies, 82% were chemotherapy refractory, and 53% received bridging therapy. 28% had LDH ≥ 500 U/L and 38% had sum of the product of perpendicular diameters (SPD) ≥ 50 cm² before LDC. Most common reasons for inpt monitoring (n = 25) were disease characteristics (40%), investigator decision (32%), distance from site (12%), or no caregiver support (8%).

Most common treatment-emergent AEs were neutropenia (68%), leukopenia (44%), CRS (39%), thrombocytopenia (35%), anemia (33%), and fatigue (30%). No gr ≥ 3 CRS was reported. Any-grade NEs occurred in 30% (gr 3‒4, 10%). 28% of pts received tocilizumab and/or corticosteroids for CRS or NEs (Table). In outpts and inpts, respectively, any-grade CRS was reported in 37% and 44%, NEs in 30% and 32% (gr ≥ 3 in 13% and 4%), infections in 33% and 32% (gr ≥ 3 in 13% and 4%) and gr ≥ 3 prolonged cytopenias in 33% and 32%. For outpts, 24% were never hospitalized after infusion, 31% were hospitalized ≤ 4 days after infusion, and median time to hospitalization was 5.0 (range, 2‒310) days. Reasons for admission were AEs (63%) and other (13%). Two (4%) outpts were admitted to ICU during initial hospital stay (median [range] time in ICU, 3.5 [2‒5] days). Median (range) duration of initial hospital stay after liso-cel was 6.0 (1‒28) days (n = 41) for outpts and 13.0 (1‒31) days (n = 25) for inpts.

All pts were efficacy evaluable. ORR was 80% (CR rate, 52%) (Table). Longer follow-up, DOR, and PFS will be presented for the PA.

Conclusions: Pts with R/R LBCL treated with liso-cel were successfully infused and monitored as outpts in the community setting using SOPs and multidisciplinary teams. Liso-cel demonstrated clinical activity with a manageable safety profile in both outpts and inpts regardless of prior HSCT. 24% of outpts were never hospitalized after liso-cel infusion and only 31% were hospitalized ≤ 4 days after infusion. These data, along with shorter hospital stays in outpts vs inpts, suggest CAR T cell therapy costs could be reduced by outpt monitoring at qualified sites. The data support liso-cel monitoring at community sites and in the outpt setting.

Linhares:TG therapeutics: Other: advisory board; glaxosmithkline: Other: advisory board; ADC therapeutics: Other: advisory board, Research Funding; Gilead Sciences, Inc.: Other: advisory board; BeiGene USA, Inc.: Other: advisory board, Research Funding; Seagen Inc: Other: advisory board, Research Funding; Bristol Myers Squibb: Other: advisory board, Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Other: advisory board; Kyowa Kirin: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Curio Science: Other: Workshop Participation and Moderation. Cherry:BMS: Other: Ad Board. Varela:Kite/Gilead: Speakers Bureau; NexImmune: Consultancy, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees. Essell:Gilead: Speakers Bureau; BMS: Speakers Bureau. Fanning:BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genentech: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Yimer:Sanofi: Speakers Bureau; Pharmacyclics: Speakers Bureau; Karyopharm: Consultancy, Divested equity in a private or publicly-traded company in the past 24 months, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Speakers Bureau; epizyme: Divested equity in a private or publicly-traded company in the past 24 months; Beigene: Other: TRAVEL, ACCOMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding, Speakers Bureau; Janssen: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding, Speakers Bureau; Takeda: Research Funding, Speakers Bureau; GlaxoSmithKline: Speakers Bureau; Amgen: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Speakers Bureau; AstraZeneca: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Speakers Bureau; Texas Oncology: Current Employment. Sharman:Merck: Consultancy; Lilly: Consultancy, Honoraria, Research Funding; Araris Biotech AG: Consultancy, Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Consultancy, Honoraria, Research Funding; Pharmacyclics LLC, an AbbVie Company: Honoraria; Beigene: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Research Funding; Genentech: Consultancy; TG Therapeutics: Consultancy, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding. Vedal:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Mailley:Brisol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Espinola:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Mattar:Gilead: Speakers Bureau; Takeda: Speakers Bureau.