Outpatient Administration of Brexucabtagene Autoleucel (brexu-cel) for Acute Lymphoblastic Leukemia (ALL) and Mantle Cell Lymphoma (MCL) Is Safe and Feasible

Background

Brexu-cel has become an important treatment option for relapsed/refractory (R/R) MCL and B-cell ALL based on the ZUMA-2 and ZUMA-3 trials, respectively. While others have reported successful outpatient (OP) administration of chimeric antigen receptor (CAR) T-cell therapy, there is limited data with brexu-cel, which has higher reported rates of toxicity compared to other CAR T products. Here, we report our experience with lymphodepletion OP (LDOP) and brexu-cel infusion compared to those who received LD inpatient (LDIP).

Methods

We conducted a retrospective study of adult patients (pts) who received brexu-cel for B-ALL and MCL at City of Hope from 11/1/2020-3/31/2024. Pts were divided into 2 groups: those who initiated LDOP, irrespective of whether they received brexu-cel as an OP or IP; and those who initiated LDIP. The decision for administering LDOP vs LDIP was at the treating physician's discretion. The primary endpoint was day-60 non-relapse mortality (NRM), defined as death before day-60 after brexu-cel infusion that was not preceded by progressive disease, and were summarized using cumulative incidence estimates, where relapse/progression was viewed as a competing risk of NRM. To improve the comparability between the two groups, we applied propensity score nearest matching method (ratio 1, caliper = 0.1) using ECOG performance status, Severe4 comorbidity score, and bulky disease (bone marrow blasts ≥5% and/or presence of extramedullary or CNS disease) for B-ALL, or intermediate/high MIPIb for MCL at time of LD as the matching variables. The pts after matching constituted the sample for the outcomes analyses. Secondary endpoints were incidences of cytokine release syndrome (CRS), immune effector-cell associated neurotoxicity syndrome (ICANS), IP admission for LDOP pts, best complete response rate (CRR), and 6-month progression-free survival (PFS).

Results

A total of 69 pts received brexu-cel, including 34 LDOP pts and 35 LDIP pts. Of the 34 LDOP pts 6 were admitted prior to brexu-cel infusion: 3 were planned admissions, and 3 were admitted for disease-related complications including fever (n=2) and intractable pain (n=1). Notable differences between the two groups were that LDOP pts were treated more recently; more likely to be male; have lower ECOG; and have fewer prior lines of systemic therapies. After matching, the final sample included in the outcome analyses consisted of 56 pts (LDIP: 17 B-ALL and 11 MCL pts; LDOP: 20 B-ALL and 8 MCL pts). The distribution of ECOG, severe comorbidities (Severe4 comorbidity index ≥1), and bulky disease for B-ALL or MIPIb for MCL at LD was balanced. Among the 56 matched pts, the median length of follow-up among survivors was 6.5 months (range: 1.5-42.3) post-brexu-cel infusion. The 60-day NRM was 7.1% (95%CI: 1.2-21%) in the LDIP group and 3.6% (95%CI: 0.25-16%) in the LDOP group. Three pts (2 in LDIP, 1 in LDOP) experienced NRM events within 60 days due to hemophagocytic lymphohistiocytosis, bacteremia, and fungal infection, respectively. No differences were observed in any grade CRS and grade ≥3 CRS, 82% vs 86% (P >0.9) and 14% vs 7.1% (P=0.7), and in any grade ICANS and grade ≥3 ICANS, 61% vs 54% (P=0.6) and 25% vs 29% (P=0.8), respectively. While both groups had similar receipt of prophylactic steroid (25% LDIP vs 32% LDOP, P=0.6), more LDOP pts received prophylactic anakinra (29% vs 7%, P=0.078). The median length of hospitalization during the first 100 days were 27 days (range: 13 - 47) for the LDIP group and 10 days (range: 0 - 52) the LDOP group (P<0.001). Twenty-four LDOP patients (86%) were admitted at a median of 8 days (range: 1 - 17) from LD initiation. Nineteen patients (79%) were admitted for brexu-cel-related toxicity: 17 for CRS, 1 for hypotension due to poor oral intake, and 1 for dyspnea; 3 were scheduled admission due to bulky disease, 1 was admitted for fever and 1 for pain control during LD due to the underlying malignancy. The best CR rate for MCL was 73% (95%CI: 39-94%) in LDIP and 75% (35-97%) in LDOP, and for B-ALL was 88% (64-99%) and 90% (68-99%), respectively. The 6-month PFS for the LDIP and LDOP pts were 74% (95% CI: 51-88) and 87% (95%CI: 64-96%), respectively. Additional data regarding efficacy, hospital resource utilization, and toxicities will be presented at the meeting.

Conclusion

Brexu-cel is safe to administer OP with similar efficacy and NRM. Future studies with larger sample size and longer follow-up are needed to confirm our findings.

Baird:Kite Pharma-Gilead: Honoraria, Research Funding; Cargo Therapeutics: Research Funding; Janssen Pharma: Research Funding; Genentech-Roche: Research Funding; Regeneron Pharma: Research Funding. Aldoss:Kite Pharma: Other: consulting fees; Pfizer: Honoraria, Other: consulting fees; Takeda Pharmaceuticals: Other: consulting fees; Jazz Pharmaceuticals: Other: consulting fees; Sobi: Other: consulting fees; AbbVie: Other: research support; Syndax Pharmaceuticals, Inc.: Other: consulting fees; Amgen: Honoraria, Other: consulting fees. Danilov:AstraZeneca: Consultancy, Research Funding; AbbVie: Consultancy; BeiGene: Consultancy; Genentech: Consultancy; Nurix: Consultancy, Research Funding; MorphoSys: Consultancy; Incyte: Consultancy; TG Therapeutics: Consultancy, Research Funding; Bayer: Consultancy, Research Funding; Takeda: Research Funding; MEI Pharma: Research Funding; ADCT: Consultancy; Bristol Meyers Squibb: Consultancy, Research Funding; Cyclacel: Research Funding; GenMab: Consultancy, Research Funding; Janssen: Consultancy. Phillips:Pharmacyclics: Consultancy; AbbVie: Research Funding; Lymphoma & Myeloma Connect: Honoraria; ADC Therapeutics: Consultancy; TG Therapeutics: Consultancy; Genmab: Consultancy; Celgene: Consultancy; Kite/Gilead: Consultancy; Curis: Consultancy; Gilead Sciences: Consultancy; Bayer: Consultancy, Research Funding; Genentech: Consultancy; Incyte: Consultancy; Pharmacyclics/Janssen: Research Funding; Seattle Genetics: Consultancy, Honoraria. Sandhu:Autolus: Consultancy. Mei:Novartis: Consultancy; Synethkine: Consultancy; SeaGen: Consultancy, Speakers Bureau; ADC Therapeutics: Consultancy; AstraZeneca: Consultancy; BMS: Research Funding; Incyte: Research Funding; Beigene: Research Funding; Genentech: Research Funding. Koller:Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees; Ascentage: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Forman:Allogene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Lixte Bio: Consultancy, Membership on an entity's Board of Directors or advisory committees. Budde:AstraZeneca, Mustang Therapeutics, Merck: Research Funding; ADC Therapeutics, AstraZeneca, AbbVie, F. Hoffmann-La Roche Ltd, Genentech, Inc., Genmab, Jenssen, Regeneron: Consultancy. Aribi:Seagen: Consultancy; Kite, a Gilead Company: Consultancy.