ABSTRACT
Background: Patients with relapsed or refractory (R/R) LBCL after first-line treatment who are unable to undergo high-dose chemotherapy (HDCT) and hematopoietic stem cell transplantation (HSCT) hae poor outcomes and limited treatment options. Aims: PILOT (NCT03483103) ealuated liso-cel, an autologous, CD19-directed chimeric antigen receptor (CAR) T cell product, as second-line treatment in patients with R/R LBCL not intended for HSCT. Methods: Eligible patients were adults with R/R LBCL after first-line treatment who were not deemed candidates for HDCT and HSCT by their physician and met ≥ 1 frailty criteria as follows: age ≥ 70 years, Eastern Cooperatie Oncology Group performance status (ECOG PS) of 2, diffusing capacity for carbon monoxide ≤ 60%, left entricular ejection fraction < 50%, creatinine clearance < 60 mL/min, or alanine aminotransferase/aspartate aminotransferase > 2 × the upper limit of normal. Bridging therapy was allowed. Patients receied lymphodepletion with cyclophosphamide and fludarabine, followed 2-7 days later by liso-cel infusion at a target dose of 100 × 106 CAR+ T cells. Cytokine release syndrome (CRS) was graded per Lee 2014 criteria. Neurological eents (NE) were defined as inestigator-identified neurological aderse eents related to liso-cel and graded using the National Cancer Institute Common Terminology Criteria for Aderse Eents, ersion 4.03. The primary endpoint was objectie response rate (ORR) per independent reiew committee;all patients had ≥ 6 months of follow-up from first response. Results: Of 74 patients who underwent leukapheresis, 61 receied liso-cel and 1 receied nonconforming product (ie, product wherein one of the CD8 or CD4 cell components did not meet one of the requirements to be considered lisocel). Common reasons for preinfusion dropout included death and loss of eligibility (5 each). For liso-cel-treated patients, median age was 74 years (range, 53-84;79% ≥ 70 years) and 69%, 26%, and 5% met 1, 2, and 3 frailty criteria, respectiely;26% had ECOG PS of 2 and 44% had Hematopoietic Cell Transplantation-specific Comorbidity Index score ≥ 3. After first-line treatment, 54% were chemotherapy refractory, 21% relapsed within 12 months, and 25% relapsed after 12 months;51% of patients receied bridging chemotherapy. Median (range) onstudy follow-up was 12.3 months (1.2-26.5). ORR and complete response rate were 80% and 54%, respectiely (Table). Median duration of response and progression-free surial were 12.1 months and 9.0 months, respectiely. Median oerall surial has not been reached. The most frequent treatment-emergent aderse eents (TEAE) were neutropenia (51%), fatigue (39%), and CRS (38%), with grade 3 CRS in 1 patient (2%) and no grade 4/5 CRS eents. Any-grade NEs were seen in 31% (n = 19) of patients;grade 3 NEs occurred in 5% (n = 3) of patients and no grade 4/5 NEs were reported. Seen percent (n = 4) receied tocilizumab only, 3% (n = 2) receied corticosteroids only, and 20% (n = 12) receied both tocilizumab and corticosteroids for treatment of CRS and/or NEs. Oerall, grade ≥ 3 TEAEs occurred in 79% (n = 48) of patients, with grade 5 TEAEs in 2 patients (both due to COVID-19). Two patients (3%) had grade 3/4 infections and 15 (25%) had grade ≥3 neutropenia at Day 29. Summary/Conclusion: In the PILOT study, liso-cel as second-line treatment in patients with LBCL who met ≥ 1 frailty criteria and for whom HSCT was not intended demonstrated substantial and durable oerall and complete responses, with no new safety concerns. (Table Presented).
ABSTRACT
Background: Pts with R/R LBCL after first-line (1L) treatment (tx) who are unable to undergo high-dose chemotherapy (HDCT) and HSCT have poor outcomes and limited tx options. PILOT (NCT03483103) evaluated liso-cel, an autologous, CD19-directed chimeric antigen receptor (CAR) T cell product, as 2L tx in pts with R/R LBCL not intended for HSCT. Methods: Eligible pts were adults with R/R LBCL after 1L tx who were not deemed candidates for HDCT and HSCT by their physician and met ≥ 1 frailty criteria: age ≥ 70 yr, ECOG PS = 2, DLCO ≤ 60%, LVEF < 50%, CrCl < 60 mL/min, or ALT/AST > 2 × ULN. Bridging tx was allowed. Pts received lymphodepletion with cyclophosphamide and fludarabine, followed 2-7 days later by liso-cel at a target dose of 100 × 106 CAR+ T cells. Cytokine release syndrome (CRS) was graded per Lee 2014 criteria and neurological events (NE) per NCI CTCAE, version 4.03. Primary endpoint was ORR per independent review committee (IRC);all pts had ≥ 6 mo followup (f/u) from first response. Results: Of 74 pts leukapheresed, 61 received liso-cel and 1 received nonconforming product. Common reasons for pre-infusion dropout included death and loss of eligibility (5 each). For liso-cel-treated pts, median age was 74 yr (range, 53-84;79% ≥ 70 yr) and 69%, 26%, and 5% met 1, 2, and 3 frailty criteria, respectively;26% had ECOG PS = 2 and 44% had HCT-CI score ≥ 3. After 1L tx, 54% were chemotherapy refractory, 21% relapsed ≤ 12 mo, and 25% relapsed > 12 mo;51% of pts received bridging chemotherapy. Median (range) on-study f/u was 12.3 mo (1.2-26.5). ORR and CR rate was 80% and 54%, respectively. Median DOR and PFS was 12.1 mo and 9.0 mo, respectively. Median OS has not been reached (Table). Most frequent tx-emergent AEs (TEAE) were neutropenia (51%), fatigue (39%), and CRS (38%), with grade (gr) 3 CRS in 1 pt (2%) and no gr 4/5 CRS. Any-grade NEs were seen in 31%, gr 3 in 5% (n = 3), and no gr 4/5 NEs;7% received tocilizumab, 3% corticosteroids, and 20% both for tx of CRS/NEs. Overall, gr ≥ 3 TEAEs occurred in 79%, with gr 5 in 2 pts (both due to COVID-19). Two pts (3%) had gr 3/4 infections and 15 (25%) had gr ≥3 neutropenia at Day 29. Conclusions: In the PILOT study, liso-cel as 2L tx in pts with LBCL who met ≥ 1 frailty criteria and for whom HSCT was not intended demonstrated substantial and durable overall and complete responses, with no new safety concerns.