Real-World Liso-Cel Nonconforming Product Efficacy and Safety Aligns With R/R LBCL Pivotal Trials


The data comes from an expanded access protocol (EAP; JCAR017-EAP-001) that included 96 patients in total who were treated with the nonconforming product.

Nonconforming product (NCP) of lisocabtagene maraleucel (liso-cel; Breyanzi; Bristol Myers Squibb), which is a CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy currently marketed in the United States and European Union for relapsed/refractory (r/r) large B-cell lymphoma indications, has demonstrated efficacy and safety in line with pivotal trial results in patients with r/r LBCL treated in an expanded access protocol (EAP; JCAR017-EAP-001). The data were presented in a poster at the 2024 Tandem Meetings |Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, held in San Antonio, Texas, February 21-24, 2024.

Paolo Caimi, MD, of Taussig Cancer Center, and colleagues defined NCP liso-cel as liso-cel product with CD8+ and/or CD4+ cell components that do not meet at least 1 of the commercial release specifications, but did meet the EAP’s clinical release criteria. The EAP included 96 patients in total who were treated with NCP. Among 92 patients who were evaluable for overall response rate (ORR), the ORR was 73% (95% CI, 63%-82%) and the complete response rate was 63% (95% CI, 52%-73%). The median duration of response (DOR) for all patients who responded and had available DOR data was 9.5 months (95% CI, 7.4 to not reached) (total at risk, N = 66) and the median progression free survival (PFS) for all patients who responded and had available PFS data was 8.3 months (95% CI, 5.1 to 11.3) (total at risk, N = 91). Among patients with available overall survival (OS) data the median OS was not reached (95% CI, 8.9 to not reached) (total, N = 96).

In terms of safety, 45 of 96 patients (47%) experienced cases of cytokine release syndrome (CRS). This included 2 patients (2%) who experienced grade 4 CRS cases. There were no grade 3 CRS cases. Immune effector cell-associated neurotoxicity syndrome (ICANS) cases were reported in 21 patients (22%). This included 7 patients (7%) who experienced grade 3 ICANS cases and 1 patient (1%) who experienced a grade 4 ICANS case. Other adverse events deemed to be of special interest included prolonged cytopenia (17 patients, 18%); clinically significant infections (41 patients, 43%); grade 3 or grade 4 tumor lysis syndrome (1 patient, 1%); grade 3 or grade 4 organ toxicity (6 patients, 6%); and secondary primary malignancy (4 patients, 4%). There were 34 deaths reported in the EAP, with 24 attributed to the primary disease, 3 attributed to unidentified infections, 2 attributed to pulmonary failure, 2 attributed to viral infections, 1 attributed to bacterial infection, 1 attributed to COVID-19 infection, and 1 attributed to an unprovided cause.

Among the 96 patients treated in the EAP, 55 were men and 41 were women. The ages of the patients ranged from 29 to 87 years (median, 69.5). The histological makeup of the population constituted 73 patients with diffuse LBCL, 1 patient with primary mediastinal B-cell lymphoma, 15 patients with high-grade B-cell lymphoma, and 4 patients with other B-cell lymphoma(s). The population included 52 patients with comorbidities and 4 patients with central nervous system involvement of their disease. The number of prior lines of systemic therapy received by the patients in the EAP ranged from 0 to 9 (median, 3); furthermore, 76 patients (79%) had received at least 2 lines of prior systemic therapy. Seventeen of the 96 patients had previously been treated with hematopoietic stem cell transplant (HSCT); this included 14 patients who received autologous HSCT, 1 patient who received allogeneic HSCT, and 2 patients whose HSCT was not specified as autologous or allogeneic. Bridging therapy for disease control was administered to 35 of the patients in the EAP.

“This is the first large, postmarketing study of patients who received liso-cel NCP in the United States,” Caimi and colleagues concluded. “Outcomes in a broad population of patients with r/r LBCL who received liso-cel NCP demonstrated efficacy benefits and safety consistent with liso-cel pivotal studies. The probability of survival at 12 months was 55%. The incidences of grade 3 or higher CRS and ICANS were 2% and 8% respectively, which are similar to reports using conforming product. No new safety signals were detected with infusion of NCP. These real-world data provide additional important information to support clinical decision-making for the treatment of patients with r/r LBCL.”

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1. Caimi P, Schuster SJ, Nastoupil LJ, et al. Outcomes in patients (pts) with R/R large b-cell lymphoma (LBCL) who received nonconforming product (NCP) to commercial release oflisocabtagenemaraleucel(liso-cel) in the United States (US). Presented at: 2024 Tandem Meetings, February 21-24, San Antonio, Texas. Abstract #244
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