Earlier Steroid Use with Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed/Refractory Large B Cell Lymphoma

• Published in: Blood 2019-11, Vol.134 (Supplement_1), p.243-243
• Main Authors: Topp, Max, Van Meerten, Tom, Houot, Roch, Minnema, Monique C., Milpied, Noel, Lugtenburg, Pieternella J., Thieblemont, Catherine, Wermke, Martin, Song, Kevin, Avivi, Irit, Kuruvilla, John, Dührsen, Ulrich, Chu, Rachel, Zheng, Lianqing, Plaks, Vicki, Kerber, Anne, Kersten, Marie Jose'
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2019-126081

Background: Axi-cel is an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy approved for the treatment (Tx) of patients (pts) with relapsed/refractory large B cell lymphoma (R/R LBCL) with ≥ 2 prior systemic therapies. In Cohorts 1+2 (C1+2) of ZUMA-1, the multicenter, single-arm, registrational Phase 1/2 study of axi-cel in pts with refractory LBCL, Grade ≥ 3 cytokine release syndrome (CRS) and neurologic events (NEs) occurred in 11% and 32% of pts, respectively (Locke FL et al, Lancet Oncol 2019). In C1+2, the objective response rate (ORR) was 83%, the complete response (CR) rate was 58%. A non-randomized safety expansion cohort was added (Cohort 4 [C4]) to evaluate the effect of earlier steroid use on the rates of CRS and NEs. Initial results suggested that early use of steroids may help reduce the incidence of severe CRS and NEs without affecting response rates or CAR T cell expansion (Topp MS et al, ASCO 2019). Here we present the primary analysis of ZUMA-1 C4 with a greater number of pts and longer follow-up (F/U). Methods: Eligible pts were leukapheresed, could receive optional bridging chemotherapy (not allowed in C1+2), and received conditioning chemotherapy (fludarabine and cyclophosphamide) prior to axi-cel infusion at a target dose of 2 × 106 anti-CD19 CAR T cells/kg. Patients in C4 received early steroid intervention starting at Grade 1 NE and at Grade 1 CRS when no improvement was observed after 3 days of supportive care. The primary endpoints were incidence and severity of CRS and NE. Additional endpoints were efficacy outcomes and biomarker analyses, including levels of CAR T cells and inflammatory markers in blood. ORR and CAR T cell levels in C1+2 and 4 were compared across quartiles of tumor burden, the values of which were determined by C1+2. Results: As of May 6, 2019, 41 pts had received axi-cel, with a median F/U of 8.7 mo (range, 2.9 - 13.9 mo). Only 1 pt had not reached ≥ 6 mo of F/U due to a delay in dosing after the primary analysis trigger. Pts who received bridging therapy prior to axi-cel (68%) all had evidence of disease after bridging, documented by a new baseline PET/CT scan. The median age was 61 years (range, 19 - 77 years; 32% ≥ 65 years), and 68% were male. Disease types varied and included DLBCL (63%), TFL (24%), PMBCL (5%), HGBCL (7%). Nearly half of all pts (49%) had an ECOG 1, 70% had disease stage III/IV, 68% were refractory to ≥ 2nd-line therapy, 12% were relapsed to ≥ 2nd-line therapy, 63% had ≥