Axicabtagene ciloleucel is an autologous anti-CD19 CAR T cell therapy indicated for the treatment of Relapsed/Refractory (R/R) large B-cell lymphoma and follicular lymphoma (FL), both after ≥ 2 lines of systemic therapy. This study presents data with patients with relapsed/refractory indolent non-Hodgkin’s Lymphoma (R/R iNHL)
During the 63rd ASH Annual Meeting & Exposition, updated data from ZUMA-5 (NCT03105336), a phase 2, multicenter, single-arm study, evaluating axicabtagene ciloleucel (axi-cel) in patients with relapsed/refractory indolent non-Hodgkin’s Lymphoma (R/R iNHL) were presented, including follicular lymphoma (FL) and marginal zone lymphoma (MZL). In the primary analysis of the study (N = 104; 17.5-month follow-up), the overall response rate (ORR) was 92% (complete response rate [CR] = 76%) and median peak CAR T-cell levels were numerically higher in patients with FL who were in continuous response at cut-off than in those who relapsed.
Adult patients with R/R iNHL after ≥ 2 lines of therapy (including an anti-CD20 monoclonal antibody plus an alkylating agent) underwent leukapheresis and conditioning chemotherapy, followed by a single infusion of axi-cel at 2×106 CAR T cells/kg. The primary endpoint was centrally assessed ORR per Lugano classification. The updated efficacy analysis occurred when more than 80 patients treated for FL were followed for more than 2 years post-infusion, including patients with MZL who had ≥ 4 weeks of post-infusion follow-up.
As of March 31st, 2021, 149 patients with iNHL (124 FL; 25 MZL) were treated with axi-cel. Of these, 110 patients (86 FL; 24 MZL) were eligible for efficacy analyses. Among those with FL, the mean follow-up was 30.9 months. The centrally assessed ORR was 94% in patients with FL (79% CR rate).
At the cut-off, 57% of eligible patients with FL had sustained responses, with 68% of those who achieved CR developing sustained responses. The estimated duration of response (DOR) and median progression-free survival (PFS) were 38.6 months and 39.6 months in patients with FL, respectively.
Among patients with LF who progressed less than 2 years after initial chemo-immunotherapy (n = 49), the median DOR was 38.6 months. On the other hand, the median DOR was not achieved for those who did not progress within 2 years (n = 29).
The median PFS in patients with FL who had progression in the first 2 years was 39.6 months, while the median PFS was not reached in those without progression in this period.
The median time to next treatment (TTNT) was 39.6 months in all eligible patients with FL. The median overall survival (OS) was not reached, with an estimated 24-month OS rate of 81%.
Among eligible patients with MZL, the median follow-up was 23.8 months. ORR was 83% (50% maintained sustained response), 63% with CR (73% with sustained response). Medians for DOR and TTNT were not achieved in patients with MZL and the 24-month rates were, respectively, “unestimated” and 51%. The median PFS was 17.3 months and the median OS was not achieved (70% OS rate at 24 months).
Common grade ≥ 3 adverse events (AEs) in all iNHL-treated patients were consistent with previous reported: neutropenia (33%) and anemia (25%). Grade ≥ 3 cytopenias present for more than 30 days post-infusion were reported in 34% of patients with iNHL (33% FL; 36% MZL). Consistent with previous reported, grade ≥ 3 cytokine release syndrome and neurologic events occurred in 7% of participants (6% FL; 8% MZL) and 19% (15% FL; 36% MZL), respectively. Most cases of cytokine release syndrome (120/121) and neurologic events (82/87) of any degree resolved by data cut.
Among FL patients who had evaluable samples, 76% (65/86) had detectable CAR gene-marked cells at low levels by 12 months after infusion; 53% (23/43) had detectable cells 24 months after infusion.
Among evaluable patients with MZL, 67% (8/12) had detectable CAR gene-marked cells 12 months after infusion; 60% (3/5) had detectable cells 24 months after infusion. B cell reconstitution was detectable in 59% of evaluable patients with FL (49/83) and 42% of those with MZL (5/12) at 12 months after infusion. At 24 months, B cells were detected in 61% of evaluable patients with FL (25/41) and 50% of those with MZL (2/4).
The authors conclude that after long-term follow-up in ZUMA-5, axicabtagene ciloleucel demonstrated substantial and continued benefit in iNHL patients. n FL, high response rates translated to durability, with a median DOR of 38.6 months and 57% of eligible patients in ongoing response at data cutoff. In MZL, efficacy outcomes appeared to improve with longer follow-up, with the median DOR and OS not yet reached. Axi-cel maintained a manageable safety profile, with no new safety signals.
1. Neelapu SS, et al. Long-Term Follow-up Analysis of ZUMA-5: A Phase 2 Study of Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed/Refractory (R/R) Indolent Non-Hodgkin Lymphoma (iNHL). The 63rd ASH Annual Meeting and Exposition. Abstract 93. 2021.