Axi-cel more effective but tisa-cel less toxic in DLBCL

In a matched set population of patients with diffuse large B-cell lymphoma (DLBCL) who had received ≥2 lines of treatment, axicabtagene ciloleucel (axi-cel) resulted in a significantly prolonged progression-free survival (PFS) compared with tisagenlecleucel (tisa-cel). However, axi-cel was associated with significantly more frequent grade ≥3 neurotoxicity compared with tisa-cel. These results could help refine specific patient sub-populations who benefit most from each type of CAR T-cell therapy.

Axi-cel and tisa-cel are autologous anti-CD19 CAR T-cell therapies approved in the US and EU for adults with relapsed/refractory (R/R) DLBCL after ≥2 lines of systemic therapy. Dr Emmanuel Bachy (Hospices Civils de Lyon, France) and others conducted a propensity score-matched comparison of axi-cel and tisa-cel in a large cohort of R/R DLBCL patients treated outside of clinical trials. After a 1:1 ratio propensity score-matching, therapy outcomes were compared between 144 patients treated with axi-cel and 144 patients treated with tisa-cel. The primary endpoint was overall survival (OS).

After a median follow-up of 6.6 months, OS was not significantly different between axi-cel and tisa-cel at 6 months (78% vs 70% respectively; P=0.44; see Figure). Best overall and complete response rates were significantly higher with axi-cel compared with tisa-cel (73% vs 60%; P=0.02; and 56% vs 36%; P<0.001, respectively). At 6 months, PFS was significantly longer with axi-cel than with tisa-cel (53% vs 32%; P=0.011).

Figure: Overall survival with tisa-cel versus axi-cel [1]



Axi-cel, axicabtagene ciloleucel; OS, overall survival; tisa-cel, tisagenlecleucel.

With respect to the toxicity profile, there was no significant difference in the incidence of cytokine release syndrome (CRS), but axi-cel was associated with significantly more frequent neurotoxicity (ICANS) compared with tisa-cel, namely:

• 6% vs 18.1% for grade 1–2 ICANS; and
• 4% vs 2.1% for grade ≥3 ICANS (P<0.001).

After stringent propensity score-matching on a large patient population treated with CAR T-cell therapy, axi-cel resulted in higher response rates and significantly prolonged PFS compared with tisa-cel. However, greater efficacy came at the cost of higher neurotoxicity with axi-cel.

1. Bachy E, et al. A Propensity Score-Matched Comparison of Axi-Cel and Tisa-Cel for Relapsed/Refractory Diffuse Large B-Cell Lymphoma in Real-Life: A Lysa Study from the Descar-T Registry. Abstract 92, ASH 2021 Annual Meeting, 11–14 December.

 

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Posted on 4 February, 20224 February, 2022