A real-world comparison of tisagenlecleucel and axicabtagene ciloleucel CAR T cells in relapsed or refractory diffuse large B cell lymphoma

Abstract

Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) have both demonstrated impressive clinical activity in relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL). In this study, we analyzed the outcome of 809 patients with R/R DLBCL after two or more previous lines of treatment who had a commercial chimeric antigen receptor (CAR) T cells order for axi-cel or tisa-cel and were registered in the retrospective French DESCAR-T registry study (NCT04328298). After 1:1 propensity score matching (n = 418), the best overall response rate/complete response rate (ORR/CRR) was 80%/60% versus 66%/42% for patients treated with axi-cel compared to tisa-cel, respectively (P < 0.001 for both ORR and CRR comparisons). After a median follow-up of 11.7 months, the 1-year progression-free survival was 46.6% for axi-cel and 33.2% for tisa-cel (hazard ratio (HR) = 0.61; 95% confidence interval (CI), 0.46–0.79; P = 0.0003). Overall survival (OS) was also significantly improved after axi-cel infusion compared to after tisa-cel infusion (1-year OS 63.5% versus 48.8%; HR = 0.63; 95% CI, 0.45–0.88; P = 0.0072). Similar findings were observed using the inverse probability of treatment weighting statistical approach. Grade 1–2 cytokine release syndrome was significantly more frequent with axi-cel than with tisa-cel, but no significant difference was observed for grade ≥3. Regarding immune effector cell-associated neurotoxicity syndrome (ICANS), both grade 1–2 and grade ≥3 ICANS were significantly more frequent with axi-cel than with tisa-cel. In conclusion, our matched comparison study supports a higher efficacy and also a higher toxicity of axi-cel compared to tisa-cel in the third or more treatment line for R/R DLBCL.

The place of allogeneic stem cell transplantation in aggressive B-cell non-Hodgkin lymphoma in the era of CAR-T-cell therapy

“…The overall CRS incidence was higher after axi-cel than after tisa-cell (86.1 vs. 75.6%), but the severe CRS incidence was similar (9.1 vs. 5.3%); in addition, the overall and severe ICANS incidences were higher after axi-cel than after tisa-cel (48.8 vs. 22 and 13.9 vs. 2.9%, respectively), as was the rate of cytopenia. The ORR and CR rate were significantly higher for the axi-cel group than for the tisa-cel group (80.4 vs. 66 and (33). These data confirmed the initial results from the matching adjusted indirect comparison (MAIC) trial (37).…”

“…The patient characteristics were well balanced, and while the ORR, duration of response (DOR), PFS and OS were not significantly different between the treatments, the incidence of ICANS was higher while the CRS rate was similar after axi-cel ( 32 ). Different findings were reported in the second study ( 33 ), in which a large number of patients included in the DESCART national registry were analyzed (209 who received tisa-cell vs. 209 who received axi-cel) using propensity score matching to reduce differences in variables associated with outcomes. The overall CRS incidence was higher after axi-cel than after tisa-cell (86.1 vs. 75.6%), but the severe CRS incidence was similar (9.1 vs. 5.3%); in addition, the overall and severe ICANS incidences were higher after axi-cel than after tisa-cel (48.8 vs. 22 and 13.9 vs. 2.9%, respectively), as was the rate of cytopenia.…”

“…The ORR and CR rate were significantly higher for the axi-cel group than for the tisa-cel group (80.4 vs. 66 and 60.3 vs. 42.1%, respectively), and the 1-year PFS and OS were longer for the axi-cel group than for the tisa-cel group (46.6 vs. 33.2 and 63.5 vs. 48.8%, respectively). Survival was confirmed to be better in the axi-cel subgroups with either age ≥70 years or bulky disease ( 33 ). These data confirmed the initial results from the matching adjusted indirect comparison (MAIC) trial ( 37 ).…”

T-cell engineering strategies for tumors with low antigen density, and T-cell survival in the immunosuppressive tumor microenvironment of relapsed/refractory diffuse large B-cell lymphoma

“…Approximately 57% of patients with r/r DLBCL experience disease progression or relapse after autologous 19CAR-T cell therapy [31,32]. For example, early disease progression within 30 days or after 30 days has been reported to have a median OS of 3.75 months and 9.28 months, respectively [33].…”

Significant Progress in CAR T-Cell Therapy for Difficult-to-Treat Hematologic Malignancies

“…A comparison of axi-cel versus tisa-cel in R/R DLBCL patients was recently reported using real-life data from the French registry for commercial CAR T-cell therapy (DESCAR-T). 18 Stringent 1:1 propensity scores (PS)-matching (n=418) demonstrated that patients receiving axi-cel versus tisa-cel had higher response rates (ORR: 80.4% vs 66.0%, CR rate: 60.3% vs 42.1%; p<0.001) at a 1-year median follow-up. Furthermore, axi-cel compared with tisa-cel significantly extended PFS (median, 8.2 months vs 3.1 months, HR: 0.61 [95% CI: 0.46-0.79]; 0.0003) and OS (median, not reached vs 11.2 months; HR: 0.63 [95% CI: 0.45-0.88]; p=0.0072) (Figure 1).…”