KEY TAKEAWAYS
- Based on ZUMA-3 pivotal Phase 2 results, brexucabtagene autoleucel (KTE-X19) has been approved in the US for adults with R/R B-ALL.
- In the Phase 2 portion, the overall CR rate (CR + CRi) was 71% in patients who received a single infusion of KTE-X19.
- In patients with 1 vs.≥2 prior lines of therapy, CR/CRi rates were 90% vs. 67%, respectively.
- Patients with prior blinatumomab at baseline had a lower CR/CRi rate and shorter DOR than those without prior blinatumomab.
- Survival appeared better in patients without prior exposure to blinatumomab or prior alloSCT, but limited patient numbers in some subgroups.
Based on the results of the ZUMA-3 study, brexucabtagene autoleucel (KTE-X19) has been approved for use in adults with R/R B-ALL. There was a 71% complete remission (CR) rate in the pivotal Phase 2 portion (CR + CR with incomplete hematologic recovery [CRi]; N=55; median follow-up 16.4 months; Shah et al. Lancet 2021). Here, we detail the results of ZUMA-3 according to pre- and post-transplantation treatments (sub-alloSCT).
Patients with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) received a single infusion of KTE-X19 after leukapheresis and conditioning chemotherapy. All patients treated at the optimal dose (1106 CAR T cells/kg) have outcomes that have been independently reviewed and reported.
The Phase 2 patients who were followed up as of July 23 had been doing so for a median of 26.8 months (range, 20.7-32.6). Around 10 patients (18%) had received one prior line of therapy before baseline, while 45 patients (82%) had received two or more. Patients who had only received one prior line of therapy had a CR/CRi rate of 90% (55-100), while those who had received two or more prior lines of therapy had a CR/CRi rate of 67% (51-80), a DOR of 4.7 months (1.8-not estimable [NE]), and an OS of not reached (NR) (2.1-NE) vs. 25.4 months (14.2-NE). Patients with 1 vs. 2 prior lines of therapy were more likely to experience a cytokine release syndrome (CRS) of grade (Gr) ≥3, and those with 1 vs. 2 prior lines of therapy were more likely to experience a neurologic event of grade (Gr)≥3.
The CR/CRi rate (95% CI) was 60% (39-79) in the 25 patients (45%) who had prior blinatumomab at baseline, and it was 80% (61-92) in the 30 patients (55%) who did not. DOR was 19.1 months (95% CI: 1.3-NE), and OS was 14.2 months (95% CI: 3.2-26.0) in patients who had received prior blinatumomab compared to patients who had not (18.6-NE). The rates of Grade 3 CRS and Grade 3 neurologic events were 24% and 23% in patients with and without prior blinatumomab, respectively.
The CR/CRi rates were 70% (47-87) in the group that had previously undergone alloSCT and 72% (53-86) in the group that had not. There were 23 such patients (42%). Medians (95% CI) for DOR were 14.6 months (8.7-23.6) and NR (4.7-NE) in patients who had undergone a prior alloSCT versus those who had not undergone such a procedure (9.0-NE). In addition, patients who had undergone alloSCT in the past were significantly less likely to experience grade 3 CRS (17% vs 28%) and grade 3 neurologic events (26% vs 25%).
Median (95% CI) DOR was not reached (NE-NE) vs. 14.6 months (8.7-23.6) for patients who achieved CR/CRi and did (n=10) vs. did not (n=29) proceed to sub-alloSCT following KTE-X19 infusion, and median (95% CI) OS was not reached (NE-NE) vs. 26.0 months (NE-NE) for patients who did not (18.6-NE). The subgroup outcomes in Phase 2 patients were supported by a pooled analysis of all Phase 1 and 2 patients treated at the pivotal dose (N=78) (median follow-up, 29.7 months [range, 20.7 to 58.3]). KTE-X19 was effective and had tolerable side effects for adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL), but survival appeared better in patients without these prior therapies and in earlier lines of therapy, despite small patient numbers in some subgroups.
Source: https://tandem.confex.com/tandem/2023/meetingapp.cgi/Paper/21034
Clinical trial: https://clinicaltrials.gov/ct2/show/NCT02614066/
Shah, B.D., Cassaday, R.D., Park, J.H., Houot, R., Oluwole, O.O., Logan, A.C., Boissel, N., Leguay, T., Bishop, M.R., Topp, M.S., Tzachanis, D., OâDwyer, K.M., Arellano, M.L., Lin, Y., Baer, M.R., Schiller, G.J., Subklewe, M., Abedi, M., Minnema, M.C. and Wierda, W.G. (2023). Subgroup Analyses of Kte-X19, an Anti-CD19 Chimeric Antigen Receptor (CAR) T-Cell Therapy, in Adult Patients (Pts) with Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia (R/R B-ALL) in Zuma-3. [online] tandem.confex.com. Available at: https://tandem.confex.com/tandem/2023/meetingapp.cgi/Paper/21034 [Accessed 23 Feb. 2023].
