KEY TAKEAWAYS
- The ZUMA-1 Cohort 6 (N=40) trial, which evaluated the safety of prophylactic and earlier corticosteroids and/or tocilizumab, demonstrated an improved safety profile without compromising response rate or durability.
- The trial included patients with relapsed or refractory large B-cell lymphoma who received a single axi-cel infusion and corticosteroid prophylaxis.
- At 2 years of follow-up, no new cases of Grade ≥3 cytokine release syndrome were reported, and the incidence of Grade ≥3 neurologic events increased slightly from 15% to 18%.
- The overall response rate was 95%, with a durable response observed in 53% of patients at 2 years.
- The long-term safety profile of axi-cel in patients with relapsed or refractory large B-cell lymphoma continued to be improved with the toxicity management strategy used in Cohort 6.
Cohort 6 (N=40) of the ZUMA-1 safety management study, which looked at the effects of prophylactic corticosteroids and earlier corticosteroids and/or tocilizumab on safety outcomes, showed an improved safety profile (no Grade 3 cytokine release syndrome [CRS]; 15% Grade 3 neurologic events [NEs]) compared to the pivotal Cohorts 1+2, without sacrificing response rate or durability (95% ORR, 80% New findings after 2 years are shown here.
Patients with R/R LBCL who were candidates for the study underwent leukapheresis (optional bridging therapy) and conditioning chemotherapy, followed by a single infusion of axi-cel. Patients in Cohorts 3+4 who were pretreated with corticosteroids (once-daily oral dexamethasone 10 mg on Days 0 [before axi-cel], 1, and 2) and/or tocilizumab for CRS and NE had a lower incidence of these complications (Oluwole, et al. Br J Haematol. 2021). Seriousness and frequency of CRS and NEs were the key measures of success. The secondary goals were the overall response rate (as determined by the investigator), duration of response, progression-free survival, overall survival, and circulating chimeric antigen receptor T cells.
The median follow-up period for the 40 patients treated as of December 16, 2021, was 26.9 months. No additional cases of CRS have been recorded since the 1-year analysis (no patients have developed Grade 3 CRS so far). Between the 1-year and 2-year analyses, the prevalence of Grade 3 NEs rose from 15% to 18%. In addition, two patients developed new NEs: one patient developed Grade 2 dementia (beginning on Day 685 and continuing at the time of data cutoff; unrelated to axi-cel), and another patient developed Grade 5 axi-cel-related leukoencephalopathy.
Around 6 additional infections were identified in the year following the 1-year analysis: COVID-19 grades 1, 2, and 5 (n=1 each), Pneumocystis jirovecii pneumonia (n=1), an unexplained infectious episode with an inflammatory syndrome (n=1), and herpes zoster (n=2). Since the 1-year analysis, 8 deaths have occurred (2 from COVID-19, 2 from progressive illness, and 2 from leukoencephalopathy.
Similar to the 1-year analysis, the ORR was 95% (80% CR). In the meantime, the median DOR and PFS have been attained (25.9 months [95% CI, 7.8-not estimable] and 26.8 months [95% CI, 8.7-not estimable], respectively). We have yet to reach the median age of occurrence. According to Kaplan-Meier estimates, DOR, PFS, and OS rates over 2 years were 53%, 53%, and 62%, respectively. For the 18 points (45%) in continuing response as of the data cutoff, CR was the optimal response for every single one. As of Month 24, 14/20 patients with evaluable samples (70%), compared to 23/36 patients (64%), exhibited detectable CAR T cells.
ZUMA-1 Cohort 6 toxicity management method has shown to improve the long-term safety profile of axi-cel in patients with R/R LBCL, and with 2 years of follow-up, this improvement has persisted. Nevertheless, responses were still high, lasting, and comparable to those in Cohorts 1+2. (Locke, et al. Lancet Oncol. 2019).
Source: https://tandem.confex.com/tandem/2023/meetingapp.cgi/Paper/20913
Clinical trial: https://clinicaltrials.gov/ct2/show/NCT02348216/
Oluwole, O.O., Forcade, E., Muñoz, J., Guibert, S. de, Vose, J.M., Bartlett, N.L., Lin, Y., Deol, A., McSweeney, P.A., Goy, A.H., Kersten, M.J., Jacobson, C.A., Farooq, U., Minnema, M.C., Thieblemont, C., Timmerman, J.M., Stiff, P.J., Avivi, I., Tzachanis, D. and Zheng, Y. (2023). Prophylactic Corticosteroid Use with Axicabtagene Ciloleucel (Axi-Cel) in Patients (Pts) with Relapsed/Refractory Large B-Cell Lymphoma (R/R LBCL): 2-Year Follow-up of Zuma-1 Cohort 6. [online] tandem.confex.com. Available at: https://tandem.confex.com/tandem/2023/meetingapp.cgi/Paper/20913 [Accessed 23 Feb. 2023].
