KEY TAKEAWAYS
- Tisagenlecleucel, CD20 x CD3 bispecific T-cell-engaging monoclonal antibody, have demonstrated clinical benefits in patients with r/r FL after ≥2 lines of prior systemic therapies.
- This study evaluated the efficacy and safety outcomes of tisagenlecleucel and mosunetuzumab using MAIC with IPD from the ELARA and GO29781 trials.
- After adjusting for differences in baseline characteristics, tisagenlecleucel showed a statistically significant 11% higher ORR and a 49% relative risk reduction in PFS events compared to mosunetuzumab.
- Although not statistically significant, tisagenlecleucel showed a numerically better CR and OS based on immature survival data in both trials.
- The safety outcomes of both therapies were comparable, with similar rates of CRS and ICANS and comparable use of tocilizumab and corticosteroids for CRS management. Future analyses using IPD from both trials and real-world data are warranted.
Patients with r/r FL after 2 lines of prior systemic therapies have benefited clinically from treatment with chimeric antigen receptor T-cell therapy (tisagenlecleucel) and CD20 x CD3 bispecific T-cell-engaging monoclonal antibody (mAb) (mosunetuzumab). Using a matching-adjusted indirect comparison, we assessed the efficacy and safety of tisagenlecleucel and mosunetuzumab (MAIC).
Tisagenlecleucel IPD from ELARA (NCT03568461; 03/2022 data cut; N=98 enrolled set; N=97 safety set; median follow-up from infusion to data cut = 28.6 months [range, 22.2-37.7]) were weighted to match the aggregated baseline data of mosunetuzumab-treated pts in the GO29781 trial (NCT02500407; 08/2021 data cut; Age, sex, race, Eastern Cooperative Oncology Group performance status, Ann Arbor disease stage at enrollment, Follicular Lymphoma International Prognostic Index score, bulky disease (at least 1 lesion >6 cm), number of prior lines of therapy, refractory status to the most recent therapy, double-refractory status, progression of disease within 24 months from first anti-CD20 mAb-containing therapy, and prior autologous stem cell were all baseline characteristics that were adjusted in MAI A comparison was made between tisagenlecleucel and mosunetuzumab in terms of overall response rate (ORR), complete response rate (CR), progression-free survival (PFS), and overall survival (OS).
Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were among the adverse events studied, as were the administrations of tocilizumab and corticosteroids for the treatment of CRS. ORR and PFS were better for tisagenlecleucel than for mosunetuzumab after adjusting for differences in baseline characteristics. The overall response rate for tisagenlecleucel was 11% higher than that of paclitaxel (91% vs. 80%, P0.05), and the increase in CR was 13% higher than that of paclitaxel (60% vs. 73%, P=0.10) (Figure 1A).
Post-matching, tisagenlecleucel had a lower hazard ratio for progression-free survival (PFS) than the control group did (HR [95% CI] 0.51 [0.29, 0.87]; P<0.05). When comparing tisagenlecleucel and mosunetuzumab, the former had a lower hazard of death (HR [95% CI] 0.52 [0.17, 1.58]; P=0.25), but this difference was not statistically significant due to limited information regarding long-term outcomes (OS). Grade 3 events were uncommon; CRS was treated similarly with tocilizumab and corticosteroids after adjustment for confounding variables. Tisagenlecleucel was associated with a statistically significant 11% higher ORR and a 49% relative risk reduction in PFS events compared to mosunetuzumab in patients with r/r FL and numerically better but not significant CR and OS (based on immature survival data), and similar safety outcomes. More research incorporating IPD from clinical trials and real-world data is necessary.
Source: https://tandem.confex.com/tandem/2023/meetingapp.cgi/Paper/21265
Clinical trial: https://clinicaltrials.gov/ct2/show/NCT02500407/
Fowler, N.H., Schuster, S.J., Yang, H., Xiang, C., Ramos, R., Maier, H., Anjos, C., Jousseaume, E., Thieblemont, C. and Dreyling, M. (2023). Matching-Adjusted Indirect Comparison of Efficacy and Safety for Tisagenlecleucel and Mosunetuzumab in Patients (pts) with Relapsed/Refractory Follicular Lymphoma (r/r FL). [online] tandem.confex.com. Available at: https://tandem.confex.com/tandem/2023/meetingapp.cgi/Paper/21265 [Accessed 23 Feb. 2023].
