EFS (Embryonal Fyn-Associated Substrate)

Early use of anti-PD-(L)1 therapy is associated with prolonged disease control and may be linked to enhanced responsiveness to subsequent therapies, mostly based on NSCLC data. Additionally, EFS2/PRFS2/PFS2 are solid candidate surrogates for OS and could be considered for routine inclusion and prespecified into immunotherapy RCTs to better capture long-term benefit and inform regulatory, clinical, and reimbursement decision-making.

P=N/A, N=70, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Not yet recruiting --> Recruiting

P=N/A, N=70, Not yet recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Among the 271 patients who started a 2L treatment, 203 (75%) received a BTKi at 2L – 101 (50%) ibrutinib, 76 (37%) acalabrutinib, and 26 (13%) zanubrutinib. In this multicenter retrospective study, initiation of 1L BR (with or without rituximab maintenance) resulted in a 7-year OS of 57%. Median EFS2 for sequential 1L BR and 2L BTKi was 72.1 months. In context, the SHINE study reported a median PFS of 80.6 months in the BR (with rituximab maintenance) plus ibrutinib arm and a 7-year OS of 57% in the ibrutinib arm and 55% in the placebo arm, where 39% of patients received a BTKi in 2L.

P3, N=421, Not yet recruiting, Alliance for Clinical Trials in Oncology

P=N/A, N=2000, Completed, Takeda | Active, not recruiting --> Completed

Second line treatments included BTK inhibitors (BTKi) in 61 pts (50%), bendamustine based therapy in 14 pts (12%), lenalidomide and/or bortezomib based therapy in 14 pts (12%), venetoclax in 3 pts (3%), and other classes of treatment in 30 pts (25%). We observed a median EFS2 of 26 mo and median EFS3 of 19 mo in a contemporary prospective cohort of pts with RR MCL. We did not observe an association between class of treatment received and EFS2 or EFS3, but observed inferior EFS2 and EFS3 for patients with POD24 following frontline therapy compared with patients with later first relapse highlighting the higher risk nature of this population. The observed OS2 and OS3 outcomes in this prospective cohort exceed historical estimates for relapsed MCL prior to availability of newer therapies, provide context for interpreting single arm trial results, and may inform future clinical trial design.