TRIAL in PROGRESS: PROSPECTIVE STUDY of FIXED-DURATION IBRUTINIB+VENETOCLAX (IBR+VEN) for FIRST-LINE TREATMENT of PATIENTS with CHRONIC LYMPHOCYTIC LEUKEMIA in A REAL-WORLD SETTING: The REALITY STUDY.

Munir, T.; De Farias, D.L.C.; Messahel, B.; Srikanthan, S.; Xu, P.; Morsy, M.; Kavanagh, C.; Tapprich, C.; Ghia, P.

TRIAL in PROGRESS: PROSPECTIVE STUDY of FIXED-DURATION IBRUTINIB+VENETOCLAX (IBR+VEN) for FIRST-LINE TREATMENT of PATIENTS with CHRONIC LYMPHOCYTIC LEUKEMIA in A REAL-WORLD SETTING: The REALITY STUDY.

All Authors

Munir, T.

De Farias, D.L.C.

Messahel, B.

Srikanthan, S.

Xu, P.

Morsy, M.

Kavanagh, C.

Tapprich, C.

Ghia, P.

LTHT Author

Munir, Talha

LTHT Department

Oncology
Haematology

Publication Date

2024

Item Type

Conference Abstract

Subject

ADULT , LEUKAEMIA , TREATMENT OUTCOME , CLINICAL PROTOCOLS , COHORT STUDIES , COMORBIDITY , DIAGNOSIS , DRUG THERAPY , WOMEN , FOLLOW-UP-STUDIES , HOSPITALISATION , NEOPLASM, RESIDUAL , MULTICENTRE STUDIES AS TOPIC , SURVIVAL RATE , CLINICAL TRIALS AS TOPIC , DISEASE-FREE SURVIVAL , PROSPECTIVE STUDIES , SURVEYS AND QUESTIONNAIRES , ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS , ANTINEOPLASTIC AGENTS , ANTIBODIES, MONOCLONAL

Abstract

Background: In the phase 3 GLOW study with up to 5y follow-up, fixed-duration (FD) Ibr+Ven showed superior progression-free survival (PFS; 54-mo rate: 66.5% vs 19.5%) and overall survival (OS; 54-mo rate: 84.5% vs 63.7%) vs chlorambucil+obinutuzumab (Clb+O) in patients (pts) with previously untreated chronic lymphocytic leukemia (CLL) who were older or had comorbidities (Moreno et al. ASH 2023). Ibr+Ven also prolonged time to next treatment (TTNT) and reduced the risk of requiring second-line therapy by 82% vs Clb+O (HR 0.185 [95% CI, 0.096-0.355]; p<0.0001). In the phase 2 CAPTIVATE study, first-line (1L) Ibr+Ven demonstrated deep and durable responses in pts with CLL, including those with high-risk features (Tam et al. Blood 2022). These findings led to regulatory approval of the all-oral, FD combination of Ibr+Ven for 1L treatment (tx) in CLL in many countries/regions, including Europe, UK, and Canada. While clinical benefit of 1L Ibr+Ven has been established in CLL in clinical studies, real-world (RW) evidence is limited. The REALITY study will prospectively investigate clinical and safety outcomes of Ibr+Ven in routine clinical practice. Aim(s): To gain insights on tx patterns, tx decision drivers, clinical effectiveness, and safety of 1L Ibr+Ven in pts with CLL treated in routine clinical practice. Method(s): REALITY is an international, multicenter, prospective observational cohort study in the RW clinical setting. The study will enroll pts with previously untreated CLL from hospitals and medical institutions where Ibr+Ven is routinely used in clinical practice. The decision to start Ibr+Ven tx will be made independently of and prior to pt enrollment in the study. Pts aged >=18y with a confirmed diagnosis of CLL who have been prescribed Ibr+Ven and sign the informed consent are eligible for inclusion. The dosing schedule is per label, with a 3-cycle lead-in of Ibr 420 mg/d followed by 12 cycles of Ibr+Ven, with Ven dose ramp-up from 20 to 400 mg over 5 weeks from Cycle 4 (Figure). Primary data sources are medical records and pt and physician questionnaires. Data will be collected at pt visits every 3 tx cycles (~every 12 wks). The study duration will be ~4y, with 1.5y enrollment, up to 15 cycles of Ibr+Ven during the tx phase, and up to 1y follow-up phase. Approximately 200 pts will be enrolled in Europe, Middle East, and Latin America. The primary endpoint is overall response rate (ORR) by the end of 15 tx cycles, per physician assessment based on iwCLL 2018 criteria. Secondary endpoints include: 1) factors associated with physician decision to initiate Ibr+Ven in routine clinical practice; 2) ORR by the end of 3, 6, 9, and 12 tx cycles, duration of response (DOR), PFS, OS, measurable residual disease, and tx interruptions/discontinuation and dose adjustments, time on tx, time to tx discontinuation (TTD), and TTNT; 3) pt-reported outcomes by EORTC QLQ-CLL17; 4) safety: adverse events (AEs), serious AEs, tumor lysis risk, and hospitalization rate for Ven ramp-up; and 5) medical resource utilization. ORR will be summarized with frequency (%), and 2-sided 95% CIs will be calculated using the normal approximation. Time-to-event endpoints (eg, TTD, TTNT, DOR, PFS, OS) will be analyzed using the Kaplan-Meier product limit method to estimate survival distribution and median time to event. Result(s): The study is in progress and results will be reported at a future medical congress. Summary/Conclusion: The REALITY study will provide RW data on the management of pts with CLL treated with Ibr+Ven in routine clinical practice. (Table present).