Session: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Lymphoid Leukemias, CLL, Diseases, therapy sequence, Therapies, Lymphoid Malignancies, Minimal Residual Disease
Methods: Overall, 389 pts were randomized to VenR (2 years of Ven, with R for the first 6 months) or 6 months of BR. Pts in either arm with PD were followed for disease response to any subsequent anti-CLL therapeutic regimens, PFS and OS. A sub-study, introduced in 2018, allowed pts who developed PD following treatment with VenR or BR to receive the MURANO VenR regimen. Pts who initiated new anti-CLL therapy without a response assessment reported by the investigator, were considered unevaluable.
Results: At the final clinical cutoff date of August 3, 2022, all pts had ceased study-specified treatment and the median follow-up of the main study was 85.7 (range: 0–99.2) months. PFS and OS benefits were maintained at the 7-year follow-up (Kater et al. EHA 2023).
Overall, 73/194 (37.6%) pts in the VenR arm had not received a next-line therapy at the final cutoff, and 26 pts had died without subsequent therapy. Median TTNT or death with VenR was 63.0 months vs 24.0 months with BR (hazard ratio: 0.30). Following PD, 95/194 (49.0%) pts randomized to VenR and 131/195 (67.2%) pts randomized to BR had received subsequent anti-CLL therapy; the median (range) time off therapy in these pts was 28.3 months (-0.1–68.6) and 17.9 months (0.7–82.4), respectively. Of the 95 VenR pts receiving subsequent anti-CLL therapy, 30 (32.3%) received BTKi therapy (ibrutinib [n=25], acalabrutinib [n=4] and zanubrutinib [n=1]), with 18 ongoing at the time of the final cutoff; 47 (51.6%) received Ven-based therapy, with 12 ongoing at the time of the final cutoff; and 16 (17.2%) received chemoimmunotherapy (CIT). Two pts received a non-CLL therapy for another malignancy so were excluded from the subsequent analysis. Of the 131 BR pts receiving subsequent therapy, 79 (60.3%) received BTKi therapy (ibrutinib [n=69], acalabrutinib [n=6] and zanubrutinib [n=4]), with 20 ongoing at the time of the final cutoff; 17 (13.0%) received Ven-based therapy, with 3 ongoing at the time of the final cutoff; 24 (18.3%) received CIT; and 11 (8.4%) received other novel agents. Median time from randomization to second PFS event was 85.9 months (95% confidence interval [CI]: 81.8–88.2) in pts randomized to VenR and 48.4 months (95% CI: 44.5–56.6) in pts randomized to BR; p<0.0001 (Figure).
Best overall response (BOR; defined as complete remission [CR], CR with incomplete count recovery, partial remission [PR] and nodular PR) rates to first subsequent anti-CLL therapy for pts with evaluable responses were 75/93 (80.6%) for VenR and 85/107 (79.4%) for BR. Among evaluable pts previously treated with VenR and BR, the BOR rate to subsequent BTKi therapy was 19/22 (86.4%) and 51/65 (78.5%), respectively, while BOR rate to subsequent Ven-based therapies was 32/42 (76.2%) and 15/17 (88.2%), respectively.
Conclusions: Final data from MURANO demonstrate that, despite the majority of BR pts receiving novel therapies after relapse on MURANO, there was a significantly prolonged time to second PFS event observed in favor of the VenR arm. Pts who had relapsed and received retreatment or crossed over to Ven-based regimens or subsequent BTKi therapy also demonstrated high response rates. These results indicate that early intervention with fixed-duration VenR in R/R CLL is an effective approach and does not compromise subsequent therapy response.
Disclosures: Harrup: FibroGen: Research Funding; F. Hoffmann-La Roche Ltd, Beigene: Research Funding; F. Hoffmann-La Roche Ltd, Takeda: Current equity holder in publicly-traded company. Kater: Astra Zeneca: Consultancy, Honoraria, Research Funding; LAVA: Consultancy, Honoraria, Research Funding; Genentech, Inc.: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding. Eichhorst: BeiGene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Gilead: Consultancy, Research Funding; Janssen: Consultancy, Research Funding, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; MSD: Consultancy, Honoraria, Speakers Bureau; F. Hoffmann-La Roche Ltd: Honoraria, Research Funding, Speakers Bureau; Lilly: Consultancy, Speakers Bureau; Abbvie: Consultancy, Honoraria, Research Funding, Speakers Bureau. Owen: F. Hoffmann-La Roche Ltd, AbbVie, Astrazeneca, Beigene, Merck, Incyte, Seattle Genetics, Novartis: Honoraria. Chyla: Abbvie: Current holder of stock options in a privately-held company; Abbvie: Current Employment. Jin: Genentech, Inc./F. Hoffmann-La Roche Ltd: Ended employment in the past 24 months; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company; Genentech, Inc./F. Hoffmann-La Roche Ltd: Current Employment. Jiang: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. Chang: F. Hoffmann-La Roche Ltd: Current Employment. Millen: Roche Products Ltd: Current Employment; KWF Proposal, Netherlands: Research Funding; Hubrecht Institute, Utrecht, The Netherlands: Ended employment in the past 24 months. Lefebure: F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company; F. Hoffmann-La Roche Ltd: Current Employment. Thadani-Mulero: F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company; Roche Products Ltd: Current Employment. Boyer: F. Hoffmann-La Roche Ltd: Current Employment. Seymour: AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Beigene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics: Consultancy; Genor Bio: Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Hoffmann-La Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; F. Hoffmann-La Roche Ltd: Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees.
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