SESSION 4: CHRONIC LYMPHOCYTIC LEUKEMIA
ADAPTATION OF CHRONIC LYMPHOCYTIC LEUKEMIA TO IBRUTINIB IS MEDIATED BY EPIGENETIC PLASTICITY OF RESIDUAL DISEASE AND BY-PASS SIGNALING VIA MAPK PATHWAY abstract
L Terzi di Bergamo, G Forestieri, J. W Loh, A Singh, et al.
The study authors conclude that MRD under ibrutinib adapts its phenotype, mainly in an epigenetic way to maintain functional competence of BCR signaling through the MAPK pathway.
GENETIC MARKERS AND OUTCOME WITH FRONT LINE OBINUTUZUMAB PLUS EITHER CHLORAMBUCIL OR VENETOCLAX - UPDATED ANALYSIS OF THE CLL14 TRIAL abstract
E Tausch, C Schneider, D Yosifov, S Robrecht, et al.
The study authors conclude that IGHV mutation status and del(17p) proved to be prognostic with obinutuzumab+venetoclax (VenG) andobinutuzumab+chlorambucil (GClb), while none of the other prognostic factors besides TP53 affected outcome with VenG. After VenG no BCL2 resistance mutations were identified at relapse supporting re-treatment concepts.
VENETOCLAX-OBINUTUZUMAB MODULATES CLONAL GROWTH: RESULTS OF A POPULATION-BASED MINIMAL RESIDUAL DISEASE MODEL FROM THE RANDOMIZED CLL14 STUDY abstract
O Al-Sawaf, C Zhang, T Lu, M. Z Liao, et al.
The study authors conclude that their analysis establishes a robust, population-based model of MRD growth dynamics that allows the description of growth trajectories and treatment effects after treatment cessation. In addition to more effective MRD eradication with venetoclax and the CD20 antibody obinutuzumab, their results demonstrate that MRD growth is modulated more efficiently by BCL2-targeting treatment in contrast to genotoxic chemoimmunotherapy.
CAPTIVATE PRIMARY ANALYSIS OF FIRST-LINE TREATMENT WITH FIXED-DURATION IBRUTINIB PLUS VENETOCLAX FOR CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)/SMALL LYMPHOCYTIC LYMPHOMA (SLL) abstract
C. S. L Tam, J. N Allan, T Siddiqi, T. J Kipps, et al.
The study authors conclude that 1st-lineibrutinib (I) + venetoclax (V) is an all-oral, once-daily, chemotherapy-free, fixed-duration regimen that provides deep, durable responses in patients with CLL/SLL, including those with high-risk genomic features. CR, uMRD rates, PFS, and OS appear favorable. No new safety signals were identified; the safety profile of I+V was consistent with known AEs for each agent.
FIRST RESULTS OF A HEAD-TO-HEAD TRIAL OF ACALABRUTINIB VERSUS IBRUTINIB IN PREVIOUSLY TREATED CHRONIC LYMPHOCYTIC LEUKEMIA abstract
P. Hillmen, J. C. Byrd, P. Ghia, A. P. Kater, et al.
The study authors conclude that In this first head-to-head trial of BTKis in CLL, acalabrutinib demonstrated non-inferior PFS with less cardiotoxicity and fewer discontinuations due to AEs vs ibrutinib.
BENDAMUSTINE, FOLLOWED BY OBINUTUZUMAB, ACALABRUTINIB AND VENETOCLAX IN PATIENTS (PTS) WITH RELAPSED/REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA (CLL): CLL2-BAAG TRIAL OF THE GCLLSG abstract
P Cramer, M Fürstenau, S Robrecht, A Giza, et al.
The study authors conclude that sequential treatment with bendamustine (B) debulking, followed by the triplet combination of obinutuzumab (G), acalabrutinib (A) and venetoclax (V) was well tolerated. Although the primary endpoint was not met with the given sample size, the ORR of 100% and a rate of uMRD of 76% in PB at the end of the induction phase compare favorably to other regimens for r/r CLL. The lower uMRD rate may be explained by the redistribution phenomenon caused by BTK-I and could improve with continued maintenance treatment in the long run.