642. CLL: Therapy, excluding Transplantation I
William G. Wierda, Constantine S. Tam, John N. Allan, et al.
Authors Conclusion from the Abstract: First-line Ibr + Ven treatment is an all-oral, once-daily, chemotherapy-free regimen that confers high rates of PB and BM uMRD in pts with CLL, and a 90% reduction in high-risk TLS monitoring (Siddiqi, EHA 2020). The 1-year DFS in pts randomized to placebo after Ibr + Ven combination was similar to that of pts continuing Ibr, supporting a fixed-duration treatment that offers treatment-free remissions in pts with CLL/SLL. The depth of response achieved with this regimen is reflected in the 30-mo PFS rate of ~95% across all treated pts. The safety profile of Ibr + Ven was consistent with known AEs for Ibr and Ven, and no new safety signals emerged.
Talha Munir, Rebecca H. Boucher, Nichola Webster, et al.
Authors Conclusion from the Abstract: After 38 months, the response to IBR+VEN is sustained despite planned discontinuation of therapy in MRD negative patients. The initial rate of disease depletion (during the first two months of combined IBR+VEN exposure) is highly predictive of longer-term response to combination IBR+VEN treatment in relapsed/refractory CLL. Patients who do not show rapid disease clearance and have persistent MRD after 12 months of combination IBR+VEN usually have stable or slowly decreasing disease levels akin to that seen in IBR monotherapy. These data will be updated at ASH 2020.
Arnon P. Kater, Thomas J. Kipps, Barbara Eichhorst, et al.
Authors Conclusion from the Abstract: Five-yr data from MURANO demonstrate sustained PFS and OS benefit with VenR vs BR. In the VenR cohort, uMRD at EOT is associated with improved OS. Unmutated IGVH, del(17p) and GC (≥3 CNV) are associated with higher rates of MRD conversion and subsequent PD after attaining uMRD at EOT. Overall, a substantial proportion of pts who completed Ven Tx retained uMRD 36 mo after treatment cessation, displaying durable response following 2-yr fixed-duration VenR.
Anthony R. Mato, Stephen J. Schuster, Francine M. Foss, et al.
Authors Conclusion from the Abstract: This clinical trial met its primary endpoint. The once-daily oral triple combination therapy DTRM-555 has an acceptable safety profile. Encouraging clinical activity was observed in several high-risk, multi-refractory pts with RT (median 5 prior therapies, ORR 45%) or r/r DLBCL (median 2 prior therapies, ORR 60%), including pts previously treated with targeted therapies, cellular therapies, checkpoint inhibitors and other experimental agents. A phase II US expansion study is underway targeting pts with RT, r/r DLBCL, r/r transformed follicular lymphoma and BTKi/BCL2 inhibitor exposed r/r CLL pts.
Othman Al-Sawaf, Can Zhang, Sandra Robrecht, et al.
Authors Conclusion from the Abstract: This analysis demonstrates that individual clonal growth rates can be used to estimate the MRD doubling time after a fixed-duration treatment. Clonal growth was lower after Ven-Obi than after Clb-Obi, indicating more effective MRD eradication and clonal growth modulation with Ven-Obi. In a considerable subgroup of Ven-Obi treated patients, no clonal growth was measurable during observation, indicating deepest remissions.
Shuhua Yi, Jun Du, Ying Yu, et al.
Authors Conclusion from the Abstract: The efficacy of this TPM regimen is higher than the history reports with limited adverse events. The multiple-center clinical trial has been initiated to validate this conclusion.