![]() ![]() These had more delayed bone marrow uMRD, and early detectable MRD of ≥10 -5, despite longer treatment courses owing to the trial's MRD-driven treatment duration. ![]() In contrast, 40% of patients did not achieve ΔMRD400. In the study, 60% of patients exhibited rapid MRD response kinetics (ΔMRD400 achievers) and these patients had rapid bone marrow uMRD (100% within 8 months) and more durable uMRD of <10 -5. "Importantly, the MRD kinetics data we presented at ASH suggest that it's not just whether or not you achieve uMRD, but rather your early MRD response kinetics might predict MRD outcomes and define biologic differences," Soumerai told MedPage Today. The combination achieved frequent, durable uMRD responses, with 89% of patients achieving uMRD in both the peripheral blood and the bone marrow therapy was discontinued after a median of 10 months. ![]() The speed with which uMRD is achieved may be an important factor, according to Jacob Soumerai, MD, of Massachusetts General Hospital Cancer Center in Boston, and Andrew Zelenetz, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York City.Īt last year's American Society of Hematology (ASH) virtual annual meeting, their group presented a study looking at MRD-driven time-limited therapy with zanubrutinib (Brukinsa), obinutuzumab, and venetoclax in previously untreated CLL. It's pretty clear that patients with undetectable MRD do better, and I think MRD measurement will be the way of the future." That's still up for debate, and the big question is whether MRD results are actionable. "Studies in venetoclax-based treatment have found achieving negative MRD levels to be prognostic of favorable outcomes with pronounced better PFS and OS."Īs to whether MRD levels are ready to guide clinical decision-making, Coombs was cautious: "MRD measurement is not necessarily standard of care at the moment, but it will continue to emerge as an important goal of treatment in fixed-duration CLL regimens," said Catherine Coombs, MD, of the University of North Carolina School of Medicine in Chapel Hill. MRD in this study was detected at a sensitivity level of 10 -6. Significantly, regular MRD assessments over time demonstrated deep clearance of CLL cells in the peripheral blood of venetoclax-obinutuzumab recipients, testifying to its potential as an end-of-treatment prognostic parameter. Estimated 4-year PFS and OS were also higher in the venetoclax arm. Recently updated results of the CLL14 trial showed that treatment-naive patients given fixed-duration venetoclax (Venclexta) and obinutuzumab (Gazyva) exhibited detectable MRD at a later timepoint than those given chlorambucil plus obinutuzumab, with only 7.9% in the venetoclax arm requiring a next line of therapy more than 3 years after treatment cessation. Given the utility in evaluating depth of response, determining uMRD status is becoming a focus of outcomes in CLL trials, particularly of fixed-duration therapy. MRD has correlated with favorable progression-free survival (PFS) and overall survival (OS) after chemoimmunotherapy. ![]()
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