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Minimal Residual Disease and Chemotherapy-Free Regimens in CLL: Surrogate Prognostic Marker?

By: Cordi Craig
Posted: Friday, February 28, 2020

Minimal residual disease is a standard marker for patient outcomes after chemoimmunotherapy, although its prognostic value after chemotherapy-free regimens is less established. Kirsten Fischer, MD, of the University Hospital, Cologne, Germany, and colleagues found that patients with chronic lymphocytic leukemia (CLL) treated with fixed-duration venetoclax and obinutuzumab achieved high and sustainable rates of undetectable minimal residual disease. The findings, presented at the 2019 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 36) and published in the journal Blood, support its role as a marker for outcomes with chemotherapy-free treatment regimens.

The study included 432 previously untreated patients with CLL. Patients received chlorambucil (n = 216) or venetoclax (n = 216) in combination with obinutuzumab. The investigators took peripheral blood samples from all patients for minimal residual disease. Bone marrow samples from those patients with a treatment response were assessed.

Patients treated with venetoclax and obinutuzumab achieved higher rates of undetectable minimal residual disease in peripheral blood samples and bone marrow samples at the end of treatment than those who received chlorambucil plus obinutuzumab. Detectable minimal residual disease in peripheral blood was found in 19 patients treated with venetoclax versus 103 patients treated with chlorambucil.

Of the patients treated with venetoclax who had undetectable minimal residual disease in peripheral blood samples, 55.8% achieved complete responses versus 40.8% of those treated with chlorambucil. The majority of patients treated with venetoclax and obinutuzumab who achieved undetectable minimal residual disease measurements in peripheral blood samples also achieved comparable bone marrow clearance (74.8%). The depth of response (as measured by next-generation sequencing) was also reported to be “more profound” among those treated with venetoclax than chlorambucil.

“Further landmark analysis of progression-free survival by minimal residual disease status showed that undetectable minimal residual disease translated into improved progression-free survival regardless of the clinical response status at the end of treatment,” the researchers concluded.

Disclosure: For full disclosures of the study authors, visit ashpublications.org.



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