Assessment of minimal residual disease was associated with improved prediction of outcome in responders, as well as complete responders, in patients with chronic lymphocytic leukemia (CLL) who respond to treatment. Kovacs et al reported these findings, which are based on an analysis of two phase III studies of the German CLL Study Group, in the Journal of Clinical Oncology. Barbara Eichhorst, MD, of the Center of Integrative Oncology Cologne-Bonn, University of Cologne, is the corresponding author of this article.
In the study, progression-free survival and overall survival among 554 patients in the 2 trials (CLL8 = fludarabine and cyclophosphamide [FC] vs FC plus rituximab (Rituxan); CLL10 = FC plus rituximab vs bendamustine plus rituximab) were analyzed according to minimal residual disease assessed in peripheral blood at a threshold of 10-4 and clinical response.
Outcome by Minimal Residual Disease and Response
Median progression-free survival from a landmark at the end of treatment was 61 months for those with minimal residual disease–negative complete remission, 54 months for minimal residual disease–negative partial response, 35 months for minimal residual disease–positive complete remission, and 21 months for minimal residual disease–positive partial response. Progression-free survival did not differ significantly between minimal residual disease–negative complete remission or partial response (hazard ratio [HR] = 1.24, P = .228). It was longer in those with minimal residual disease–negative complete remission vs minimal residual disease–positive complete remission (HR = 1.99, P = .004) and vs minimal residual disease–positive partial response (HR = 4.27, P < .001) and for patients with minimal residual disease–negative partial response vs minimal residual disease–positive complete remission (HR = 0.63, P = .048). Among minimal residual disease–positive patients, progression-free survival was improved for complete remission vs partial response (HR = 2.00, P = .002).
Compared with minimal residual disease–negative complete remission, only patients with minimal residual disease–positive partial response had significantly shorter median overall survival (not reached vs 72 months, P = .001), with no significant difference being found vs minimal residual disease–negative partial response (P = .612) or minimal residual disease–positive complete remission (P = .853).
Patients with minimal residual disease–negative partial response with residual splenomegaly had similar progression-free survival vs those with minimal residual disease–negative complete remission (63 vs 61 months, P = .354). Patients with minimal residual disease–negative partial response with lymphadenopathy had shorter progression-free survival (31 months, P < .001).
The investigators concluded: “[Minimal residual disease] quantification allows for improved [progression-free survival] prediction in both patients who achieve [partial response] and [complete remission], which thus supports its application in all responders. In contrast to residual lymphadenopathy, persisting splenomegaly does not impact outcome in patients with “[minimal residual disease]-negative [partial response].”
The study was supported by the German Jose Carreras Leukemia Foundation and Clinical Research Unit of the German Research Foundation.
Kovacs G, et al: J Clin Oncol. August 29, 2016 (early release online). ■
