The prognostic impact of minimal residual disease in patients with chronic lymphocytic leukemia requiring first-line therapy

A proportion of patients with chronic lymphocytic leukemia achieve a minimal residual disease negative status after therapy. We retrospectively evaluated the impact of minimal residual disease on the outcome of 255 consecutive patients receiving any front-line therapy in the context of a detailed prognostic evaluation, including assessment of IGHV , TP53 , NOTCH1 and SF3B1 mutations. The median follow-up was 73 months (range, 2–202) from disease evaluation. The median treatment-free survival durations for patients achieving a complete response without or with minimal residual disease, a partial response and no response were 76, 40, 11 and 11 months, respectively ( P <0.001). Multivariate analysis revealed that three variables had a significant impact on treatment-free survival: minimal residual disease ( P <0.001), IGHV status ( P <0.001) and β2-microglobulin levels ( P =0.012). With regards to overall survival, factors predictive of an unfavorable outcome were minimal residual disease positivity ( P =0.014), together with advanced age ( P <0.001), unmutated IGHV status ( P =0.001), TP53 mutations ( P <0.001) and elevated levels of β2-microglobulin ( P =0.003). In conclusion, for patients requiring front-line therapy, achievement of minimal residual disease negativity is associated with significantly prolonged treatment-free and overall survival irrespective of other prognostic markers or treatment administered.