MRD Status Helped Predict Outcomes in CLL Responders

The quantification of a patient’s minimal residual disease (MRD) after treatment for chronic lymphocytic leukemia (CLL) allowed for a more specific prediction of progression-free survival among patients who responded to treatment, according to the results of a new study published in the Journal of Clinical Oncology.

For example, data showed that patients who had an MRD-negative partial response had a longer progression-free survival than patients with MRD-positive complete response. In addition, there was no difference in progression-free survival found between patients who were MRD-negative who had achieved complete response and those who achieved partial response.

“The enhanced ability to identify good-risk patients supports the use of MRD assessments of all responders as an efficacy endpoint in clinical trials for CLL,” wrote Gabor Kovacs, MD, of the University of Cologne and Center of Integrated Oncology Cologne-Bonn, Cologne, Germany, and colleagues. “Defining MRD negativity for patients who achieved complete response only-as currently recommended in the European Medicines Agency guideline-would arbitrarily assign [many good-risk] patients (29.1% of patients with MRD-negative partial response in our analysis) to a poor risk category.”

The 554 patients included in this study were taken from two randomized trials of the German CLL Study Group: CLL8, which compared fludarabine and cyclophosphamide with or without rituximab, and CLL10, which compared fludarabine plus rituximab compared with bendamustine plus rituximab. MRD was assessed in peripheral blood at a threshold of 10^-4.

The median progression-free survival in the study from the end of treatment landmark was 61 months for patients with MRD-negative complete remission; 54 months for patients with MRD-negative partial response; 35 months for MRD-positive complete remission; and 21 months for MRD-positive partial response. The progression-free survival was significantly longer in patients with MRD-negative partial response than in MRD-positive complete remission (P = .048) and for patients with MRD-positive complete remission compared with MRD-positive partial response (P = .002).

A median progression-free survival was not reached for patients with MRD negativity compared with an estimate of 36 months for patients with MRD-positive complete remission and 25 months for MRD-positive partial response.

The researchers also evaluated differences in overall survival between these groups. They found that only those patients with MRD-negative complete remission had significantly longer overall survival compared with MRD-positive partial response (not reached vs 72 months; P = .001). No difference in overall survival was found between MRD-negative partial response and MRD-positive complete remission.

Among patients who were MRD-negative, the researchers found that patients with partial response who presented with residual splenomegaly had a similar progression-free survival to those patients with complete remission (63 months vs 61 months).

“We hypothesize that residual splenomegaly after chemo(immuno)therapy often represents tissue that does not contribute to a subsequent clinical progression,” the researchers wrote.

However, they found that patients with MRD-negative partial response with lymphadenopathy had significantly shorter progression-free survival (31 months; P < .001). According to the researchers, these patients “might be prone to faster regrowth of the disease from the lymph nodes even if they had achieved an MRD-negative status in peripheral blood.”