Minimal Residual Disease in Chronic Lymphocytic Leukemia

Minimal residual disease (MRD) is commonly detected in chronic lymphocytic leukemia (CLL) using four-color flow cytometry, states Jennifer Brown, MD, PhD. It is a useful marker that can help indicate an appropriate time to stop therapy, says Javier Pinilla-Ibarz, MD, PhD. While it is not yet clinically standardized, there are data showing that patients with CLL who become MRD-negative demonstrate longer progression-free survival and overall survival compared with those not MRD-positive.

Data from MD Anderson Cancer Center demonstrated that patients who were MRD-negative at the end of 3 cycles of fludarabine, cyclophosphamide, and rituximab (FCR), fared neither better nor worse than those who were MRD-negative at the end of 6 cycles, notes William Wierda, MD, PhD. Patients who achieve MRD-negativity after 3 cycles of FCR should be followed using a computed tomography (CT) scan. If there is no evidence of enlarged lymph nodes or other markers of disease, treatment can safely be discontinued. Current data suggest that 3 additional chemotherapy cycles may incur more toxicity than benefit, says Wierda.

Although achieving MRD-negativity with FCR is associated with better outcomes, it remains unclear whether adding more treatment for the sole purpose of achieving MRD-negativity is superior, explains Brown, noting that it may be a marker of better overall disease risk rather than improving survival.

Most patients do not achieve complete remission with treatment from novel B-cell receptor (BCR) pathway inhibitors. Many individuals still have macroscopic disease, and the value of MRD for these treatments has been questioned, comments Brown.

Patients may be able to receive treatment breaks, if future studies demonstrate that novel inhibitors in combination with other medications result in deeper remissions. Patients may avoid developing drug-resistant disease if they relapse while on treatment holiday, while they will certainly develop resistance if they relapse while receiving ongoing treatment, says Brown.