Panel Offers Consensus Recommendations for MRD Assessment in CLL

The recommendations come at a time when treatments for chronic lymphocytic leukemia (CLL), such as venetoclax, are making deep remissions and undetectable minimal residual disease (MRD) after a fixed duration of treatment feasible goals.

In an effort to standardize the assessment of measurable (or minimal) residual disease (MRD), a group of researchers has summarized key recommendations from a multidisciplinary panel that answer key questions surrounding the approach increasingly being utilized in chronic lymphocytic leukemia (CLL).

The recommendations come at a time when treatments for CLL, such as venetoclax, are making deep remissions and undetectable MRD after a fixed duration of treatment feasible goals. They were published in a recent issue of Leukemia.

“The current utility and future potential of MRD in CLL underscore the need to use standardized, validated assays; adopt a routine, unambiguous nomenclature; and report assay results systematically. This international panel was convened to provide expert guidance on these issues,” the authors wrote.

Recommending only validated assays for assessing MRD, the panel highlighted the ERIC-compliant flow cytometry and EuroMRD-compliant real-time quantitative polymerase chain reaction tests, although they note that assay choice should be determine based on the rationale for MRD assessment. For example, evaluating the impact of curative approaches on MRD may require the most sensitive test available.

The timing and frequency of treatment also depend on the type of treatment, the recommendations say:

  • For fixed-duration treatment: Align testing with response assessment at least 2 months following completion of treatment
  • For continuous treatment: Testing should be done when best clinical response is achieved

The panel notes that MRD assessment should include patients who achieve a partial response, not just those who achieve a complete response, as patients with a PR may achieve undetectable MRD (U-MRD).

“In first-line chemoimmunotherapy treatment of CLL, MRD status was independently associated with extended treatment-free survival, progression-free survival, and overall survival,” explained the group. “U-MRD is more accurately associated with survival than conventional responses after first-line chemoimmunotherapy. In this setting, patients achieving U-MRD and partial response may have a prognosis superior to that of MRD-positive patients achieving complete response.”

They also note that the relationship between clinical response and MRD following treatment is complicated and further research is needed. For example, this relationship may differ based on treatment strategy, and end-of-treatment MRD and survival outcomes may be dependent on other factors.

They add that although evidence suggests that MRD is associated with survival outcomes, no prospective trials to date have established U-MRD as a surrogate end point for time-to-event end points, highlighting a need for trials that validate MRD as a surrogate for end points, like progression-free survival, specific to treatment.

Reference

Wierda W, Rawstron A, Cymbalista F, et al. Measurable residual disease in chronic lymphocytic leukemia: expert review and consensus recommendations. Leukemia. 2021;35(11):3059-3072. doi:10.1038/s41375-021-01241-1