Assessment of Measurable Residual Disease (MRD) in Chronic Lymphocytic Leukemia (CLL) and Multiple Myeloma (MM) Among U.S. Community Hematologists/ Oncologists (cH/O)

Introduction: In this era of targeted therapy, assessing MRD status is important to guide treatment decision-making in hematologic malignancies. While MRD assessment has long been incorporated the management of patients with acute lymphoblastic leukemia (ALL), there is mounting evidence that MRD-negativity is a critical end point in CLL and MM that correlates well with clinical outcomes. In CLL, undetectable MRD at the end of treatment in peripheral blood or bone marrow is associated with long-term survival (Thompson et al, Leukemia 2018). The international workshop on CLL (iwCLL) guidelines for response assessment in CLL now incorporate MRD assessment (Hallek, et al, Blood 2018). The international myeloma working group (IMWG) and the NCCN now recommend MRD assessment after each phase of MM therapy (induction, stem cell transplant, consolidation and maintenance). Higher rates of durable responses are noted in those with MRD-negativity after induction (Attal et al, NEJM 2017) and associated with favorable survival (Pavia et a, Blood 2008). Based on results from recent studies, MRD negative status can guide clinical decision-making about discontinuation of therapy in CLL (Jain et al, ASH 209 and Tam et al, ASH 2019) and in MM (Costa et al, ASH 2019 and Usmani et al, 2019). A majority of patients with CLL and MM are treated at community practices in the US. but adoption of MRD assessment among cH/O is unclear. We sought to study the self-reported utilization patterns of MRD assessment in CLL and MM, it's use in determining duration of therapy, and the barriers to it's adoption in practice among U.S. cH/O.

Methods: U.S.-licensed oncologists and hematologists with broad geographic representation convened at a live meeting in January 2020 to review clinical updates presented at the 2019 ASH Annual Meeting. An electronic pre-meeting survey and live survey were fielded among cH/O meeting attendees. Surveys collected physician perceptions and reported use of MRD assessment for patients with CLL and MM. Responses to questions were summarized using descriptive statistics.

Results: A total of 59 cH/O were included who self-identified their specialty as hematology/ oncology (51%) and medical oncology (34%) and reported MM (69%) and CLL (61%) as the two commonest hematologic malignancies treated by them. Excluding those that had not treated MM or CLL in the preceding 3 months, a subset of 46 cH/O were queried on their use and perceptions of MRD assessment in these two diseases. In CLL, 52% of the cH/O do not assess MRD status, and only 17% utilize MRD status in treatment discontinuation decisions. Major reasons for not using MRD status in practice include the perception shared by a majority (52%) of respondents that the evidence does not support its use in CLL at the present time. A minority (9%) utilized MRD assessment when treating younger fit patients with CLL. In MM, 50% do not assess for MRD at any time post-therapy, and 24% utilize MRD status in treatment discontinuation decisions. Major barriers to MRD assessment in MM were the perception that evidence does not support MRD use (59% of the respondents) and lack of payer coverage (11%). Additional details are presented in the Table below.

Conclusions: These data from a limited sample of cH/O suggest that adoption of MRD testing among US cH/O is low, despite results from recent trials that highlight the importance of the MRD negativity as an important prognostic factor in both CLL and MM. Half of cH/O do not measure MRD at any point while treating MM and CLL and less than a fifth incorporate MRD data to determine duration of therapy. The greatest barrier to MRD assessment is the impression that there is lack of evidence supporting its utility in practice at the present time. Further education among cH/O is warranted regarding MRD assessment in CLL and MM given that MRD-negative status is associated with favorable prognosis and should be incorporated in treatment decision-making based on updated guidelines in both diseases.

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