Discontinuation of maintenance therapy in multiple myeloma guided by multimodal measurable residual disease negativity (MRD2STOP).

person Benjamin Avi Derman University of Chicago, Chicago, IL info_outline Benjamin Avi Derman, Jennifer H. Cooperrider, Tadeusz Kubicki, Ajay Major, Ken Jiang, Aubrianna Ramsland, Karson Buckley, Samrawit Melka, Amanda McIver, Theodore Karrison, Andrzej J. Jakubowiak

Authors person Benjamin Avi Derman University of Chicago, Chicago, IL info_outline Benjamin Avi Derman, Jennifer H. Cooperrider, Tadeusz Kubicki, Ajay Major, Ken Jiang, Aubrianna Ramsland, Karson Buckley, Samrawit Melka, Amanda McIver, Theodore Karrison, Andrzej J. Jakubowiak Organizations University of Chicago, Chicago, IL, University of Chicago, Department of Medicine, Chicago, IL, University of Chicago Medical Center, Chicago, IL, Division of Hematology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, Department of Medicine, University of Chicago Medical Center, Chicago, IL Abstract Disclosures Research Funding No funding sources reported Background: Measurable residual disease (MRD) negativity is a potential marker for the absence of disease in multiple myeloma (MM), which could be used to guide treatment cessation. MRD2STOP (NCT04108624) is a prospective study investigating outcomes among patients with sustained multimodal MRD negativity who discontinue maintenance therapy. Methods: Discontinuation of maintenance was permitted if MRD negative by PET/CT, flow cytometry (limit of detection [LoD] 10-5), and NGS by clonoSEQ (threshold 10-6). Patients underwent serial blood testing along with clonoSEQ, flow, and PET/CT annually for 3 years. Concurrent BM aspirate samples also underwent CD138+ immunomagnetic enrichment analyzed using clonoSEQ to achieve MRD 10-7 sensitivity. Primary endpoints were MRD resurgence rate at the 10-6threshold, along with progression-free survival (PFS) and overall survival among those MRD negative by the standard non-enriched clonoSEQ. Results: 83 patients were screened, and 47 patients met eligibility to discontinue maintenance as of 1/21/24. Median age was 66 years (range 39-84). 17 (36%) had high-risk disease at diagnosis (8 with 1q copy abnormalities, 5 with ISS stage 3, 2 with t(4;14), 1 with t(14;16), and 3 with del17p). Most (45/47, 96%) had one line of therapy; 26 (55%) received a triplet and 19 (40%) a quadruplet. Prior autologous transplant was received by 30 (64%) and multi-drug consolidation in 36 (77%) prior to single-agent maintenance. 96% received lenalidomide as maintenance. Median duration of consolidation/maintenance therapy prior to discontinuation was 36 months (range 12-95), including 14 (30%) with <27 months. Median follow-up was 30 months. Of 47 enrolled patients, 5 (11%) experienced disease progression and an additional 6 (13%) had MRD resurgence at 10-6. Of 11 MRD resurgent events, 4 (36%) were MRD 10-7 positive at baseline, and 3 (27%) were MRD 10-7 positive 1 year prior to MRD 10-6 resurgence. 2 second hematologic cancers occurred during follow-up: 1 Hodgkin lymphoma and 1 B-ALL, the latter which resulted in the only patient death on study. The estimated 3-year PFS was 85%, including 93% for patients MRD 10-7 negative (n=40) at baseline and 31% for those MRD 10-7 positive (n=7) at baseline (logrank p<0.001). Among the MRD evaluable patients (n=45), the 3-year MRD-free survival (MRD-FS) was 68%; 78% for patients MRD 10-7 negative (n=38) and 33% for patients MRD 10-7 positive (n=7) (logrank p<0.001). There were no differences in MRD-FS or PFS when stratified by high-risk disease, receipt of transplant, consolidation, or duration of maintenance. Conclusions: Discontinuation of maintenance therapy among patients with MM and multimodal MRD-negativity results in a high rate of sustained MRD-negativity and lack of disease progression. CD138+-enriched MRD samples using the clonoSEQ assay may help to even better identify patients who can discontinue therapy. Clinical trial information: NCT04108624.

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