Clinical Director Myeloma Service Memorial Sloan Kettering Cancer Center NY, New York, United States
Introduction: Lenalidomide maintenance (LM) therapy is a cornerstone therapeutic strategy in multiple myeloma (MM) patients (pts), prolonging remissions and extending overall survival. Long-term analysis of the UK Myeloma XI trial has suggested that the benefit of continuing maintenance in pts with sustained minimal residual disease (MRD) negative (neg) status beyond 3 years, is unclear (Pawlyn et al. ASH 2022. Abs# 570). We present updated results from a prospective phase II study of LM discontinuation in MM patients after >3-years of sustained MRD neg remission while on LM.
Methods: This phase II study (n=50) evaluates MRD dynamics following LM discontinuation in pts who have demonstrated >3 years of durable MRD neg responses. Enrolled pts stop LM and undergo surveillance with serum and clinical follow-up (f/up) every 3 months, bone marrow MRD testing by multiparametric flow cytometry (single 10-color tube with limit of detection of at least 6x106 with at least 3 million cell acquisitions, meeting IMWG criteria) every 6 months, and annual PET-CTs for 3 years. Primary endpoint is sustained MRD neg rate after 1 year, while secondary endpoints are sustained MRD neg rate at 3 years of cessation, re-treatment responses, microbiome and immune studies, health-related quality of life outcomes, and progression-free survival (PFS).
Results: From February 2020 to March 2024, a total of 43 pts enrolled onto the study. The median f/up is 21.2 mo (17-32). Median time since diagnosis is 8.1 years (4-20), and median duration of maintenance therapy is 56.3 mo (33-161). Pts enrolled included 31(72%) ISS-I, 9(21%) ISS-II, 2(5%) ISS-III, 1(2%) stage not reported (NR), 6(14%) high-risk (HR) cytogenetics [t(4,14), t(14,16), +gain 1q21.3], and 4(9%) cytogenetics NR. After stopping LM, 26/31(84%) remained MRD neg at 12 months. Patients with a durable MRD neg response at 24 mo was 82% (95% CI 69-96%), and PFS at 24 mo was 91% (95% CI 81-100%). Durable MRD neg response at 24 mo for standard risk (SR) vs. HR or NR pts was 87% (95%CI 74-100%) vs. 66% (95% CI 40-100%) (p=0.058). Among MRD pos convertors, 4/9 had clinical progression requiring alternative therapy than LM, while 5/9 remained asymptomatic with MRD conversion. Three asymptomatic MRD convertors restarted LM; subsequent testing demonstrated 1 pt remained MRD pos while 1 pt recaptured MRD neg.
Conclusions: Current results suggest LM cessation among SR patients who have sustained MRD neg remissions for >3 years is feasible and associated with low rates of clinical progression. Ongoing efforts, studying MRD dynamics, immune biomarkers, and patient quality of life are underway with the potential to guide earlier treatment discontinuation and thereby define functional cure in MM.
