P-175: Real-world minimal residual disease testing patterns: findings from the Connect® MM Registry

Introduction: Treatment advances in multiple myeloma (MM) are helping patients (pts) achieve deep remission. As such, the traditional criteria for assessing complete remission may no longer be adequate. Minimal residual disease (MRD) status post treatment is a strong and independent prognostic factor in MM (Szalat R, et al. Haematologica 2024; doi:10.3324/haematol.2023.284662) that was recently recognized as a viable endpoint in clinical trials by the FDA’s Oncologic Drugs Advisory Committee (Apr 12, 2024; www.fda.gov/advisory-committees). However, the timing and method of testing are not yet standardized. This analysis assessed MRD testing patterns and explored prognostic signals associated with MRD status in a real-world cohort of pts with MM.

Methods: The Connect^® MM Registry (NCT01081028) is a large, prospective, US observational cohort study of newly diagnosed pts with MM enrolled from Sep 2009 to Apr 2016. Pts with evidence of at least one MRD test from Sep 28, 2009 to Feb 7, 2024 were included in this analysis. Data collected included MRD date, method, and sensitivity; baseline demographics; clinical characteristics; and treatment patterns. All were analyzed descriptively. Time to next treatment (TTNT) from the first MRD test was estimated using the Kaplan-Meier method with start of a new line of therapy as the event and death, study discontinuation, or Feb 7, 2024 as censoring events.

Results: Among the Connect MM cohort, comprising approximately 3011 pts, 82 (2.7%) had undergone MRD testing. The median age of pts undergoing MRD testing was 61.5 years, and most (61.0%) had Eastern Cooperative Oncology Group performance status score of 0–1 at Registry enrollment. Among these 82 pts, a total of 119 MRD tests had been carried out. Around half (49.6%) of all tests were MRD negative, 41.2% of tests were MRD positive, and 9.2% had an unknown result. The most frequently recorded test sensitivity was 10^-6 (22.7%) and the majority of tests were carried out using flow cytometry (81.5%). Around 1 in 4 (26.1%) tests were carried out in pts enrolled in a clinical trial. Most commonly, the MRD tests were carried out during the first line of therapy (41.2%), with lenalidomide, bortezomib plus dexamethasone (RVd) being the most common regimen (16.0%) received by pts in the line where the MRD test was conducted. Median TTNT was longer in pts who were MRD negative (51.2 months) versus MRD positive (4.1 months) at the first MRD test. Around 50.0% of MRD-positive pts initiated a new regimen within 3 months of the first MRD test, compared with only ~ 6.0% of MRD-negative pts.

Conclusions: This analysis of pts in the Connect MM Registry provides the largest dataset of real-world MRD testing patterns available to date, with enrollment from 2009–2016. MRD testing was uncommon, except as part of a clinical trial. MRD status assessment was not considered standard of care in real-world settings. As such, only a small proportion of pts with MM underwent MRD testing in clinical practice.