Data presented at the International Myeloma Society (IMS) annual meeting held September 27–30 in Athens, Greece, focused on 3 main topics: (1) the use of newer agents, (2) optimizing outcomes, and (3) the use of minimal residual disease (MRD) measurements to predict long-term outcome for patients or to potentially stop maintenance therapy.
Patients achieving sustained MRD negativity at 3 years post-maintenance initiation may be able to discontinue lenalidomide maintenance, according to data presented at IMS. The study enrolled 151 NDMM patients who underwent ASCT, with 42 patients successfully discontinuing lenalidomide maintenance after 3 years of sustained MRD negativity. The researchers found that MRD negativity was maintained in most patients at various time points post-discontinuation. Six months after discontinuation of lenalidomide maintenance, 39 out of 41 patients were MRD negative. At 12 months, 36 out of 38 patients continued to be MRD negative. At 18 months, all evaluable patients (n=18) remained MRD negative. At 24 months, 13 out of 14 patients were MRD negative, and at 30 months all 4 evaluable patients were MRD negative. Overall, 5 patients restarted treatment with lenalidomide monotherapy after converting from MRD negative to MRD positive following the initial completion of maintenance. One patient progressed and received second-line treatment. “Sustained MRD negativity after 3 years of lenalidomide maintenance may guide the safe discontinuation of maintenance, though this has to be proven in prospective randomized clinical trials,” the researchers note.
A predictive model involving 3 measurable risk factors in MM—ISS stage, circulating tumor cell (CTC) levels, and time to first MRD negativity—may help identify TE patients with risk factors that can predict disease recurrence. A total of 267 patients out of 458 who attained MRD negativity by next-generation flow cytometry were analyzed over a median follow-up of 73 months. The patients in this analysis had been enrolled in the GEM2012MENOS65/GEM2014MAIN clinical trials. Results showed that 54% of patients maintained MRD negativity, 42% experienced MRD resurgence or progressive disease, and 4% died without progression. Prognostic factors at diagnosis, including ISS stage III and ≥0.01% CTCs, were found to predict MRD resurgence or progression, whereas patients achieving MRD negativity sooner, particularly after induction (<6 months), exhibited a lower risk of MRD resurgence or progression. A dynamic model incorporating ISS stage, CTC levels, and time to first MRD negativity assessment demonstrated predictive potential. Five-year rates of MRD resurgence or progression in patients with no, one, or ≥2 risk factors were 16%, 33%, and 57%, respectively. According to the researchers, this model could aid in both clinical trial design and routine practice decision-making.
Serial MRD testing within the first 5 years after diagnosis may help predict long-term outcomes. Data presented at IMS included 1,744 NDMM patients who underwent single or tandem ASCT. Patients were categorized into 3 groups based on their MRD test results in the initial 5 years of treatment. Group 1, which included patients with 3 serial MRD-negative tests, demonstrated an encouraging long-term outcome, with a 10-year PFS of 74%. By contrast, Group 2 included patients with both negative and positive MRD tests and exhibited a 10-year PFS of 30%. Group 3, with consistent MRD-positive tests, had a 10-year PFS of 1%. This study suggests that achieving and maintaining serial MRD negativity in the early years of myeloma treatment may predict excellent long-term outcomes, offering potential guidance for clinical practice and trials. According to the researchers, “achievement of 3 serial MRD-negative tests in the first 5 years of therapy is predictive of an excellent long-term outcome with few treatment failures.”
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This educational activity is supported by educational grants from AbbVie Inc., Bristol Myers Squibb, and GSK, and sponsorship from Legend Biotech USA Inc.
