Novel agents were introduced into the TT clinical trials as they became available and were integrated with standard treatments for off-trial patients when medically appropriate (supplemental Figure 1). Patients eligible for inclusion in this study presented at the University of Arkansas for Medical Sciences (UAMS) Myeloma Center with newly diagnosed MM and received ASCT between 19 as part of their first-line therapy. The increased likelihood of patients successfully achieving MRD-negative status raises the question of whether MM patients receiving optimized treatment could attain “functional” or “operational” cure, 10-12 which contrary to eradication cure, is defined as the adequate suppression of residual malignant cells to achieve sustained disease control. 3-9 Consistent with improved outcomes and therapeutic advancements, the therapeutic goal has also changed, with a major emphasis on maximizing the depth of response to delay relapse and achieve long-term disease control. These studies reported better complete response (CR), increased rates of minimal residual disease (MRD) negativity, and improved progression-free survival (PFS) for the patients receiving the combinations. However, results differed depending on age, risk group, and cytogenetic characteristics.Īutologous stem cell transplantation (ASCT) is an important component of modern therapy, and a number of studies have compared survival for newly diagnosed MM patients treated with ASCT and novel agents to novel agent combinations alone. There was some evidence of reductions in early mortality within 3 years of diagnosis, longer complete response (CR) duration, and reductions in relapse after achieving CR. Cure models support the potential for cure, ranging from 6.3% to 31.3%, depending on the year of treatment, with 10.0% to 18.6% of patients achieving their normal life expectancy across multiple periods. Patients treated during intervening time periods often had intermediate survival, but trends in OS, PFS, and landmarked analyses were inconsistent. Steady improvements in OS were found, with patients treated in 2014 or later having superior OS (hazard ratio, 0.35 95% confidence interval, 0.27-0.45) and reduced excess risk for MM death (relative excess risk, 0.30 95% CI, 0.22-0.41) compared with patients treated in 1997 or earlier. Overall survival (OS) and progression-free survival (PFS) were evaluated using Kaplan-Meier analysis, Cox proportional hazards models, relative survival analysis, and cure modeling among different time periods, risk groups, and demographic traits. To examine improvements in long-term survival, we followed 4329 patients with newly diagnosed MM treated with autologous stem cell transplantation (ASCT) at the University of Arkansas for Medical Sciences from 1989 through 2018. However, improvements in treatments has raised the possibility that MM might be functionally curable. Traditionally, MM is considered an incurable disease, with most patients eventually relapsing. As multiple myeloma (MM) treatments evolve, frequent updates are required to monitor the long-term effect of changes in approach.
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