Understanding Frontline Therapy Pattern, Attrition Rates and Survival Outcomes in Patients with Newly Diagnosed Multiple Myeloma Who Underwent Transplant

Introduction: Given the incurable nature of multiple myeloma (MM), the therapy goals are to achieve best possible response, delay disease progression, and prolong survival. For young (<70 years) and fit patients, induction therapy followed by autologous stem cell transplantation (SCT) remains the standard of care. This study aims to understand the frontline (1L) therapy pattern, attrition rates, and outcomes for patients with newly diagnosed MM (NDMM) who underwent SCT during 1L in the real-world setting. Methods: The study sample included adults with NDMM identified in the Flatiron Health EMR database (January 1, 2016 - October 31, 2023) who had the first MM diagnosis on or after January 1 2016; no MM therapy/SCT in the year prior to MM diagnosis; ≥1 MM therapy within 6 months of MM diagnosis; no participation of clinical trial; and received SCT during 1L. The index date was defined as the date of 1L initiation. Lines of therapy (LOTs) and regimens were inferred from EMR records of MM-recommended agents (e.g., bortezomib [V], lenalidomide [R], daratumumab [D]). Dexamethasone (d) was assumed to be included in all regimens. Demographic and clinical characteristics were summarized in the year prior to index date. Frontline regimens, time from 1L start to SCT, and attrition rates post-1L (defined as the proportion of patients who discontinued prior LOT without record of subsequent LOT) were described. Time to event outcomes after 1L start, including time to LOT discontinuation or death (LOT duration), real-world progression-free survival (rwPFS], and overall survival (rwOS), were analyzed using Kaplan-Meier (KM) method. Results: This study identified 1,544 patients with MM who received SCT during 1L. The median age was 62 years (54.3%, 23.5%, and 17.8% in age groups 45-64, 65-69, and ≥70 years, respectively), 55.2% were male, and 64.8% were White. The mean (standard deviation) number of CRAB symptoms was 1.05 (0.92): anemia was the most prevalent MM symptom (61.9%), followed by renal impairment (19.6%) and hypercalcemia (19.6%). Among the 829 patients with non-missing Eastern Cooperative Oncology Group performance status (ECOG) information, 10.7% had ECOG ≥2, 41.3% had ECOG 1, and 48.0% had ECOG 0. Among 1,127 patients who had information on International Staging System (ISS), 44.9%, 29.6%, and 25.5% had ISS Stage I, II, and III, respectively. Cytogenetic information was available for 958 patients, a third (32.3%) of whom had high-risk cytogenetics. The most common 1L induction regimens were VRd (52.3%), Rd (17.4%), and DVRd (10.0%), with the remaining 20.3% using other regimens. Median (95% confidence interval [CI]) time from 1L start to SCT was 5.9 (5.8-6.1) months and maintenance therapy was observed in 864 (56.0%) patients post-SCT. The KM-based median (95% CI) duration of 1L treatment was 21.7 (19.4-24.0) months, and median rwPFS and median rwOS were not reached for 1L. During a median follow-up of 37.9 months after 1L start, 524 (33.3%) patients had discontinued 1L but did not initiate 2L and 10 (0.7%) patients died on 1L, corresponding to an attrition rate of 33.9%. For 2L patients, the KM-based median (95% CI) duration of therapy was 15.2 (12.6-17.7) months and median (95% CI) rwPFS was 60.1 (50.2-NR) months. Among the 654 patients who initiated 2L, 141 (21.6%) patients discontinued 2L but did not have evidence of 3L and 18 (2.8%) patients died on 2L, corresponding to an attrition rate of 24.3% from 2L to 3L. For 3L, the KM-based median (95% CI) duration of therapy was 8.6 (7.1-11.0) months and the median (95% CI) rwPFS was 27.6 (16.6-46.6). The estimated 5-year rwOS rates were 83.9% (81.1-86.3), 69.3% (62.1-75.4), and 48.2% (35.4-59.9) for 1L, 2L, and 3L, respectively. Conclusions: Despite advancement in treatment for MM, a considerable number of patients who underwent SCT did not receive subsequent LOTs, evidenced by substantial attrition rates. In addition, shorter duration of therapy, higher risk of disease progression, and worsening survival outcome were observed with each additional LOT. The findings underscore the importance of using the most efficacious regimens upfront to achieve deep and durable response that translates into longer remission and survival.