MM-233 Evaluation of the Comparative Effectiveness of In-Class Transition (iCT) to All-Oral Ixazomib-Lenalidomide-Dexamethasone (IRd) After Bortezomib (V)-Based Induction Therapy vs Patients Who Continued to Receive Parenteral V-Based Therapy in Newly Diagnosed Multiple Myeloma (NDMM)

Context: Increasing the duration of proteasome inhibitor-based treatment could improve outcomes in NDMM patients. Objective: To evaluate the comparative effectiveness of in-class transition (iCT) to IRd following V-based induction vs continued V-based therapy. Design: A secondary analysis of patients from US MM-6, (NCT03173092; Manda CLML 2020; phase IV, single-arm study) which is evaluating iCT from parenteral V to all-oral IRd (‘IRd’ cohort), and a comparator (‘V-based‘) cohort of patients from INSIGHT MM (Costello Future Onc 2019; prospective, observational study) who continued to receive V-based therapy. Setting: Routine community clinical practice in the US. Patients: Non-transplant-eligible NDMM patients with ≥stable disease after 3 cycles of V-based induction and Eastern Cooperative Oncology Group performance status (ECOG PS) ≤2 from US MM-6 (IRd cohort, n=100) and INSIGHT MM (V-based cohort, n=111). Main Outcome Measures: First-line duration of treatment (DOT), overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and reasons for treatment discontinuation. Kaplan–Meier methodology was used for time-to-event outcomes. To reduce imbalances between cohorts, inverse probability of treatment weighting (IPTW) was used. Results: Results are presented as IRd vs V-based cohorts. After IPTW, median age was 75.0 vs 74.8 years; 56.7 vs 51.3% of patients were male, 37.4 vs 29.1% had ECOG PS of 2, and 48.8 vs 41.4% were International Staging System stage III at diagnosis. Initial induction therapy was VRd/V-cyclophosphamide (C)-d/VRCd in 79.5/17.7/2.8 vs 77.3/19.5/3.1% of patients. ORRs were 73.2 (95% confidence interval [CI]: 65.0–81.3) vs 57.5% (95% CI: 47.9–67.1; p<0.0001). Median DOT was 10.8 (95% CI: 6.5–24.4) vs 5.3 months (95% CI: 4.3–7.0; p<0.0001; median follow-up, 20.3 vs 15.8 months). Median PFS and OS were not estimable in either cohort. 24-month PFS rates were 85.7 (95% CI: 68.1–94.0) vs 76.5% (95% CI: 62.6–85.8). 24-month OS rates were 94.0 (95% CI: 77.7–98.5) vs 84.9% (95% CI: 70.6–92.6). Overall, 17.6% discontinued IRd and 24.4% discontinued V due to an adverse event. Conclusions: In NDMM patients treated at US community oncology clinics, those who transitioned to IRd following 3 cycles of V-based induction had significantly higher ORR and longer DOT than those who continued to receive V-based therapy.