Comparative Effectiveness of Triplets Containing Bortezomib (V), Carfilzomib (K), or Ixazomib (I) Combined with a Lenalidomide and Dexamethasone Backbone (Rd) in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) in Routine Care in the United States (US)

• Published in: Blood 2019-11, Vol.134 (Supplement_1), p.1827-1827
• Main Authors: Chari, Ajai, Romanus, Dorothy, Raju, Aditya, Cain, Lauren, Blazer, Marlo, Farrelly, Eileen, Stull, Dawn Marie, Ailawadhi, Sikander
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2019-121658

BACKGROUND: Proteasome inhibitors (PIs) combined with an Rd backbone constitute commonly used regimens in RRMM in the US. Lack of data from head-to-head clinical trials comparing the efficacy of these PI-Rd triplets and the extent to which efficacy translates to benefit in routine care highlight the need for real-world evidence. We conducted a comparative effectiveness analysis of time to next therapy (TTNT) of these PI-Rd triplet combinations in a real-world representative cohort of RRMM patients. METHODS: In this retrospective cohort study, RRMM patients who initiated an index regimen with IRd, KRd, or VRd in ≥2nd line of therapy (LOT 2+) were followed between 1/2014-9/2018 in Optum's deidentified national electronic health records database. This database captures information on all patients treated by >140,000 providers across 50 states in the US. It is representative of the US general population. Baseline data included: a modified frailty score utilizing age and Charlson Comorbidity Index1, ECOG performance status, CRAB symptoms, ISS stage, cytogenetic risk (high: del[17p], t[4;14], or t[14;16]), history of: cardiovascular disease, peripheral neuropathy, stem-cell transplant, and uncontrolled hypertension, prior PI and/or IMID exposure and refractory status, time from diagnosis to start of index LOT, time from start of frontline therapy to start of LOT 2, and treatment-free interval prior to index LOT. Duration of therapy (DOT) and TTNT were estimated using Kaplan-Meier methods and compared using stratified (by LOT) ± baseline-adjusted Cox proportional hazard models with a repeated measures analysis of pt-LOTs with robust sandwich estimators to account for inclusion of patients in multiple LOTs. The main analysis was repeated in subgroups a priori defined by frailty score, cytogenetic risk, prior PI and/or IMID exposure and LOT. Observations were censored at time of loss to follow up/end of study period (9/30/2018). RESULTS: Overall, 650 patients with 733 pt-LOTs (IRd, n=168; KRd, n=208; VRd, n=357) were included; 20% of the RRMM patients in this cohort were treated at academic centers. In the I-/K-/V-Rd groups, respectively, median age was 71/65/71 years and 42/22/38% patients were ≥75 years old; 39/55/46% and 28/14/29% patients had a modified frailty score of intermediate and frail, respectively; 71/88/80% had a symptomatic relapse with at least 1 CRAB symptom; 20/28/13% patients had high cytogenetic risk; 69/72/90% patients were treated in 2-3 LOT,