Larysa Sanchez, MD from Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute speaks about the ASH 2020 Abstract – 3242 Real-World Treatment Patterns and Outcomes of Proteasome Inhibitor (PI: Bortezomib [V], Carfilzomib [K], or Ixazomib [I])-Lenalidomide/Dexamethasone (Rd)-Triplets By Prior Lenalidomide-Exposure in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) Engaged in Routine Care in the United States (US)
REFERENCE:
The most frequently used triplet combination regimens in patients (pts) with RRMM in the US are PIs paired with a Rd backbone. The hallmark research supporting the effectiveness of these regimens were primarily in pts without prior exposure to lenalidomide (R).1,2 Real-world studies have shown that R-based regimens are increasingly used in the front-line environment.3-5 Therefore, real-world treatment trends in pts with prior R exposure and comparative real-world efficacy of PI-Rd triplets with RRMM nee in this population
AND METHODS:
In Optum’s de-identified national electronic health records database, a retrospective cohort of RRMM pts initiating IRd, KRd, or VRd in line of therapy (LOT) al 2 was followed from 7/2007-9/2018. Between 1/2014 and 9/2018, RRMM pts were identified as those initiating LOT ⇠2 and were listed in any previous LOT as having or not having prior exposure to R (R-exposed; no-prior-R). The first implementation of the I-/K-/or V-Rd was the index regimen. In accordance with the NCCN MM Guidelines, LOTs were identified by an algorithm developed with MM specialists to proxy the definition of LOT in RCTs &.6 Baseline data included: CRAB (hypercalcemia, renal failure, anemia, and bone lesions); high-risk cytogenetics (defined as del[17p], 1q21 benefit, t[4;14], or t[14;16]); Charlson Comorbidity Index (CCI) score; and adjusted frailty score using age and age. The median length of therapy (DOT) and time-to-next-treatment (TTNT) (a PFS proxy; defined as the time from the beginning of the index regimen to subsequent LOT or death) were calculated using Kaplan-Meier methods and compared using proportional hazard models of covariate-adjusted Cox (FIGURE). Observations at the time of follow-up failure (f/u)/end of the study period (9/30/2018) were censored.
RESULTATIONS:
Of the 650 pts included, R-exposed was 397 (IRd, n=112; KRd, n=115; VRd, n=170); no-prior-R was 253 (IRd, n=29; KRd, n=62; VRd, n=162). Overall, R-exposed pts were treated in later LOTs (LOT2: 55% v 78%) and had a longer median time from diagnosis to LOT index (26.7 v 13.4 months) than no-prior-R pts; this varied between cohorts of therapy (TABLE). In R-exposed pts, more pts earned KRd than IRd (75 percent & 23 percent) or VRd (74 percent & 16 percent) with symptomatic relapse (approximately 1 CRAB symptom, 87 percent) or high-risk cytogenetics (30 percent) (TABLE). More IRd-treated pts were ~75 years old: 42% (IRd) v 36% (VRd) / 21% (KRd). 35.3 percent of those receiving VRd in LOT ⇠2 had previous V-IMID-based therapy in R-exposed pts and 53.5 percent had IMID-based therapy in LOT1 (i.e. IMID without PI or monoclonal antibody); >98 percent of LOT1 IMID use was R across categories. 56.5 percent of those receiving KRd had prior V-IMID-based therapy in R-exposed pts and 16.5 percent had IMID-based therapy in LOT1; 29.5 percent and 43.8 percent had prior V-IMID-based and IMID-based therapy in LOT1 in IRd pts in LOT ⇠2. Median TTNT for R-exposed pts: 12.3 months (IRd), 7.8 months (KRd), and 13.9 months (VRd) (P=0.50); median TTNT for TTNTLOT stratified: 0.84 (IRd v KRd), 0.96 (IRd v VRd), 1.15 (KRd v VRd), and median DOT regimen: 8.4 months (IRd), 7.5 months (KRd), and 9.5 months (VRd) (P=0.75) in an unadjusted analysis, at a median f/u of 11, 11.9, and 14.8 months for I-, K-, and V-Rd. HRs for stratified TTNTLOT is important for IRd v KRd (HR=0.33) and KRd v VRd (HR=1.62) (P<0.01, both) at no-prior-R pts; IRd v VRd (HR=0.53; P=0.11). There were no major variations in the modified study for R-exposed pts for TTNT (FIGURE) or DOT regimen PI-Rd regimens. Adjusted HR for TTNT was important for I- v K-Rd (HR=0.36; P=0.03) for no-prior-R pts and significant for I- v V-Rd (HR=0.34; P=0.03) for regimen DOT.
CONCLUSIONS SECTIONS:
In this real-world research, after prior VRd or Rd in the front-line, the majority of pts obtained a PI-Rd combination. The PI-Rd triplets were comparable in TTNT in R-exposed pts treated in LOTs ⇠2 after control for baseline characteristics, including prior PI-exposure. For I-v K-Rd in pts with no-prior-R, TTNT was slightly longer, but this is constrained by small sample sizes. Published studies suggest that individualized therapy recommendations may enhance real-world performance, such as IRd v KRd in fragile pts associated with significantly longer TTNT exposure.6 In our study, prior-R exposure does not appear to affect the relative efficacy of the PI-triplet regimen in LOTs. Understanding real-world care trends and corresponding PI-Rd efficacy in consequent LOTs are crucial to improving RRMM pt management with the growing use of R in earlier LOTs.