Research Fellow Mayo Clinic rochester, Minnesota, United States
Introduction: Patients (pts) with multiple myeloma (MM) typically receive several different regimens, with the disease eventually becoming refractory to most of the included drugs. For late-line MM refractory to most available therapies, retreatment with a drug that the disease had earlier become refractory to might be one option. In this study we assessed the patterns of care and clinical outcomes of retreatment with previously refractory drugs in pts with MM
Methods: We reviewed 1141 MM pts at our institute who started a new line of therapy for disease progression after January 2015. Of these, 315 pts received a drug that their disease had progressed on previously (index drug) and were included in the study. We collected the duration of initial regimen with index drug and the time gap between last dose of initial regimen and start of retreatment. We then assessed the best response with retreatment according to the IMWG criteria, and progression free survival (PFS) and overall survival (OS) using Kaplan Meier and Cox models
Results: The median age for the cohort was 61 years; 58% pts were male. At diagnosis, 33%, 42%, and 25% pts were International Staging System (ISS) stage I, II, and III; 31% had high risk FISH as per mSMART; median number of prior lines before retreatment was 2 (range 1-12). The index drug was lenalidomide for 45% of pts, bortezomib for 30%, pomalidomide for 11%, and daratumumab for 6% pts. For all pts, the overall response rate (ORR) was 85% (28% ≥VGPR), the median PFS was 11 months (95% CI: 9-13), and the median OS was 53 months (95% CI: 46-66) with retreatment. Of the total 315, 163 (52%) pts were retreated with the index refractory drug in the immediate next line of therapy, and 152 (48%) were retreated with at least 1 intervening line between initial regimen and retreatment. After adjusting for age, ISS stage, high risk FISH, and number of prior lines; pts retreated after 1 or more index drug-free lines had a numerically better PFS (HR=0.7, 95% CI: 0.6-1.1) and OS (HR=0.7, 95% CI: 0.4-1.0) compared to pts retreated in the very next line. After adjusting for above parameters in the subgroup of pts treated after a gap (n=152), pts in quartile (Q) 4 of time gap between last dose of initial regimen and start of retreatment (>34 months) had a better retreatment PFS (HR=0.6, 95% CI: 0.3-1.1) and OS (HR=0.4, 95% CI: 0.2-0.9) as compared to pts in Q1 ( < 8 months gap). HRs (95% CI) for Q2 and Q3 were 1.3 (0.7-2.5) and 1.3 (0.7-2.3) for PFS; and 0.9 (0.5-2.0) and 0.8 (0.4-1.7) for OS.
Conclusions: Retreatment with previously refractory MM drugs might be a viable option, demonstrating an 85% ORR and a 28% ≥VGPR rate in our cohort. Pts retreated with at least 1 intervening line and longer gaps between initial regimen and retreatment had better outcomes than pts retreated in the immediate next line and with shorter index drug-free durations, respectively. These finding highlight the complexity of using refractoriness definitions in defining patient populations for clinical trials.
