THE ROLE OF LENALIDOMIDE MAINTENANCE AND MEASURABLE RESIDUAL DISEASE IN A REAL LIFE MULTIPLE MYELOMA TRANSPLANTED POPULATION RECEIVING DIFFERENT STRATEGIES GUIDED BY ACCESSIBLE TREATMENTS IN BRAZIL

Abstract

Multiple myeloma (MM) treatment and monitoring with MRD-Next Generation Flow (NGF) has evolved fast in the last decade. Nevertheless, its incorporation by low-middle income countries remains challenging. Despite Lenalidomide maintenance (M-Len) after ASCT improves PFS and OS of MM, and MRD-NGF monitoring can discriminate patients with better outcomes, there is no data about these approaches in real-world patients in Brazil (BR) and Latin America. Here we evaluated in two cohorts of patients guided by drug access, the benefit in outcomes of M-Len and MRD-NGF monitoring after ASCT. The study enrolled patients from public and private healthcare systems (HS). A total of 53 patients with symptomatic MM receiving up-front CTD n = 27 or VCD n = 26. All pts had a BM sample at D+100 for MRD-NGF following the EuroFlow SOPs with a limit of detection of 10−6 and a complete protein profile to meet the IMWG response and MRD criteria. Median patient age was 58 (40-70) years, 51% were females. At D+100 the conventional responses were: PR, 5 (9%); VGPR, 21 (40%); CR, 6 (11%); sCR, 21 (40%). Residual plasma-cells were detected by MRD-NGF in 60% of all studied patients and in 44% of those in CR/sCR. MRD+ patients showed a significantly inferior outcome in this setting with median PFS of 26 months vs NR (p = 0.05). Since Len was recently approved in BR and restricted to private HS, we evaluated the impact of this practice in a subset of 18 patients (30%), with a median treatment time of 20.5 months. In this group only, 2/18 (11%) cases progressed whereas in those without maintenance, progression occurred in 19/35 (54%) cases with median PFS NR vs. 21 months (p = 0.001). This benefit also extended to OS, since in the M-len group had no deaths, in contrast to 11/35 (31%) (p = 0.01) deaths in the absence of this drug. Combining the M-Len and MRD-NGF monitoring post ASCT allowed the recognition of groups of patients with different outcomes: M-Len /MRD− (n = 7) vs. no M-Len/MRD+ (n = 21) with medianPFS NR vs 16 months (p = 0.003). Interestingly, the benefit of maintenance was particularly clear among MRD+ these patients had an improved disease control (n = 11) vs MRD+ patients with no M-Len(n = 21): medianPFS NR vs 16 months (p = 0.002) and median OS of NR vs NR (p = 0.02). In our cohort, the majority of patients admitted to the public HS had access to CTD induction without M-Len (n = 24; 45%), while in the private HS they were covered for Bortezomib induction and M-Len post-transplant (n = 15; 28%) with some patients having other mixed situations with VCD induction without M-Len (n = 11; 22%) or CTD+M-Len (n = 3; 5%). Firstly, the comparison between the strategies available by drug access CTD/no-M-len in public vs VCD/M-len in private had an impact on both PFS (median of 16 months vs NR; p = 0.003) and OS (median NR vs NR; p = 0.02). Similarly, patients that had access to PI in induction without M-len also had different outcomes: median PFS NR vs. 21 months for VCD/M-Len vs VCD/no M-Len, respectively (p = 0.01), with a trend in OS (p = 0.06). Finally, different induction regimens (CTD vs VCD without M-Len) showed no impact on PFS (median: 16 vs.21 months; p = 0.6). In real-life, the use of M-Len post-ASCT is associated with better survival outcomes, MRD-NGF was a reproductible and powerful tool to discriminate patients at higher and earlier relapse risk. Inequity of drug access remains a hurdle in countries with constraints, particularly in public HS with a negative impact on survival of MM.