P1294: real-world outcomes of 2149 newly diagnosed transplant-eligible multiple myeloma patients

Topic: 22. Stem cell transplantation - Clinical Background: Even though exceedingly effective agents and novel therapeutic strategies are being developed, high-dose chemotherapy followed by autologous stem cell transplantation (HDT/ASCT) has repeatedly proved its importance for fit, newly diagnosed multiple myeloma (NDMM) patients (pts) in prospective clinical trials. Aims: The aim of this study is to provide a comprehensive understanding of HDT/ASCT effectiveness and safety in the real-world heterogenous population of NDMM pts. Methods: We conducted a retrospective, observational study of the Czech Myeloma Group Registry of Monoclonal Gammopathies (RMG). It is a clinical registry established in 2006 that has gathered detailed real-world data in more than 13000 patients who have all signed an informed consent. Only Czech pts who received HDT/ASCT as a part of their initial MM therapy were included. Results: By August 2021, a total of 2149 pts were identified. At the time of MM diagnosis, the median age of the cohort was 59 (42-68) years with 11% (247/2149) of pts over 65 years of age; 45%/31%/24% of pts were ISS stage I/II/III; high-risk cytogenetic features [t(4;14), t(14;16), del(17p)] were found in 33% (243/746) of cases. The combinations of agents used in the induction regimen were proteasome inhibitor (PI), immunomodulatory drug (IMiD) and glucocorticoid (GC) in 29% (631/2149); PI, GC and chemotherapy (CHT) in 24% (525/2149); GC and CHT in 23% (486/2149); IMiD, GC and CHT in 16% (336/2149) and other in 9% (171/2149) of pts. Tandem HDT/ASCT was performed in 12% (268/2149) of cases. Nine percent (198/2149) of pts were treated within a clinical study. After a median follow up of 56 months, mOS and mPFS was 97 (92.8-105.0) and 36 (34.0-37.7) months, respectively. There was a clear improvement in the depth of response (CR+sCR 32% vs. 13%) after HDT/ASCT compared to the post-induction period. Transplant-related mortality (TRM) was equal to 0.7% (16/2141). Age was shown to be a prognostic marker for overall survival – mOS for <50, 51-60, 61-70 and >71year-olds was 135, 101, 88 and 43 months, respectively (p<0.001). The use of HDT/ASCT did not overcome the adverse prognosis of patients with high-risk cytogenetic features – mOS was 101 vs. 61 months (p<0.001) and mPFS was 37 and 25 months (p<0.001) for patients with standard and high cytogenetic risk, respectively. Patients harboring the amplification 1q21 had significantly worse outcome - mOS was 67 vs. 101 months (p<0.001). Whereas translocation (11;14) did not show any influence on survival – mOS 96 vs. 96 months (p=0.784). Patients responding with at least CR after HDT/ASCT achieved significantly better overall survival – mOS was 132, 88 and 90 months for CR+sCR, VGPR, PR and worse, respectively (p<0.001). Our data showed a clinically relevant improvement in PFS when tandem HDT/ASCT was used for patients with high-risk cytogenetics compared to single HDT/ASCT– mPFS 31 vs. 25 months (p=0.132). Summary/Conclusion: RMG is committed to provide robust high-quality real-world data. HDT/ASCT has been a well-established, efficient, and safe procedure and remains a standard of care for first-line treatment. Our analysis of 2149 newly diagnosed transplant-eligible pts confirms high effectiveness (mPFS 36 months) and out-standing safety (TRM 0,7%) of the procedure with long-term survival (mOS 97 months) for eligible NDMM pts. Nevertheless, the concept of tailoring therapy and cellular immunotherapies will undoubtedly bring changes potentially even a revolution in the near future. Keywords: Autologous hematopoietic stem cell transplantation, High risk, Multiple myeloma