Real-World Results of Autologous Stem Cell Transplantation in Newly Diagnosed Patients with Multiple Myeloma: A Multi-Institutional Report from the Canadian Myeloma Research Group (CMRG) Database

INTRODUCTION Autologous stem cell transplant (ASCT) remains an important option for eligible multiple myeloma (MM) patients (pts) as part of initial therapy. In Canada, fit younger pts are typically offered ASCT; selected centers offer tandem ASCT to high-risk (HR) pts; and current standard practice involves continuation of maintenance (maint) therapy until disease progression, which is facilitated by public funding for lenalidomide (len) in this setting. Using our national database, we examined the details and outcomes of ASCT performed as part of initial therapy in eligible Canadian MM pts.

Methods The Canadian Myeloma Research Group database (CMRG-DB) contains both legacy and ongoing prospective data and can track and characterize real-world outcome of pts treated at 17 major Canadian institutions. All pts who received an ASCT as part of initial MM therapy between 01/Jan/2007 to 31/Dec/2021 were included. Progression-free survival (PFS) was calculated from the time of first ASCT until disease progression, death due to any cause or last follow up, whichever comes first, while overall survival (OS) was defined as the time from ASCT to the date of death or last follow up.

Results 3821 pts underwent ASCT as frontline therapy and were included in the analysis. Median age was 61 (range 26-77) years, 15.2% had a creatinine > 177 umol/L and 18% had HR FISH [del17p, t(4;14) and t(14;16)] (FISH was unknown/missing in 50% of pts). The majority (82%) received bortezomib (btz)-based induction; this consisted of CyBorD in 72% with rates of ≥PR (≥VGPR) of 92% (60%). Only 1.6% received a proteasome inhibitor (PI) + len; rates of ≥PR (≥VGPR) were 96.5% (63.2%) in this subgroup. Median time to ASCT from start of induction was 5.6 months (mos). A second induction regimen, including len in 78.5%, was administered to 376 pts for suboptimal response/progression on first induction. The ≥PR (≥VGPR) rates in these 376 pts was 72.9% (35.4%) with a median time from start of second induction to ASCT of 4.2 mos. Tandem ASCT was performed in 314 pts, primarily in HR pts (64%). In HR FISH pts, the median PFS (mPFS) for single vs tandem ASCT was 25.1 vs 35.4 mos (p 0.018) and median OS (mOS) 91.5 vs 84.4 mos (p 0.048), respectively. For those without HR FISH, mPFS and mOS for single vs tandem ASCT were, respectively, 46.5 vs 33.8 mos (p <0.001) and 158.6 vs NYR (p <0.001).

After ASCT, only 205 (5%) pts received consolidation that consisted of a PI + len in 93.2%. However, 2060 pts (53.9%) received post-ASCT maint (len +/- steroids in 63.1%, btz +/- steroids in 2.1 %, len + btz +/- steroids in 1.7%, other PI +/- steroids in 1.6%, len + other PI +/- steroids in 5.7 % and thalidomide +/- steroids in 8.5%).

The mPFS and mOS for all pts was 35.4 mos (95% CI 33.7-37.3) and 125 mos (95% CI 120-138) from first ASCT. Table 1 summarizes the mPFS and mOS according to treatment. Those given a second induction regimen had significantly inferior outcomes (mPFS 27.9 vs 36.2 mos [p 0.001]; mOS 118 vs 126 mos [p 0.011]), although the use of maintenance led to comparable results regardless of number of induction regimens (mPFS 55.3 vs 51.1 mos [p 0.11]; mOS 158.6 vs not yet reached (NYR) [p 0.13]). Consolidation pts had a better mPFS (55.3 vs 34.4 mos [p 0.001]), but no significant gain in mOS (p 0.065). The mPFS and mOS were 48.8 vs 24.5 mos and 159 vs 105 mos for the maint vs non-maint cohorts, respectively, when all types of maint were included. For pts receiving len, btz or both (+/- steroids), the mPFS was 53.7 mos vs 48.2 mos vs 43.5 mos, respectively, while the mOS was 159 mos vs NYR vs 115 mos, respectively. Amongst pts receiving such maint, outcomes for pts with HR FISH were compared with those without HR FISH: mPFS was 36.6 mos vs 55.2 mos and the mOS was 97.4 mos vs 164.4 mos, respectively.

CONCLUSIONS This large study demonstrates that the integration of btz and len into the transplant sequence produces a mOS of ≥10 yrs in most ASCT pts in the real-world setting. Our observations highlight the contribution of post-ASCT maint, particularly len given until progression, when used in multiple pt groups including those with and without HR, as well as those requiring a second induction regimen. Nevertheless, HR pts require additional strategies to optimize results. Further analyses to assess the relationship of pt characteristics, specific treatment details and outcomes are in progress. These results serve as Canadian benchmarks for comparison with newer approaches that combine immunotherapy with ASCT as initial therapy.

Cote:Janssen: Honoraria, Research Funding; Sanofi: Honoraria. Leblanc:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees. McCurdy:BMS: Honoraria, Research Funding; Janssen: Honoraria; Sanofi: Honoraria; GSK: Honoraria; Forus: Honoraria; Amgen: Honoraria; Takeda: Honoraria. Jimenez-Zepeda:Celgene: Honoraria; Janssen: Honoraria; Takeda: Honoraria; Merck: Honoraria; BMS: Honoraria. Song:Amgen: Honoraria; Takeda: Honoraria; Janssen: Honoraria; Celgene: Honoraria, Research Funding. Louzada:Pfizer: Honoraria; Amgen: Honoraria; Celgene: Honoraria; Janssen: Honoraria. Mian:GSK, Janssen, BMS/Celgene, Forus therapeutics, Amgen, Takeda, Sanofi: Honoraria; Janssen: Research Funding. White:Takeda: Honoraria; Sanofi: Honoraria; Karyopharm: Honoraria; BMS: Honoraria; Janssen: Honoraria; Antengene: Honoraria; Forus: Honoraria; GSK: Honoraria; Amgen: Honoraria. Sebag:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite-Gilead: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Stakiw:Janssen: Honoraria; FORUS Therapeutics: Honoraria; BMS: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria; Amgen: Honoraria. Kotb:Akcea: Honoraria; Amgen: Honoraria; BMS: Honoraria; Janssen: Honoraria; Karyopharm: Current equity holder in private company; Merck: Honoraria, Research Funding; Pfizer: Honoraria; Sanofi: Honoraria, Research Funding; Takeda: Honoraria; Celgene: Honoraria. Kaedbey:Janssen, BMS, Sanofi, FORUS, Beigene, Pfizer: Membership on an entity's Board of Directors or advisory committees; BMS. Janssen: Honoraria; Beigene: Other: Advisory boards; FORUS Therapeutics: Other: Advisory boards; Sanofi: Other: Advisory boards; BMS: Honoraria, Other: Advisory boards; Janssen: Honoraria, Other: Advisory boards; Pfizer: Other: Advisory boards; Jewish General Hospital, Montreal, QC, Canada: Current Employment; BMS. Janssen: Honoraria; Janssen, BMS, Sanofi, FORUS, Beigene, Pfizer: Membership on an entity's Board of Directors or advisory committees. Venner:Janssen: Honoraria; Amgen: Honoraria, Research Funding; Takeda: Honoraria; Celgene: Research Funding. Reece:Celgene: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy; Amgen: Consultancy, Honoraria; Millenium: Research Funding; BMS: Research Funding; Merck: Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Sanofi: Honoraria; Otsuka: Research Funding; GSK: Honoraria.