Fraser, Raphael

Background Primary plasma cell leukemia (pPCL) is a rare plasma cell neoplasm with a high mortality rate. There have been improvements in multiple myeloma (MM) outcomes with novel induction agents and use of hematopoietic cell transplantation (HCT) with maintenance, but similar progress has not been reported for pPCL. We examined the outcomes of pPCL patients receiving novel agents with autologous (autoHCT) or allogeneic (alloHCT) approaches as reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) in the modern era. Methods From 2008 to 2015, 348 pPCL pts underwent HCT (N = 277 - autoHCT and 71 - alloHCT) with 45% and 48% having research level data available, respectively. Cumulative incidences of non-relapse mortality (NRM) and relapse/progression (REL), and probability of progression-free survival (PFS) and overall survival (OS) were calculated. Cox multivariate regression was used to model survival after autoHCT only. Median follow-up in autoHCT and alloHCT was 48 and 60 months, respectively. Results AutoHCT Cohort Median age was 60 years and 93% received HCT within 12 months of diagnosis with 76% after a single line of induction (Table 1). 35% had high risk cytogenetics. 23% received bortezomib, doxorubicin, cisplatin, cyclophosphamide, and etoposide (VDPACE). Moreover, 40% received bortezomib (BTZ) and immunomodulatory drug (IMIID)-based triplets. Disease status at HCT was VGPR or better in 47%. 27% received maintenance therapy. At 4 years post-HCT, NRM was 7% (4-11%), REL 76% (69-82%), PFS 17% (13-23%), and OS 28% (22-35%) (Figures 1A, 2A, 2B). Disease status ≥VGPR at HCT and Karnofsky Performance Score >90 significantly predicted superior OS in multivariate analysis. AlloHCT Cohort Median age was 53 years and 89% received HCT within 12 months of diagnosis (Table 1). 61% received a single alloHCT, while 39% used auto-alloHCT tandem approach. 42% had high-risk cytogenetics. 61% received total body irradiation with 44% receiving myeloablative conditioning. Use of VDPACE was higher at 41% in this cohort. VGPR status at HCT was similar (48%), while maintenance was used less often (12%). Grade II-IV acute GVHD occurred in 30% and chronic GVHD in 45%. At four years post-HCT, NRM was 12% (5-21%), REL 69% (56-81%), PFS 19% (10-31%), and OS 31% (19-44%) (Figures 1A, 1B, 2A, 2B). There were no differences in outcomes based on type of HCT. A comparison of post-HCT outcomes of CIBMTR pPCL patients from 1995 to 2006 showed that PFS and OS outcomes are inferior despite lower NRM in this modern cohort (Mahindra et al. Leukemia. 2012). In addition, analysis of SEER (1995-2009) and CIBMTR databases showed that use of HCT increased from 12% (7-21%) in 1995 to 46% (34-64%) in 2009. Conclusion More newly diagnosed pPCL patients are receiving modern induction regimens translating into a higher proportion receiving HCT, but without significant further benefit post-HCT. Post-HCT relapse remains the biggest challenge and further survival in pPCL will likely need a combination of targeted and cell therapy approaches. This study provides a benchmark for future HCT studies for pPCL. Disclosures Girnius: Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genentech: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Dhakal:Takeda: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria. Shah:University of California, San Francisco: Employment; Indapta Therapeutics: Equity Ownership; Genentech, Seattle Genetics, Oncopeptides, Karoypharm, Surface Oncology, Precision biosciences GSK, Nektar, Amgen, Indapta Therapeutics, Sanofi: Membership on an entity's Board of Directors or advisory committees; Celgene, Janssen, Bluebird Bio, Sutro Biopharma: Research Funding; Poseida: Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Nkarta: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite: Consultancy, Membership on an entity's Board of Directors or advisory committees; Teneobio: Consultancy, Membership on an entity's Board of Directors or advisory committees. Qazilbash:Amgen: Consultancy, Other: Advisory Board; Bioclinical: Consultancy; Autolus: Consultancy; Genzyme: Other: Speaker. Kumar:Celgene: Consultancy, Research Funding; Takeda: Research Funding; Janssen: Consultancy, Research Funding. D'Souza:EDO-Mundapharma, Merck, Prothena, Sanofi, TeneoBio: Research Funding; Prothena: Consultancy; Pfizer, Imbrium, Akcea: Membership on an entity's Board of Directors or advisory committees. Hari:BMS: Consultancy, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Amgen: Research Funding; Spectrum: Consultancy, Research Funding; Sanofi: Honoraria, Research Funding; Cell Vault: Equity Ownership; AbbVie: Consultancy, Honoraria.

572 Background: Single-center observational studies have established the use of single or tandem SCT to salvage relapsed GCT but randomized trials are lacking. We analyzed outcomes and prognostic factors in 2,395 male SCT recipients for relapsed GCT between 1990 and 2015. Methods: Recipients of single or tandem SCT reported to the Center for International Blood and Marrow Transplant Research were identified. Outcomes were compared by SCT year: 1990-94 (N = 288), 1995-99 (N = 351), 2000-04 (N = 376), 2005-09 (N = 509) and 2010-15 (N = 871). A recent subset (n = 267, 2000-2015) with detailed disease- and transplant-related data was further analyzed with a multivariate (MVA) Cox proportional hazards model. Results: Median age at SCT was 31 (11-76) years and 49% received SCT within 12 months of diagnosis consistent with early relapse/primary refractory GCT. 26% had primary extragonadal GCT; 1,167 (49%) had intent to tandem transplant (TT). The median follow up was 51 (3-313) months. Day 100 non-relapse mortality was statistically similar at 8% in 1990-94 (vs. 4% in 2010-15) but 3-year progression-free survival (PFS) improved from 24 (18-31)% in 1990-94 to 47 (43-50)% in 2010-15 (p < 0.0001) and 3-year survival (OS) from 35 (29-40)% to 54 (50-57)% in 2010-15 (p < 0.0001). Compared with single SCT, TT recipients were younger 31 (16-62) vs 34 (13-76), with lower Hematopoietic Cell Transplantation-Comorbidity Index, more likely to undergo SCT after 1 line of chemotherapy (28% vs 9%), and within 1 year of diagnosis (51% vs 38%). TT was preferred over single SCT over time (48% of SCT were TT in 2000-04 vs. 81% in 2010-15). In MVA, non-seminoma histology, residual tumor at SCT, receipt of > 1 line of pre-SCT chemotherapy and single SCT (vs. TT), were associated with worse PFS and OS. Year of SCT was not significant when adjusted for these covariates. Conclusions: In this large longitudinal cohort, improvements in PFS and OS were observed in recent years. SCT earlier in disease course and tandem SCT were associated with superior outcomes. These data involving a large cohort reported from 225 centers confirm specialized centers’ date in a real-world setting.