Abstract: Background: Peripheral blood hematopoietic stem cell mobilization for autologous hematopoietic stem cell transplantation (auto-HSCT) in multiple myeloma (MM) can be achieved with either growth factors (GF) alone (filgrastim +/- plerixafor), or with chemotherapy (GF + chemo). When utilized, the chemotherapy regimens include single-agent cyclophosphamide (Cy), or combination regimens, including cyclophosphamide, vincristine or bortezomib, doxorubicin, dexamethasone (CVAD/CBAD) at our center. The optimal mobilization strategy, however, has yet to be established. Methods: In this single center retrospective analysis, we identified 1,006 patients who received auto-HCT for MM between 2009 and 2015. This time-period was chosen to include patients who received auto-HCT after the availability of plerixafor. Patients were divided into 4 groups: G (filgrastim alone), G+P (filgrastim + plerixafor), Cy, and CVAD/CBAD. Plerixafor was mainly used "just-in-time", and not as planned therapy in accordance with our Departmental guidelines. Primary endpoints were CD34+ cell dose/kg collected, days to collect the target CD34+ cell dose, time to neutrophil engraftment (first of three consecutive days of peripheral blood neutrophil count of & gt;500 x 106/L), packed red blood cell (PBRC) and platelet transfusion requirement, duration of hospitalization, progression-free survival (PFS), and overall survival (OS). Results: Patient characteristics are summarized in Table 1. There were 654 patients mobilized with G, 203 with G + P, 80 with Cy, and 69 with CVAD/CBAD. Patients mobilized with CVAD/CBAD were younger compared to the other three groups, were less likely to have achieved VGPR to induction, and more likely to have received a more intense preparative regimen (Table 1). Patients who received G alone, G+P, Cy, and CVAD/CBAD collected a median of 4.1 (0.7-12.2), 4.0 (1.8-11.1), 5.2 (2.2-19.2), and 5.6 (2.5-26.6) x106 CD34+ cells/kg [p & lt;0.001]. Median number of days to collect the target CD34+ cell dose of approximately 6x106 were, 3 (1-10), 5 (1-10), 2 (1-8), and 1 (1-8) for G, G+P, Cy and CVAD/CBAD groups, respectively [p & lt;0.001]. Median time to neutrophil engraftment was 11 days in all four groups, with the range being 8-15, 8-14, 8-13 and 9-13 for G, G+P, Cy and CVAD/CBAD respectively [p=0.021] . Median PRBC units transfused after auto-HCT were 1 (0-13), 1 (0-8), 2 (0-7), and 2 (0-9) for patients in G, G+P, Cy, and CVAD/CBAD groups, respectively [p & lt;0.001]. Median platelets units transfused after auto-HCT were 2 in all four groups. Median duration of hospitalization for auto-HCT was 17 (3-73), 18 (5-84), 18 (4-3 9), and 19 (5-34) days in G, G+P, Cy and CVAD/CBAD groups, respectively [p=0.003]. The 5-year [95% CI] PFS rates were 36.6% [32.9-40.7%], 38.5% [31.5-47%] , 28.9% [20.0-41.5%], and 30.9% [21.5-44.3%] for G, G+P, Cy, and CVAD/CBAD groups, respectively. The 5-year [95% CI] OS rates were 71.3% [67.7-75.1%] , 73.9% [67.3-81.2%], 67.6% [57.3-79.7%] , and 61.7% [51.1-74.5%] for G, G+P, Cy, and CVAD/CBAD groups, respectively. On multivariable analysis, after adjusting for covariates including age, ISS stage, cytogenetic risk, and response to induction, there was no significant impact of mobilization approach on PFS or OS. Conclusion: Approximately 85% of MM patients underwent PBSC mobilization with GF only (G or G+P). GF + chemo (Cy, CVAD/CBAD) was primarily used in patients with suboptimal response to induction, and allowed successful PBSC collection in this high-risk group. GF + chemo-based mobilization was associated with a higher CD34+ cell dose collection, without improving the time to neutrophil or platelet engraftment, PRBC or platelet transfusion requirement, or the duration of hospitalization. Disclosures Bashir: Purdue: Other: Advisory Board; StemLine: Research Funding; Acrotech: Research Funding; Takeda: Other: Advisory Board, Research Funding; Celgene: Research Funding; Amgen: Other: Advisory Board; KITE: Other: Advisory Board. Nieto:Secura Bio: Other: Grant Support; Astra Zeneca: Other: Grant Support; Novartis: Other: Grant Support; Affimed: Consultancy, Other: Grant Support. Hosing:NKARTA Inc.: Consultancy. Popat:Bayer: Research Funding; Novartis: Research Funding. Lee:Sanofi: Consultancy; GlaxoSmithKline: Consultancy, Research Funding; Genentech: Consultancy; Amgen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Genentech: Consultancy; Regeneron: Research Funding; Daiichi Sankyo: Research Funding; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Patel:Bristol Myers Squibb: Consultancy, Research Funding; Oncopeptides: Consultancy; Poseida: Research Funding; Janssen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Cellectis: Research Funding; Precision Biosciences: Research Funding; Takeda: Consultancy, Research Funding; Nektar: Consultancy, Research Funding. Manasanch:Merck: Research Funding; Novartis: Research Funding; Quest Diagnostics: Research Funding; Adaptive Biotechnologies: Honoraria; GSK: Honoraria; Sanofi: Honoraria; BMS: Honoraria; Takeda: Honoraria; JW Pharma: Research Funding; Sanofi: Research Funding. Thomas:BMS: Research Funding; Ascentage: Membership on an entity's Board of Directors or advisory committees, Research Funding; X4 Pharma: Research Funding; Xencor: Research Funding; Pharmacyclics: Other: Advisory Boards; Genentech: Research Funding. Kaufman:Karyopharm: Honoraria; Bristol Myers Squibb: Research Funding; Janssen: Research Funding. Orlowski:Amgen, Inc., AstraZeneca, BMS, Celgene, EcoR1 Capital LLC, Forma Therapeutics, Genzyme, GSK Biologicals, Ionis Pharmaceuticals, Inc., Janssen Biotech, Juno Therapeutics, Kite Pharma, Legend Biotech USA, Molecular Partners, Regeneron Pharmaceuticals, Inc.,: Honoraria, Membership on an entity's Board of Directors or advisory committees; Laboratory research funding from BioTheryX, and clinical research funding from CARsgen Therapeutics, Celgene, Exelixis, Janssen Biotech, Sanofi-Aventis, Takeda Pharmaceuticals North America, Inc.: Research Funding; Founder of Asylia Therapeutics, Inc., with associated patents and an equity interest, though this technology does not bear on the current submission.: Current equity holder in private company, Patents & Royalties; Sanofi-Aventis, Servier, Takeda Pharmaceuticals North America, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees; STATinMED Research: Consultancy. Champlin:Actinium: Consultancy; Johnson and Johnson: Consultancy; Omeros: Consultancy; Cytonus: Consultancy; DKMS America: Membership on an entity's Board of Directors or advisory committees; Genzyme: Speakers Bureau; Takeda: Patents & Royalties. Qazilbash:Bioclinica: Consultancy; Amgen: Research Funding; Janssen: Research Funding; Angiocrine: Research Funding; Bioline: Research Funding.

Abstract: Background: Hematopoietic cell transplantation (HCT) is an integral part of the treatment of multiple myeloma (MM). While autologous stem cell transplantation (auto-HCT) is most commonly used, the duration of response is typically finite. Allogeneic HCT (allo-HCT) can provide prolonged survival in some patients, given the added benefit of the graft-versus-myeloma effect. However, long-term data is needed to show this improvement. Method: We retrospectively reviewed a cohort of 37 consecutive patients with newly diagnosed MM who received allo-HCT as part of consolidation therapy between 1994 to 2016. Results: The median age was 54 years (range, 32 to 68), and 54% were male. The Revised International Staging System (R-ISS) stages were I, II, III, and unknown in 27%, 38%, 11%, and 24% of patients, respectively. High-risk cytogenetics (IMWG definition) was identified in 22% of patients. The median time from diagnosis to allo-HCT was 8.8 months (range; 3.3 to 34.3). For induction treatment, fourteen patients (38%) received a combination of immunomodulatory drug (IMiD) plus proteasome inhibitor (PI), sixteen patients (43%) received either IMiD or PI in combination with other agents, and seven patients (19%) did not receive either an IMiD or PI. Twenty-seven (73%) patients received auto-HCT before allo-HCT. Thirty-four (92%) patients received allo-HCT as part of various clinical trials. Median time from auto-HCT to allo-HCT was 4 months (2.5 to 27.3). Prior to allo-HCT, 1 (3%) patient was in complete remission (CR), 18 (48.5%) were in very good partial remission (VGPR), and 18 (48.5%) were in partial remission (PR). Twenty-three (62%) patients received non-myeloablative (NMA) conditioning, 10 (27%) reduced-intensity (RIC), and 4 (11%) myeloablative conditioning (MAC). The graft source was matched unrelated (MUD) in 16% and matched sibling donor (MRD) in 84% of patients. Ten (27%) patients received maintenance therapy after allo-HCT, including bortezomib (n=2), thalidomide (n=2), ixazomib (n=2), and lenalidomide (n=4). The median days to neutrophil and platelet engraftment was 12 (ANC ≥500/µL_ range; 10 to 59) and 13 (platelet count ≥20K/µL _range; 9 to 70), respectively. The cumulative incidence (CI) of non-relapse mortality (NRM) was 16% at 1-year and 19% at 3-years after allo-HCT. There was no difference in NRM between MAC or NMA/RIC conditioning. The overall response rate (PR or better) was 97%, with a 54% stringent CR+CR rate. The incidence of grade I-IV acute graft-versus-host disease (GVHD) was 35%, while chronic GVHD was seen in 62%. Causes of death were deemed to be disease-related in 8 patients, treatment-related in 11 patients, and 1 unknown. The median follow-up in surviving patients was 12.6 years (range; 2.8 to 15.8 years). The 3, 5, and 10-year actuarial overall survival (OS) rates were 70%, 56%, and 47%, respectively (Figure 1A). The 3, 5, and 10-year actuarial progression-free survival (PFS) rates were 66%, 50%, and 36%, respectively (Figure 1B). At the last follow up, 46% (n=17) of patients were alive in the entire cohort, 65% (n=11) of which survived for longer than 10-years from transplant. Sixteen percent (n=6) remained alive and in continued remission for more than 10 years from transplant, one-third of whom received maintenance treatment post allo-HCT. The longest ongoing remission was 15.8 years in this cohort. Conclusion: Allo-HCT may result in durable ( & gt;10 years) remission in a number of MM patients when performed early in the disease course. Larger studies would help identify the patients who would benefit the most, given the risk of graft-versus-host disease after allo-HCT. Disclosures Popat: Bayer: Research Funding; Novartis: Research Funding. Kebriaei:Pfizer: Other: Served on advisory board; Kite: Other: Served on advisory board; Amgen: Other: Research Support; Jazz: Consultancy; Novartis: Other: Served on advisory board; Ziopharm: Other: Research Support. Oran:Celgene: Consultancy; ASTEX: Research Funding; Arog Pharmaceuticals: Research Funding. Hosing:NKARTA Inc.: Consultancy. Manasanch:Adaptive Biotechnologies: Honoraria; GSK: Honoraria; Sanofi: Honoraria; BMS: Honoraria; Takeda: Honoraria; Quest Diagnostics: Research Funding; Merck: Research Funding; JW Pharma: Research Funding; Novartis: Research Funding; Sanofi: Research Funding. Lee:Amgen: Consultancy, Research Funding; Genentech: Consultancy; Regeneron: Research Funding; Daiichi Sankyo: Research Funding; Sanofi: Consultancy; GlaxoSmithKline: Consultancy, Research Funding; Genentech: Consultancy; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding. Kaufman:Karyopharm: Honoraria; Bristol Myers Squibb: Research Funding; Janssen: Research Funding. Patel:Precision Biosciences: Research Funding; Takeda: Consultancy, Research Funding; Cellectis: Research Funding; Janssen: Consultancy, Research Funding; Poseida: Research Funding; Oncopeptides: Consultancy; Nektar: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding. Orlowski:Founder of Asylia Therapeutics, Inc., with associated patents and an equity interest, though this technology does not bear on the current submission.: Current equity holder in private company, Patents & Royalties; STATinMED Research: Consultancy; Sanofi-Aventis, Servier, Takeda Pharmaceuticals North America, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Laboratory research funding from BioTheryX, and clinical research funding from CARsgen Therapeutics, Celgene, Exelixis, Janssen Biotech, Sanofi-Aventis, Takeda Pharmaceuticals North America, Inc.: Research Funding; Amgen, Inc., AstraZeneca, BMS, Celgene, EcoR1 Capital LLC, Forma Therapeutics, Genzyme, GSK Biologicals, Ionis Pharmaceuticals, Inc., Janssen Biotech, Juno Therapeutics, Kite Pharma, Legend Biotech USA, Molecular Partners, Regeneron Pharmaceuticals, Inc.,: Honoraria, Membership on an entity's Board of Directors or advisory committees. Thomas:Ascentage: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; X4 Pharma: Research Funding; Pharmacyclics: Other: Advisory Boards; Xencor: Research Funding; Genentech: Research Funding. Shpall:Takeda: Other: Licensing Agreement; Magenta: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Adaptimmune: Membership on an entity's Board of Directors or advisory committees; Zelluna: Membership on an entity's Board of Directors or advisory committees. Champlin:Takeda: Patents & Royalties; Actinium: Consultancy; Johnson and Johnson: Consultancy; Omeros: Consultancy; Cytonus: Consultancy; DKMS America: Membership on an entity's Board of Directors or advisory committees; Genzyme: Speakers Bureau. Qazilbash:Bioclinica: Consultancy; Amgen: Research Funding; Angiocrine: Research Funding; Bioline: Research Funding; Janssen: Research Funding. Bashir:Celgene: Research Funding; Amgen: Other: Advisory Board; Purdue: Other: Advisory Board; Takeda: Other: Advisory Board, Research Funding; Acrotech: Research Funding; StemLine: Research Funding; KITE: Other: Advisory Board.

Abstract: Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.

Abstract: Background: There has been an increased use of novel agents in the induction therapy for transplant-eligible AL amyloidosis over past decade. Hematologic response after an autologous hematopoietic stem cell transplantation (ASCT) is predictive of better outcomes, including organ response and overall survival. However, limited data exist about the outcomes of patients who are refractory to induction chemotherapy but proceed with upfront ASCT). We present here the outcomes of AL amyloidosis refractory to induction therapy. Methods: This retrospective study included all consecutive AL patients who had their ASCT at our institution between 01/2008 and 12/2018 and received induction therapy. We excluded patients who were untreated at the time of transplant. Primary objective: assess the hematologic response, progression-free survival (PFS) and overall survival (OS). Secondary objective: compare PFS and OS of AL amyloidosis by response to induction therapy (refractory vs sensitive). Refractory disease was defined as patient who had stable disease (SD) or progressive disease (PD) after at least 1 line of induction therapy. Hematologic response was defined per the 2012 consensus criteria. Survival estimates were calculated using Kaplan-Meier method. Results: One-hundred-and-eleven patients with a median age of 61 (range, 27-77) years met eligibility criteria. Thirty-three (30%) were refractory and 78 (70%) were sensitive to induction therapy. Table 1 summarizes patient and disease characteristics of all study patients and for the refractory vs sensitive groups. Overall, the two groups were comparable except for significantly more kidney involvement in the refractory group (97% of patients). Induction therapies were similar in the two groups, with bortezomib/cyclophosphamide/dexamethasone (VCD) being the most commonly used regimen (46%). With a median follow-up of 3.11 (range, 0.18-11.15) years, the 3-year PFS and OS for all study patients were 67% and 78%, respectively. At 3 months after transplant, 74% of the patients in the refractory group achieved an objective hematologic response (OHR; defined as PR or better). Of these, 29% achieved VGPR/CR and 45% achieved PR. As expected, more patients in the sensitive group achieved OHR (97%) and VGPR/CR (76%). The respective 3-year PFS and OS were 49% and 73% in the refractory group compared to 75% and 83% in the sensitive group (p=0.0068 for PFS; p=0.0790 for OS). Univariate analysis (UVA) was performed for the variables listed in Table 1 and multivariable analyses included only factors with p value & lt;0.1 in in the UVA. In MVA, in addition to increased risk for refractory patients (HR 2.885, 95% CI:1.237-6.729; p=0.0142), only elevated beta-2 microglobulin (HR 3.899, 95% CI:1.039-14.629; p=0.0437) was associated with inferior PFS. Regarding OS, age ≥60 (HR 3.812, 95% CI:1.038-14.002; p=0.0438) and revised Mayo stage III/IV (HR 3.886, 95% CI: 1.029-14.679; p=0.0453) were associated with inferior survival. In a subgroup analysis comparing PFS and OS stratifying patients by their response to induction (refractory vs sensitive) and their 3-month hematologic response after transplant, we found no significant differences in the 3-year PFS (86% for refractory vs 80% for sensitive group; p=0.7284) for those with VGPR or better but significantly inferior PFS for refractory patients who achieved & lt;VGPR (27% compared to 74% for the sensitive group; p=0.0196). Conclusion: AL amyloid patients refractory to induction therapy seem to benefit from high-dose chemotherapy and ASCT in terms of both response rates and survival. Durable responses for refractory disease are notable in patients who achieved & gt;VGPR after ASCT. Prospective studies comparing transplant versus non-transplant approaches are warranted for these high-risk patients. Figure 1 Figure 1. Disclosures Hosing: Nkarta Therapeutics: Membership on an entity's Board of Directors or advisory committees. Popat: Bayer: Research Funding; Abbvie: Research Funding; Novartis: Research Funding; Incyte: Research Funding. Lee: Bristol Myers Squibb: Consultancy; Celgene: Consultancy; Genentech: Consultancy; Janssen: Consultancy, Research Funding; Karyopharm: Consultancy; Legend Biotech: Consultancy; GlaxoSmithKline: Consultancy, Research Funding; Sanofi: Consultancy; Oncopetides: Consultancy; Takeda Pharmaceuticals: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Regeneron: Research Funding. Orlowski: Asylia Therapeutics, Inc., BioTheryX, Inc., and Heidelberg Pharma, AG.: Other: Laboratory research funding; Asylia Therapeutics, Inc.: Current holder of individual stocks in a privately-held company, Patents & Royalties; Amgen, Inc., BioTheryX, Inc., Bristol-Myers Squibb, Celgene, Forma Therapeutics, Genzyme, GSK Biologicals, Janssen Biotech, Juno Therapeutics, Karyopharm Therapeutics, Inc., Kite Pharma, Neoleukin Corporation, Oncopeptides AB, Regeneron Pharmaceuticals, I: Membership on an entity's Board of Directors or advisory committees; CARsgen Therapeutics, Celgene, Exelixis, Janssen Biotech, Sanofi-Aventis, Takeda Pharmaceuticals North America, Inc.: Other: Clinical research funding; Amgen, Inc., BioTheryX, Inc., Bristol-Myers Squibb, Celgene, EcoR1 Capital LLC, Genzyme, GSK Biologicals, Janssen Biotech, Karyopharm Therapeutics, Inc., Neoleukin Corporation, Oncopeptides AB, Regeneron Pharmaceuticals, Inc., Sanofi-Aventis, and Takeda P: Consultancy, Honoraria. Qazilbash: Janssen: Research Funding; Biolline: Research Funding; Angiocrine: Research Funding; Amgen: Research Funding; NexImmune: Research Funding; Bristol-Myers Squibb: Other: Advisory Board; Oncopeptides: Other: Advisory Board.

Abstract: Introduction: Multiple myeloma (MM) remains incurable with only a small proportion of patients surviving over 10 years (long-term survivors) from diagnosis. It has been more than 3 decades since the first autologous stem cell transplantation (ASCT) was performed for MM at our institution. In this study, we sought to determine baseline patient and disease characteristics that are associated with long-term survival after the ASCT. Methods: We included all consecutive patients who received their first ASCT between January 1988 and December 2015. The primary objective was to identify the variables associated with long-term overall survival ( & gt;10 years). The control group were patients who survived less than 10 years from their diagnosis data (short-term survivors). Logistic regression models were used to evaluate the association between predictive factors and overall survival of & gt; 10 years. Results: Among 2176 patients who underwent their first ASCT during the study period, 1409 patients met the eligibility criteria. Overall, 392 (28%) patients were long-term survivors ( & gt;10 years) and 1017 (72%) were short-term survivors ( & lt;10 years). Table 1 shows baseline patient and disease characteristics. Only 24% and 42% of patients in the long-term and short-term survivor groups, respectively, received proteasome inhibitor-based induction therapies. Maintenance therapy was received by 49% and 45% in the short- and long-term survivor groups, respectively (p=0.19). The long-term survivor group was characterized by having higher percentage of patients younger than age 65 (86%) years, and having higher proportions of ISS Stage I (47%), standard-risk cytogenetics (96%), normal LDH (88%) and with serum creatinine & lt;2 mg/d (87%). With a median follow-up of 13 years (range, 10-30 years), the 15-year PFS and OS survival rates in the long-term survivors were 19% (95% CI: 14% - 23%) and 62% (95%: CI 56% - 68%) (Figure 1A). The cumulative incidence rates of relapse at 1, 3, and 5 years in the short-term survival group were 9%, 63%, and 82%, respectively, compared to 2%, 20%, and 40%, respectively, in the long-term survivor group (p & lt;0.001) (Figure 1B). All variables listed in Table 1 were assessed in univariate analysis. Seventy-six percent of patients were relapse-free at 24 months in the long-term survival group, compared to only 32% in the short-term survival group. On multivariable analysis, age, cytogenetic-risk status, race-ethnicity, and duration of remission after ASCT were significant predictors for surviving & gt; 10 years (Table 2). ISS Stage III (vs. Stage I: OR 0.45, 95% CI 0.19-1.09; p=0.08) showed a trend towards surviving ≤ 10 years. Conclusions: ASCT is associated with durable responses and prolonged survival in a subgroup of MM patients irrespective of type of induction therapy and/or use of maintenance therapy. Duration of remission after transplant is the strongest predictor for long-term survival. Age & lt;65 years, being African-American, and standard-risk cytogenetics were also associated with surviving more than 10 years. Disclosures Bashir: Acrotech: Research Funding; StemLine: Research Funding; Celgene: Research Funding; Amgen: Other: Advisory Board; Purdue: Other: Advisory Board; Takeda: Other: Advisory Board, Research Funding; KITE: Other: Advisory Board. Nieto:Affimed: Consultancy, Other: Grant Support; Novartis: Other: Grant Support; Astra Zeneca: Other: Grant Support; Secura Bio: Other: Grant Support. Mehta:CSL Behring: Research Funding; Incyte: Research Funding; Kadmon: Research Funding. Ciurea:Kiadis Pharma: Current equity holder in publicly-traded company, Research Funding. Popat:Bayer: Research Funding; Novartis: Research Funding. Khouri:Bristol Myers Squibb: Research Funding; Pfizer: Research Funding. Kebriaei:Ziopharm: Other: Research Support; Novartis: Other: Served on advisory board; Pfizer: Other: Served on advisory board; Jazz: Consultancy; Kite: Other: Served on advisory board; Amgen: Other: Research Support. Manasanch:GSK: Honoraria; Adaptive Biotechnologies: Honoraria; Merck: Research Funding; Quest Diagnostics: Research Funding; Takeda: Honoraria; BMS: Honoraria; Sanofi: Research Funding; Novartis: Research Funding; Sanofi: Honoraria; JW Pharma: Research Funding. Hosing:NKARTA Inc.: Consultancy. Patel:Janssen: Consultancy, Research Funding; Nektar: Consultancy, Research Funding; Cellectis: Research Funding; Poseida: Research Funding; Oncopeptides: Consultancy; Precision Biosciences: Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Takeda: Consultancy, Research Funding. Lee:Regeneron: Research Funding; Amgen: Consultancy, Research Funding; Genentech: Consultancy; Sanofi: Consultancy; Janssen: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Genentech: Consultancy; Daiichi Sankyo: Research Funding; Celgene: Consultancy, Research Funding; GlaxoSmithKline: Consultancy, Research Funding. Shpall:Zelluna: Membership on an entity's Board of Directors or advisory committees; Takeda: Other: Licensing Agreement; Adaptimmune: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Magenta: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Orlowski:Laboratory research funding from BioTheryX, and clinical research funding from CARsgen Therapeutics, Celgene, Exelixis, Janssen Biotech, Sanofi-Aventis, Takeda Pharmaceuticals North America, Inc.: Research Funding; Founder of Asylia Therapeutics, Inc., with associated patents and an equity interest, though this technology does not bear on the current submission.: Current equity holder in private company, Patents & Royalties; STATinMED Research: Consultancy; Sanofi-Aventis, Servier, Takeda Pharmaceuticals North America, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen, Inc., AstraZeneca, BMS, Celgene, EcoR1 Capital LLC, Forma Therapeutics, Genzyme, GSK Biologicals, Ionis Pharmaceuticals, Inc., Janssen Biotech, Juno Therapeutics, Kite Pharma, Legend Biotech USA, Molecular Partners, Regeneron Pharmaceuticals, Inc.,: Honoraria, Membership on an entity's Board of Directors or advisory committees. Champlin:Omeros: Consultancy; Cytonus: Consultancy; Johnson and Johnson: Consultancy; Actinium: Consultancy; Genzyme: Speakers Bureau; Takeda: Patents & Royalties; DKMS America: Membership on an entity's Board of Directors or advisory committees. Qazilbash:Bioclinica: Consultancy; Amgen: Research Funding; Janssen: Research Funding; Angiocrine: Research Funding; Bioline: Research Funding.

Abstract: Background: Risk stratification for Immunoglobulin light chain amyloidosis (AL) has been refined with advances in the understanding of disease biology. Although nonspecific, beta 2 microglobulin (β2M) levels correlate with disease burden and are considered a prognostic marker in several hematologic malignancies. Recently, we and others have shown the association of β2M levels with survival in AL. In this study, we evaluated the role of β2M as a predictor of outcome for high-dose chemotherapy and autologous hematopoietic stem cell transplantation (auto-HCT) in patients with AL. Methods: We identified 175 consecutive patients with AL who received auto-HCT between 2009 and 2019 at our institution. A β2M≥3.5 mg/L, regardless of renal function status was used as a cutoff value. Hematologic and organ responses were evaluated according to the Consensus Guidelines for AL. Revised Mayo staging system was utilized for Cardiac staging. Results: The median age at auto-HCT was 60 years (range, 27 to 77). Of 175 patients, 153 (87%) had a β2M value available, of whom 57 (37%) had a β2M ≥ 3.5 mg/L. There were no significant differences in baseline characteristics between the 2 groups, except for the higher level of LDH, worse renal function, and more patients with renal involvement in the β2M ≥ 3.5 group, and more patients with lambda light chain type in the β2M & lt;3.5 group (Table 1). The median follow-up from auto-HCT was 38 months (range; 1 to 124). One-year non-relapse mortality (NRM) was 2%. The 1-year NRM was 5% (n=3) and 1% (n=1) in patients with β2M≥3.5, and β2M & lt;3.5, respectively (p=0.115). Hematologic CR after auto-HCT was seen in 21 (37%), and 38 (40%) patients with β2M≥3.5 and β2M & lt;3.5, respectively (p=0.864). Organ response (OR) after auto-HCT was seen in 36 (73%), and 65 (71%) patients with β2M≥3.5 and β2M & lt;3.5, respectively (p=1.00). The 3-year progression-free survival (PFS) was 66%, and 74% in patients with β2M≥3.5, and β2M & lt;3.5 (p=0.17) (Figure 1A).The 3-year overall survival (OS) was 73%, ad 89% in patients with β2M≥3.5, and β2M & lt;3.5 (p=0.009) (Figure 1B). On Cox-regression multivariate analysis, cardiac involvement with AL (p=0.043), and β2M≥3.5 (p=0.029) were associated with a shorter OS. Conclusion: In this single-center retrospective analysis, we showed that high serum β2M is associated with shorter OS. β2M may be incorporated as a prognostic marker for AL if these findings are confirmed in larger studies. Disclosures Bashir: Acrotech: Research Funding; StemLine: Research Funding; Celgene: Research Funding; Takeda: Other: Advisory Board, Research Funding; KITE: Other: Advisory Board; Amgen: Other: Advisory Board; Purdue: Other: Advisory Board. Hosing:NKARTA Inc.: Consultancy. Popat:Bayer: Research Funding; Novartis: Research Funding. Kebriaei:Novartis: Other: Served on advisory board; Jazz: Consultancy; Ziopharm: Other: Research Support; Kite: Other: Served on advisory board; Pfizer: Other: Served on advisory board; Amgen: Other: Research Support. Shpall:Takeda: Other: Licensing Agreement; Magenta: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Adaptimmune: Membership on an entity's Board of Directors or advisory committees; Zelluna: Membership on an entity's Board of Directors or advisory committees. Manasanch:Sanofi: Research Funding; Adaptive Biotechnologies: Honoraria; GSK: Honoraria; Sanofi: Honoraria; BMS: Honoraria; Takeda: Honoraria; Quest Diagnostics: Research Funding; Merck: Research Funding; JW Pharma: Research Funding; Novartis: Research Funding. Lee:Amgen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Daiichi Sankyo: Research Funding; Regeneron: Research Funding; Genentech: Consultancy; Janssen: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Sanofi: Consultancy; GlaxoSmithKline: Consultancy, Research Funding; Genentech: Consultancy. Kaufman:Janssen: Research Funding; Karyopharm: Honoraria; Bristol Myers Squibb: Research Funding. Patel:Cellectis: Research Funding; Nektar: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Precision Biosciences: Research Funding; Oncopeptides: Consultancy; Poseida: Research Funding. Thomas:BMS: Research Funding; Ascentage: Membership on an entity's Board of Directors or advisory committees, Research Funding; X4 Pharma: Research Funding; Genentech: Research Funding; Xencor: Research Funding; Pharmacyclics: Other: Advisory Boards. Orlowski:STATinMED Research: Consultancy; Founder of Asylia Therapeutics, Inc., with associated patents and an equity interest, though this technology does not bear on the current submission.: Current equity holder in private company, Patents & Royalties; Sanofi-Aventis, Servier, Takeda Pharmaceuticals North America, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen, Inc., AstraZeneca, BMS, Celgene, EcoR1 Capital LLC, Forma Therapeutics, Genzyme, GSK Biologicals, Ionis Pharmaceuticals, Inc., Janssen Biotech, Juno Therapeutics, Kite Pharma, Legend Biotech USA, Molecular Partners, Regeneron Pharmaceuticals, Inc.,: Honoraria, Membership on an entity's Board of Directors or advisory committees; Laboratory research funding from BioTheryX, and clinical research funding from CARsgen Therapeutics, Celgene, Exelixis, Janssen Biotech, Sanofi-Aventis, Takeda Pharmaceuticals North America, Inc.: Research Funding. Champlin:Genzyme: Speakers Bureau; Johnson and Johnson: Consultancy; Actinium: Consultancy; Cytonus: Consultancy; Omeros: Consultancy; DKMS America: Membership on an entity's Board of Directors or advisory committees; Takeda: Patents & Royalties. Qazilbash:Angiocrine: Research Funding; Bioline: Research Funding; Amgen: Research Funding; Bioclinica: Consultancy; Janssen: Research Funding.

Abstract: Background: Since the introduction of novel anti-myeloma agents, multiple studies have shown disparate survival outcomes among African American (AA) patients compared to whites with multiple myeloma (MM). Limited access to novel therapies and autologous hematopoietic stem cell transplant (auto-HCT) has been considered partly responsible for the lower survival outcomes in AA, but other disease-related features may also contribute to this disparity. We hypothesize that patients receiving ASCT would have equal healthcare access, which may nullify the impact of disparate access to novel drugs and healthcare facilities. To test this hypothesis, we compared survival outcomes of AA and whites with MM who underwent upfront ASCT at our center through propensity score matching analysis. Methods and patients: A total of 705 MM patients, including AA and whites, who underwent auto-HCT at our institution from 2007 to 2015. By using 1:1 propensity-matching, we identified 251 patients, 125 AA and 126 whites. Clinical response, relapse, and progression were defined by the International Myeloma Working Group criteria. Results: Table 1 includes the baseline characteristics of the matched doublets. Patients in the two groups were well matched for age at auto-HCT, ISS stage, serum creatinine, induction, response to induction, consolidation, preparative regimen, and maintenance therapy. The median follow-up for the matched cohort was 71.5 (interquartile range: 51.6-90.3) months. The overall response rate (CR+VGPR+PR) after auto-HCT was 95.2% (119/125 patients)) and 98.4% (123/125 patients) in the AA and the white group, respectively (p = 0.289). Thirty-four (27.2%) patients achieved a CR in each group. Sixty (48.0%) and 62 (49.6%) patients achieved a VGPR in the AA and the white group, respectively. The median PFS for the AA and the white group was 44.6 (95%CI: 35.5 - 54.7) and 51.0 (95%CI: 38.3 - 63.9) months, respectively (p = 0.763, stratified log-rank test). The 4-year PFS in the AA and the white group was 48% (95%CI: 39.3 - 57.8) and 51.2% (95%CI: 43.0 - 61.0), respectively (Fig. 1). The 4-year OS in the AA and the white group was 78.5% (95%CI: 71.5 - 86.2) and 80.9% (95%CI: 74.1 - 88.2), respectively (Fig. 2). Conclusions: In this propensity score matching analysis of MM patients who underwent an auto-HCT at our institution, we showed that AA patients had similar response rates, PFS, and OS as white patients Disclosures Bashir: KITE: Other: Advisory Board; Amgen: Other: Advisory Board; Purdue: Other: Advisory Board; Celgene: Research Funding; StemLine: Research Funding; Takeda: Other: Advisory Board, Research Funding; Acrotech: Research Funding. Popat:Bayer: Research Funding; Novartis: Research Funding. Hosing:NKARTA Inc.: Consultancy. Nieto:Secura Bio: Other: Grant Support; Affimed: Consultancy, Other: Grant Support; Astra Zeneca: Other: Grant Support; Novartis: Other: Grant Support. Kebriaei:Amgen: Other: Research Support; Ziopharm: Other: Research Support; Novartis: Other: Served on advisory board; Jazz: Consultancy; Kite: Other: Served on advisory board; Pfizer: Other: Served on advisory board. Alousi:Incyte: Honoraria, Research Funding; Therakos: Research Funding; Alexion: Honoraria. Mehta:Kadmon: Research Funding; Incyte: Research Funding; CSL Behring: Research Funding. Khouri:Bristol Myers Squibb: Research Funding; Pfizer: Research Funding. Thomas:Genentech: Research Funding; BMS: Research Funding; Ascentage: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Other: Advisory Boards; X4 Pharma: Research Funding; Xencor: Research Funding. Lee:Janssen: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Genentech: Consultancy; GlaxoSmithKline: Consultancy, Research Funding; Sanofi: Consultancy; Regeneron: Research Funding; Daiichi Sankyo: Research Funding; Genentech: Consultancy; Amgen: Consultancy, Research Funding. Patel:Janssen: Consultancy, Research Funding; Oncopeptides: Consultancy; Nektar: Consultancy, Research Funding; Precision Biosciences: Research Funding; Takeda: Consultancy, Research Funding; Cellectis: Research Funding; Celgene: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Poseida: Research Funding. Orlowski:Sanofi-Aventis, Servier, Takeda Pharmaceuticals North America, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Founder of Asylia Therapeutics, Inc., with associated patents and an equity interest, though this technology does not bear on the current submission.: Current equity holder in private company, Patents & Royalties; Amgen, Inc., AstraZeneca, BMS, Celgene, EcoR1 Capital LLC, Forma Therapeutics, Genzyme, GSK Biologicals, Ionis Pharmaceuticals, Inc., Janssen Biotech, Juno Therapeutics, Kite Pharma, Legend Biotech USA, Molecular Partners, Regeneron Pharmaceuticals, Inc.,: Honoraria, Membership on an entity's Board of Directors or advisory committees; Laboratory research funding from BioTheryX, and clinical research funding from CARsgen Therapeutics, Celgene, Exelixis, Janssen Biotech, Sanofi-Aventis, Takeda Pharmaceuticals North America, Inc.: Research Funding; STATinMED Research: Consultancy. Champlin:Actinium: Consultancy; Johnson and Johnson: Consultancy; Cytonus: Consultancy; Omeros: Consultancy; Genzyme: Speakers Bureau; DKMS America: Membership on an entity's Board of Directors or advisory committees; Takeda: Patents & Royalties. Qazilbash:Bioclinica: Consultancy; Angiocrine: Research Funding; Amgen: Research Funding; Bioline: Research Funding; Janssen: Research Funding.

Abstract: Introduction The role of upfront autologous stem cell transplantation (ASCT) for multiple myeloma (MM) has evolved over the last three decades, with significant improvements in preparative regimen, supportive care, induction, and maintenance therapy. In this study, we evaluated the survival trends for MM after ASCT in the last 25-years. Methods We included all consecutive MM patients who underwent their first ASCT at our center between January 1990 and December 2015. The primary aim was to compare survival trends at different time points. Secondary aims were to evaluate the impact of age ( & lt;65 vs ≥ 65 years), cytogenetics (standard vs high), and ISS stage (I vs II vs III) on survival. Primary endpoints were 5-year overall survival (OS) and progression-free survival (PFS). Secondary endpoints were cumulative incidence of relapse (CIR) and non-relapse mortality (NRM). The Kaplan-Meier method was used to estimate OS and PFS. CIR and NRM were determined using the competing risks method. Results Overall, 2171 patients received their first ASCT during the study period. Median age was 58.5 (range: 23 - 82) years, 59% were males. Patients were subgrouped into 5 study periods, based on the years new therapies were approved and/or introduced in each period [specifically, the introduction of immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs)]: 1990-2001 (n=329; predominantly conventional induction chemotherapy), 2002-2005 (n=349; IMiD or conventional chemotherapy), 2006-2008 (n=341; IMiD or PI), 2009-2011 (n=429; predominantly PI over IMiD), and 2012-2015 (n=723; predominantly triplet therapy IMiD+PI, and majority received maintenance therapy). Compared to the 1990-2001 cohort (median age 52, range 22-71; 10% had ≥VGPR at ASCT), patients in the 2012-2015 cohort were older (median age 61, range 25-82) and had a deeper response at ASCT (≥VGPR: 49%). With a median follow up of 60.4 (0.2 - 302) months, the median PFS and OS and for all study patients were 32.4 and 89.5 months, respectively. There were significant improvements in PFS (HR [95%CI] 0.85 [0.83-0.88]; p & lt;0.001) and OS (0.86 [0.83, 0.90]; p & lt;0.001) trends over the study period. Median [95% CI] PFS and 5-year PFS improved from 1.8 [1.5-2.1] years and 21% in the 1990-2001 cohort, to 3.7 [3.3-4.1] years and 40%, respectively, in 2012-2015 (Figure 1A). Similarly, median [95% CI] OS and 5-year OS increased from 4.7 [3.9-5.6] years and 47%, respectively, in the 1990-2001 cohort, to not reached (NR) [7.0 years - NR] and 73%, respectively in the 2012-2015 cohort (Figure 1B). CIR improved with each subsequent study period, with 5-year rates of 68% in 1990-2001 and 56% in 2012-2015 (HR 0.88 [0.85-0.91]; p & lt;0.001). Furthermore, a significant improvement in NRM was also noted, with decrease in 3-year NRM from 10% in 1990-2001 to 2% in 2012-2015 (HR 0.77 [0.69-0.87]; p & lt;0.001). In univariate analysis, significant improvements in PFS and CIR were noted across all patient subgroups with each subsequent study period. However, regarding the OS benefit, there was no significant improvements for age ≥ 65 years (HR 0.93 [0.82-1.05]; p=0.23) and ISS stage III (HR 0.94 [0.86-1.03] ; p=0.18) subgroups. Patients with poor-risk cytogenetics had significant improvement, albeit remained with inferior outcomes relative to other subgroups; 5-year PFS and OS of 32% and 58% in 2012-2015, respectively, compared to 13% and 31%, respectively, in 1990-2001. Conclusions Survival outcomes for MM patients who underwent high-dose chemotherapy and ASCT have significantly improved over the last 25 years. The best outcomes were noted in the 2012-2015 cohort, which coincides with improvements in supportive care, IMiD + PI-based induction, and widespread use of maintenance therapy. Older patients (age ≥65 years), advanced ISS Stage III disease, and patients with high-risk cytogenetics, had less favorable survival and novel strategies to improve outcomes are needed. Disclosures Bashir: Celgene: Research Funding; Purdue: Other: Advisory Board; KITE: Other: Advisory Board; Amgen: Other: Advisory Board; Takeda: Other: Advisory Board, Research Funding; Acrotech: Research Funding; StemLine: Research Funding. Nieto:Secura Bio: Other: Grant Support; Novartis: Other: Grant Support; Astra Zeneca: Other: Grant Support; Affimed: Consultancy, Other: Grant Support. Mehta:Kadmon: Research Funding; CSL Behring: Research Funding; Incyte: Research Funding. Hosing:NKARTA Inc.: Consultancy. Ciurea:Kiadis Pharma: Current equity holder in publicly-traded company, Research Funding. Popat:Bayer: Research Funding; Novartis: Research Funding. Khouri:Bristol Myers Squibb: Research Funding; Pfizer: Research Funding. Kebriaei:Ziopharm: Other: Research Support; Novartis: Other: Served on advisory board; Amgen: Other: Research Support; Pfizer: Other: Served on advisory board; Jazz: Consultancy; Kite: Other: Served on advisory board. Manasanch:Takeda: Honoraria; GSK: Honoraria; BMS: Honoraria; Sanofi: Honoraria; Quest Diagnostics: Research Funding; JW Pharma: Research Funding; Adaptive Biotechnologies: Honoraria; Novartis: Research Funding; Merck: Research Funding; Sanofi: Research Funding. Kaufman:Janssen: Research Funding; Karyopharm: Honoraria; Bristol Myers Squibb: Research Funding. Patel:Celgene: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Precision Biosciences: Research Funding; Poseida: Research Funding; Oncopeptides: Consultancy; Cellectis: Research Funding; Janssen: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Nektar: Consultancy, Research Funding. Shpall:Magenta: Membership on an entity's Board of Directors or advisory committees; Zelluna: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Adaptimmune: Membership on an entity's Board of Directors or advisory committees; Takeda: Other: Licensing Agreement. Lee:Celgene: Consultancy, Research Funding; Sanofi: Consultancy; GlaxoSmithKline: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Daiichi Sankyo: Research Funding; Regeneron: Research Funding; Genentech: Consultancy; Genentech: Consultancy; Takeda: Consultancy, Research Funding. Orlowski:Laboratory research funding from BioTheryX, and clinical research funding from CARsgen Therapeutics, Celgene, Exelixis, Janssen Biotech, Sanofi-Aventis, Takeda Pharmaceuticals North America, Inc.: Research Funding; Amgen, Inc., AstraZeneca, BMS, Celgene, EcoR1 Capital LLC, Forma Therapeutics, Genzyme, GSK Biologicals, Ionis Pharmaceuticals, Inc., Janssen Biotech, Juno Therapeutics, Kite Pharma, Legend Biotech USA, Molecular Partners, Regeneron Pharmaceuticals, Inc.,: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi-Aventis, Servier, Takeda Pharmaceuticals North America, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Founder of Asylia Therapeutics, Inc., with associated patents and an equity interest, though this technology does not bear on the current submission.: Current equity holder in private company, Patents & Royalties; STATinMED Research: Consultancy. Champlin:Johnson and Johnson: Consultancy; Cytonus: Consultancy; Actinium: Consultancy; Omeros: Consultancy; Genzyme: Speakers Bureau; DKMS America: Membership on an entity's Board of Directors or advisory committees; Takeda: Patents & Royalties. Qazilbash:Bioclinica: Consultancy; Amgen: Research Funding; Angiocrine: Research Funding; Bioline: Research Funding; Janssen: Research Funding.

Abstract: How to best use tyrosine kinase inhibitors (TKIs) of BCR-ABL after allogeneic stem cell transplantation for Philadelphia chromosome–positive acute lymphoblastic leukemia (ALL) is unknown but will almost certainly not be addressed by a definitive randomized trial. Saini and colleagues provide a large body of observational data to reinforce earlier circumstantial evidence favoring prophylactic use of TKIs for at least 2 years posttransplant.