Qazilbash, Muzaffar H.

ABSTRACTThe optimal conditioning schedule and CD34+ cell dose for autologous stem cell transplantation (ASCT) for AL amyloidosis is unknown. Patients (n = 1704) who underwent ASCT for AL amyloidosis between 2003 and 2020 in 9 centers were included. Data on melphalan conditioning dose, number of conditioning days, whether a rest day between conditioning and stem cell infusion was given or not, and infused CD34+ cell dose were collected. Full‐dose melphalan (≥ 180 mg/m2) was administered in 63.7% of the patients, and 80.4% had melphalan split into 2‐day conditioning. A rest day (day −1) between the conditioning regimen and stem cell infusion was provided in 52.5% of patients. The median infused CD34+ cell count was 4.7 × 106/kg. An infused CD34+ cell count ≥ 4.5 × 106/kg was associated with a shorter time to neutrophil and platelet engraftment. In a nominal regression analysis, full‐dose melphalan, 1‐day melphalan conditioning, and omitting a rest day between conditioning and stem cell infusion were independent predictors of post‐ASCT higher deep hematological response. The median follow‐up was 8.6 years, and 38% of patients died. Independent predictors of superior overall survival in multivariate Cox regression analysis included full‐dose melphalan, having no rest day, and infused CD34+ cells ≥ 4.5 × 106/kg. Independent predictors of higher day‐100 transplant‐related mortality (TRM) in nominal logistic regression analysis included poorer performance status, NT‐proBNP/BNP ≥ 1800/400 pg/mL, serum albumin < 2.5 g/dL, CD34+ cells < 4.5 × 106/kg, and not having a rest day. In conclusion, 1 day of melphalan conditioning and administration of CD34+ cells ≥ 4.5 × 106/kg are recommended for ASCT in AL amyloidosis.

Autologous stem cell transplantation (ASCT) in AL amyloidosis effectively produces a high overall hematological response rate, complete response rate, and durable remissions. However, it is a high-dose chemotherapy-based therapy with high morbidity which can be offered only to a subset of AL amyloidosis patients who are considered fit for this therapy. Transplant-related mortality (TRM) in AL amyloidosis has decreased over the past three decades due to improvement in patient selection. New therapeutic options question the utilization of ASCT. A model to predict TRM can improve the decision-making process, patient selection and further reduce TRM. AL amyloidosis patients (n=1718) from 9 centers globally, transplanted in the years 2003-2020 were included. Pre-ASCT variables of interest were assessed for association with Day-100 all-cause mortality, including age at ASCT (≥ 60 years), sex, light chain isotype, ECOG performance status (ECOG PS; 0, 1 and 2/3), the difference between involved and uninvolved light chains (dFLC; ≥180 mg/L), N-terminal prohormone of B natriuretic peptide (NT-proBNP; ≥1800 pg/mL) or B-type natriuretic peptide (BNP; ≥400 pg/mL), left ventricle ejection fraction (LVEF, &lt;50%), interventricular septum (&gt;16 mm), corrected diffusing capacity for carbon monoxide (cDLCO; ≤65% of predicted), forced expiratory volume in one second (FEV1; ≤65% of predicted), serum albumin (&lt;2.5 g/dL), estimated glomerular filtration rate (eGFR; &lt;30 mL/min/m2), alkaline phosphatase (&gt;X2 upper limit of normal), and systolic blood pressure (&lt;100 mmHg). Troponins could not be included in our modeling given the multitude of assays used across institutions and periods that could not be reconciled. A random forest (RF) classifier with 10-fold cross-validation was used to assist in variable selection. The final model variables were selected based on statistical performance and clinical relevance. The model was fitted using logistic regression. The median age at ASCT was 58, and 40% of patients were women. The most frequently involved organs were the kidneys (69%) and the heart (52%). Mayo 2004 stages I and II were collectively present in 83% of patients. Day-100 TRM occurred in 75 patients (4.4%) with the 3 main causes being shock (n=27), cardiac arrhythmia (n=26), and organ failure (n=22). Age at ASCT, sex, and light chain isotype were not predictors of Day-100 TRM. Across the other pre-ASCT variables, adverse features were present from 6.9% (LVEF &lt;50%) to 25.8% (dFLC ≥180 mg/L) of patients. Ten factors were associated with Day-100 TRM on univariate analysis. The odds ratio of these variables ranged from 1.6 to 10.2. RF classifier using all these variables identified a model with an area under the curve (AUC) of 0.72±0.12. Using the importance hierarchy function to refine the model selection, a 4-variable model [NT-proBNP/BNP ≥1800/400 pg/mL, serum albumin &lt;2.5 g/dL, ECOG PS 1 or 2/3, and systolic blood pressure &lt;100 mmHg] was built with an AUC of 0.70±0.12. Based on logistic regression coefficients, ECOG PS 2/3 was assigned two points, while other adverse predictors were assigned 1-point each (model score range 0-5). We then applied the model scoring to our study population. Score distribution was as follows: 0 (n=431, 25.1% of patients), 1 (n=688,40.1%), 2 (n=413, 24.0%), and 3 and above (n=186, 10.8%). Day-100 TRM rates were 0.46%, 3.2%, 5.8%, and 14.5% for 0, 1, 2, and ≥3 points, respectively. The respective rates for the years 2003-2011 were 1.1%, 3.3%, 6.4%, and 19.2%, while for the years 2012-2020 0%, 3.1%, 5.2%, and 8.4%. We developed a simple clinical tool to predict the Day-100 TRM risk in AL patients undergoing ASCT. This tool will allow more informed decision making weighing the individual benefits and risks of ASCT compared to other therapies.

Introduction: High dose chemotherapy and autologous stem cell transplantation (ASCT) is one of the most effective therapies in light chain (AL) amyloidosis. It is associated with a high hematologic response rate and leads to durable remissions. High dose melphalan is the most frequently used conditioning chemotherapy, as has been used in multiple myeloma (MM). Melphalan dose is based on renal function, age, degree of cardiac involvement and patients' frailty and is predictive of outcomes. While studies that assessed the conditioning schedule have been conducted in MM, with variable results, no such studies were done in AL amyloidosis. Methods: In this retrospective study, we explored the impact of the conditioning schedule on post-transplant outcomes in a large multicenter study. Patients with AL amyloidosis who underwent ASCT for the primary diagnosis of AL amyloidosis between January 1, 2003, and December 31, 2020, were included in this study. Results: One thousand seven hundred and eighteen (n=1718) patients from 9 centers are included. The median age was 58 years, and 61% were male. Most patients had one (43%) or two (33%) involved organs, with the most involved organs were the kidneys (69%) followed by the heart (52%). Induction therapy was given to 52% of patients. The conditioning regimen was almost exclusively melphalan (99.2%), with 65% receiving full dose melphalan (≥170 mg/m 2). Melphalan was given over two days in most patients (80%). A rest day between conditioning and stem cell infusion was provided in 53% of patients, mostly in those who received melphalan on a single day rather than over 2 days (87% vs 44%, P&lt;0.001). Post-transplant hematologic response was available for 1569 patients (91% of patients) and were assessed from baseline. Complete response (CR) and very good partial responses (VGPR) were achieved post-ASCT in 33.7% of patients each. Low dFLC-partial response (PR) was achieved in 2.7% and PR in 18% of patients. Altogether, satisfactory post-ASCT response (CR, VGPR, or low-dFLC PR combined) was achieved in 70% of patients. Compared to no induction, less than a PR to induction was associated with a lower probability of achieving satisfactory post-ASCT response, while PR or better to induction had higher chances of satisfactory post-ASCT response (65% vs 46% vs 84%, P&lt;0.001). A single day of melphalan conditioning was associated with a higher probability of satisfactory post-ASCT response compared to two days of conditioning (82% vs 67%, P&lt;0.001). Omitting a day of rest between conditioning and stem cell infusion was also associated with higher satisfactory post-ASCT response compared to having a rest day (76% vs 65%, P&lt;0.001). The Table lists other predictors for a post-ASCT satisfactory hematologic response. In a nominal multivariate logistic regression analysis, independent predictors for higher post-ASCT satisfactory hematological response rate included: PR or better to induction therapy, female gender, kappa light chain isotype, lower dFLC at baseline, and kidney and liver involvement. In addition, full dose melphalan, conditioning given over a single day and having no rest day between conditioning and stem cell infusion were also associated with a higher likelihood of satisfactory post-ASCT response. Post-ASCT hematologic CR rate was higher in those receiving full dose conditioning (36% vs 28%, P&lt;0.001), in those having no rest day (40% vs 28%, P&lt;0.001) but not in those who received one day of conditioning versus two days (35% vs 33%, P=0.5). The rate of ICU admission was higher in those receiving no day rest (17.7% vs 12.6%), P=0.003) and among those who received reduced dose melphalan (18.1% vs 13.3%, P=0.008) but not based on number of conditioning days (P=0.56). Day 100 mortality was significantly higher in the no rest day group (5.6% vs 3.2%, P=0.01) and among those receiving reduced dose melphalan (6.8% vs 3.1%, P=0.004) compared to their counterparts, but not based on the number of days of conditioning (P=0.89). The median follow-up in the entire cohort was 104 months (95% CI 98-110). In a multivariate analysis for overall survival (OS), the conditioning dose but not the conditioning schedule was independently associated with OS. Conclusions: This study is the first to demonstrate the effect of melphalan conditioning schedule on post-transplant response. This study supports a single day melphalan conditioning in AL amyloidosis to improve post-ASCT response.

AbstractBackgroundLenalidomide maintenance after autologous stem cell transplant (ASCT) in multiple myeloma (MM) results in superior progression‐free survival and overall survival. However, patients with high‐risk multiple myeloma (HRMM) do not derive the same survival benefit from lenalidomide maintenance compared with standard‐risk patients. The authors sought to determine the outcomes of bortezomib‐based maintenance compared with lenalidomide maintenance in patients with HRMM undergoing ASCT.MethodsIn total, the authors identified 503 patients with HRMM who were undergoing ASCT within 12 months of diagnosis from January 2013 to December 2018 after receiving triplet novel‐agent induction in the Center for International Blood and Marrow Transplant Research database. HRMM was defined as deletion 17p, t(14;16), t(4;14), t(14;20), or chromosome 1q gain.ResultsThree hundred fifty‐seven patients (67%) received lenalidomide alone, and 146 (33%) received bortezomib‐based maintenance (with bortezomib alone in 58%). Patients in the bortezomib‐based maintenance group were more likely to harbor two or more high‐risk abnormalities and International Staging System stage III disease (30% vs. 22%; p = .01) compared with the lenalidomide group (24% vs. 15%; p < .01). Patients who were receiving lenalidomide maintenance had superior progression‐free survival at 2 years compared with those who were receiving either bortezomib monotherapy or combination therapy (75% vs. 63%; p = .009). Overall survival at 2 years was also superior in the lenalidomide group (93% vs. 84%; p = .001).ConclusionsNo superior outcomes were observed in patients with HRMM who received bortezomib monotherapy or (to a lesser extent) in those who received bortezomib in combination as maintenance compared with lenalidomide alone. Until prospective data from randomized clinical trials are available, post‐transplant therapy should be tailored to each patient with consideration for treating patients in clinical trials that target novel therapeutic strategies for HRMM, and lenalidomide should remain a cornerstone of treatment.

Abstract The overall survival (OS) has improved significantly in multiple myeloma (MM) over the last decade with the use of proteasome inhibitor and immunomodulatory drug-based combinations, followed by high-dose melphalan and autologous hematopoietic stem cell transplantation (auto-HSCT) and subsequent maintenance therapies in eligible newly diagnosed patients. However, clinical trials using auto-HSCT followed by lenalidomide maintenance have shown an increased risk of second primary malignancies (SPM), including second hematological malignancies (SHM). We evaluated the impact of SPM and SHM on progression-free survival (PFS) and OS in patients with MM after auto-HSCT using CIBMTR registry data. Adult patients with MM who underwent first auto-HSCT in the United States with melphalan conditioning regimen from 2011 to 2018 and received maintenance therapy were included (n = 3948). At a median follow-up of 37 months, 175 (4%) patients developed SPM, including 112 (64%) solid, 36 (20%) myeloid, 24 (14%) SHM, not otherwise specified, and 3 (2%) lymphoid malignancies. Multivariate analysis demonstrated that SPM and SHM were associated with an inferior PFS (hazard ratio [HR] 2.62, P &lt; .001 and HR 5.01, P &lt; .001, respectively) and OS (HR 3.85, P &lt; .001 and HR 8.13, P &lt; .001, respectively). In patients who developed SPM and SHM, MM remained the most frequent primary cause of death (42% vs 30% and 53% vs 18%, respectively). We conclude the development of SPM and SHM leads to a poor survival in patients with MM and is an important survivorship challenge. Given the median survival for MM continues to improve, continued vigilance is needed to assess the risks of SPM and SHM with maintenance therapy post–auto-HSCT.

Abstract Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with historically poor outcomes and no worldwide consensus treatment approach. Unique among most hematologic malignancies for its frequent cutaneous involvement, BPDCN can also invade other extramedullary compartments, including the central nervous system. Generally affecting older adults, many patients are unfit to receive intensive chemotherapy, and although hematopoietic stem cell transplantation is preferred for younger, fit individuals, not all are eligible. One recent therapeutic breakthrough is that all BPDCNs express CD123 (IL3Rα) and that this accessible surface marker can be pharmacologically targeted. The first-in-class agent for BPDCN, tagraxofusp, which targets CD123, was approved in December 2018 in the United States for patients with BPDCN aged ≥2 years. Despite favorable response rates in the frontline setting, many patients still relapse in the setting of monotherapy, and outcomes in patients with relapsed/refractory BPDCN remain dismal. Therefore, novel approaches targeting both CD123 and other targets are actively being investigated. To begin to formally address the state of the field, we formed a new collaborative initiative, the North American BPDCN Consortium (NABC). This group of experts, which includes a multidisciplinary panel of hematologists/oncologists, hematopoietic stem cell transplant physicians, pathologists, dermatologists, and pediatric oncologists, was tasked with defining the current standard of care in the field and identifying the most important research questions and future directions in BPDCN. The position findings of the NABC’s inaugural meetings are presented herein.

8057 Background: Following autologous hematopoietic stem cell transplant (auto HCT), maintenance therapies improve survival, reduce relapse risk in multiple myeloma (MM), and are the de facto standard-of-care. However, clinical trials have shown an increased risk of second primary malignancies (SPM) with maintenance therapy, including second hematological malignancies (SHM). We examined data from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry to evaluate the impact of SPM on progression-free (PFS) and overall survival (OS) and the utilization of allogeneic HCT in patients with therapy-related myeloid neoplasms (t-MN). Methods: Adult patients (pts) with MM who underwent first auto HCT in the United States with a melphalan conditioning regimen from 2011-2018 and subsequently received maintenance therapy were included (N=3948). The primary endpoint of interest was the impact of SPM and SHM on OS. Multivariate analytic (MVA) modelling was applied, accounting for competing risks while integrating significant covariates to determine the impact of SPM on PFS and OS. Finally, we studied the utilization and survival following allogeneic HCT for SHM. Results: Baseline characteristics were similar between the two groups. Maintenance regimens used were lenalidomide (2836, 72%), bortezomib (370,9 %) or lenalidomide + bortezomib (372, 9%) based combinations. At a median follow up of 37 months, 175 (5%) pts developed SPM, including 112 (64%) solid 36 (21%) myeloid, and 27 (15%) lymphoid cancers. In MVA, the development of SPM and SHM was associated with an inferior PFS (HR 2.62, P<0.001 and HR 5.01, P<0.001, respectively) and OS (HR 3.85, P<0.001 and 8.13, P<0.001, respectively). The two commonest causes of death were MM (42%) and SPM (30%) for those developing SPM. Similarly, MM (53%) and SHM (18%) were the two commonest causes of death for those developing SHM. Nine (14%,5 t-MDS and 4 t-AML) of 63 patients with SHM underwent an allogeneic HCT. Patients undergoing allogeneic HCT were more likely to have Karnofsky score ≥90 (100% vs. 50%, P=0.02) compared to those who did not. One year survival from allo SCT was 66.7% (CI 34.6-92%). Conclusions: The three-year cumulative incidence of SPM was 3.3 (2.6-4)% in this large contemporaneous CIBMTR cohort. Disease relapse remains the primary cause of death in MM patients who develop SPM or SHM. Given the median OS for MM is now > 10 years, longer follow-up is needed to assess the SPM and SHM risks with maintenance therapy post-auto HCT.

Abstract Introduction POEMS syndrome is a rare disease associated with a plasma cell dyscrasia with limited information regarding the role of ASCT. Small single institution series have demonstrated deep and durable responses after ASCT along with neurological improvement. Despite these benefits, ASCT is thought to have higher treatment related morbidity and mortality, limiting its use. We describe the outcomes from an international multicenter database of patients with POEMS syndrome undergoing ASCT. Methods We performed a retrospective analysis using the Center for International Blood and Marrow Transplant Research (CIBMTR) database to evaluate the outcomes of patients undergoing ASCT for POEMS syndrome. Standard descriptive methods were used to report patient characteristics. Univariate and multivariate analysis were performed to identify predicators for non-relapse mortality (NRM), relapse, progression-free and overall survival (PFS, OS). NRM was compared between POEMS and multiple myeloma (MM) patients who underwent ASCT during the same time period. Results Between 2008-2018, 331 pts with POEMS syndrome who underwent ASCT were identified. The median age was 51 years, with 66% males. Racial distribution was 65% Caucasians, 19% African American, 5% other, and 10% missing. Pre-transplant characteristics included 70% patients had Karnofsky score &lt;90, and 50% had HCT-CI ≥ 3, reflecting underlying disease severity and symptoms. The most common comorbidity was pulmonary (52%). Only 14% of patients were in very good partial response or better at the time of ASCT and 72 (22%) patients underwent ASCT without prior treatment. The median time from diagnosis to ASCT was 7 months and 74% underwent ASCT within 12 months of diagnosis. The most common mobilization strategy was GCSF +/- plerixafor in 50% of pts and 87% of pts received conditioning with 200mg/m2 of Melphalan. The median follow up was 48 (range 3-137) months. At day 100, NRM was 0.9 % (95% CI: 0.2-2.2%). At 4 years, NRM was 4.9% (95% CI: 2.6-7.9%), relapse 15.4% (95% CI 11.3-20.1%), PFS 79.7% (95% CI 74.5-84.3%) and OS 92% (95% CI 89.2-95.6%). Subsequent neoplasms were seen in 16 (5%) with 4 myeloid malignancy and 12 solid tumors. On multivariate analysis, age ≥ 60 years was associated with greater hazards of mortality, HR 2.6 (95% CI 1.2-5.6), p 0.01. The figure shows the comparable NRM between POEMS and MM (p 0.31). Conclusions: We report outcomes of the largest ASCT series of POEMS patients. Despite a high HCT-CI and low functional status among patients with POEMS syndrome, no difference in NRM was seen when compared to MM. Post-transplant outcomes were excellent and support single center data on the role of ASCT in this rare disease. Figure 1 Figure 1. Disclosures Kansagra: Oncopeptides: Membership on an entity's Board of Directors or advisory committees; 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; BMS: Membership on an entity's Board of Directors or advisory committees; Alynylam: Membership on an entity's Board of Directors or advisory committees; Cota Health: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees. Dispenzieri: Alnylam: Research Funding; Pfizer: Research Funding; Sorrento Therapeutics: Consultancy; Takeda: Research Funding; Oncopeptides: Consultancy; Janssen: Consultancy, Research Funding. Kumar: Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; BMS: Consultancy, Research Funding; Oncopeptides: Consultancy; Beigene: Consultancy; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche-Genentech: Consultancy, Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Antengene: Consultancy, Honoraria; Novartis: Research Funding; Bluebird Bio: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Research Funding; Carsgen: Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Tenebio: Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding. Qazilbash: Bristol-Myers Squibb: Other: Advisory Board; NexImmune: Research Funding; Janssen: Research Funding; Biolline: Research Funding; Oncopeptides: Other: Advisory Board; Angiocrine: Research Funding; Amgen: Research Funding. Shah: GSK: Consultancy; Karyopharm: Consultancy; Oncopeptides: Consultancy; Indapta Therapeutics: Consultancy; Janssen: Research Funding; Nektar: Research Funding; Bluebird Bio: Research Funding; Teneobio: Research Funding; CareDx: Consultancy; BMS/Celgene: Research Funding; Sanofi: Consultancy; Sutro Biopharma: Research Funding; CSL Behring: Consultancy; Poseida: Research Funding; Precision Biosciences: Research Funding; Amgen: Consultancy; Kite: Consultancy. D'Souza: Sanofi, Takeda, Teneobio, CAELUM, Prothena: Research Funding; Imbrium, Pfizer, BMS: Membership on an entity's Board of Directors or advisory committees; Janssen, Prothena: Consultancy.

Abstract Background: Autologous stem cell transplantation (ASCT) in multiple myeloma (MM) has been shown to improve survival compared to conventional chemotherapy alone. However, the ability to perform ASCT relies, in part, on collecting a sufficient number (#) of CD34+ hematopoietic stem cells (HSCs), typically from peripheral blood. The ideal HSC mobilization regimen would enable collection of optimal #s of HSCs (5-6x10 6 CD34+ cells/kg) within the minimum # of apheresis sessions possible. Yet, despite currently available G-CSF (G) based mobilization regimens and multiple apheresis days, many remain unable to collect optimal #s of HSCs. Motixafortide (M) is a novel CXCR4 inhibitor, with high affinity (IC 50 0.54-4.5 nM) and long receptor occupancy (&gt;48 hours). Methods: In this prospective, phase 3, double blind, placebo controlled, multicenter trial, 122 patients were randomized (2:1) to receive either M+G or placebo (P)+G for HSC mobilization prior to ASCT for MM. All patients received G (10 mcg/kg) on days 1-5 (and 6-8, if needed). Patients received either M (1.25 mg/kg, subcutaneous injection) or P on day 4 (and 6, if needed). Apheresis began day 5, with the primary (PEP) and secondary (SEP) endpoints of collecting ≥6x10 6 CD34+ cells/kg in up to 2 apheresis days or 1 day, respectively. Apheresis continued on days 6-8 if needed. Total CD34+ cells/kg were analyzed on site to determine if patients mobilized to the goal and all samples were subsequently sent for assessment by central laboratory. Patients that did not collect ≥2x10 6 CD34+ cells/kg by day 8 proceeded to rescue mobilization. The # of CD34+ cells infused was determined independently by each investigator according to local practice (minimum ≥2x10 6 CD34+ cells/kg). Analyses of the PEP/SEPs were performed on an intent-to-treat basis. Results: Demographics between the 2 treatment arms were similar. Mobilization with M+G resulted in 92.5% of patients collecting ≥6x10 6 CD34+ cells/kg within 2 apheresis days vs 26.2% with P+G (Odds Ratio (OR) 53.3, 95% CI 14.12-201.33, p&lt;0.0001). Furthermore, 88.8% of patients with M+G collected ≥6x10 6 CD34+ cells/kg in 1 apheresis day vs 9.5% with P+G (OR 118.0, 95% CI 25.36-549.35, p&lt;0.0001); and 96.3% with M+G collected ≥2x10 6 CD34+ cells/kg within 1 apheresis day vs 64.3% with P+G (OR 18.9, 95% CI 4.47-80.04, p&lt;0.0001). The PEP and SEPs were confirmed as statistically significant by central laboratory (all respective p-values &lt;0.0001). The median # of HSCs mobilized in 1 apheresis day with M+G was 10.80x10 6 CD34+ cells/kg vs 2.14x10 6 CD34+ cells/kg with P+G. The # of cells infused was determined independently by each investigator according to local practice. Median time to neutrophil engraftment was 12 days in both arms (HR 0.94, 95% CI 0.62-1.41, p=0.75). Median time to platelet engraftment was 18 days (range: 17-19) with M+G and 17 days (range: 17-18) with P+G (HR 0.89, 95% CI 0.59-1.34, p=0.57). Graft durability at day 100 post-ASCT was 92.2% in the M+G arm and 91.9% in the P+G arm (OR 1.04, 95% CI 0.2-4.5, p=0.96). Overall, adverse events were reported in 98.8% (Grade 3/4: 68.8%) of patients with M+G vs 95.2% (Grade 3/4: 42.9%) with P+G, with cytopenias in the post-ASCT period prior to engraftment accounting for the majority of Grade 3/4 AEs in both arms, as expected. The most common AEs related to M included: local injection site reactions (any grade: 70.0%, Grade 3/4: 11.3%); and systemic reactions such as pruritis (33.8%), flushing (32.5%) and urticaria (12.5%). Additionally, mobilization with M+G resulted in a 10.5x increase in mean absolute # of CD34+CD45RA-CD123loCD38-CD90+CD49f+ primitive HSCs collected vs P+G (p&lt;0.0001). Multicolor FACS and scRNA sequencing of CD34+ HSCs from both arms will be reported in a separate ASH abstract. Conclusions: A single injection of M on top of G significantly increased the proportion of patients mobilizing ≥6x10 6 CD34+ cells/kg for ASCT (92.5%) vs G (26.2%) in up to 2 apheresis days (p&lt;0.0001), while enabling 88.8% to collect ≥6x10 6 CD34+ cells/kg in just 1 apheresis (p&lt;0.0001, Figure 1A). Despite the higher # of cells mobilized by M+G, the # of CD34+ cells/kg infused was determined independently by each investigator according to local practice with comparable engraftment kinetics and graft durability between the 2 arms. Finally, M+G mobilized 10.5x more immunophenotypically primitive CD34+ HSCs capable of durable multilineage hematopoietic engraftment vs P+G (p&lt;0.0001, Figure 1B). Figure 1 Figure 1. Disclosures Crees: BioLineRx Ltd.: Research Funding. Larson: TORL biotherapeutics: Current holder of individual stocks in a privately-held company; Bioline: Research Funding; Abbvie: Research Funding; BMS: Research Funding; Celgene: Research Funding; GSK: Research Funding; Janssen: Research Funding; Juno: Research Funding; Novartis: Research Funding; Pfizer: Research Funding; Takeda: Research Funding. Illés: Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees. Stiff: Incyte: Research Funding; Cellectar: Research Funding; Seagen: Research Funding; Gamida Cell: Research Funding; Cellectar: Research Funding; Actinium: Research Funding; Bristol Myers Squibb: Research Funding; BioLineRX: Research Funding; Macrogenics: Research Funding; CRISPR Therapeutics: Consultancy, Honoraria; Amgen: Research Funding; Janssen: Research Funding; Kite, a Gilead Company: Research Funding; Karyopharm: Consultancy, Honoraria; MorphoSys: Consultancy, Honoraria. Sborov: Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Consultancy; Sanofi: Consultancy; SkylineDx: Consultancy. Pereira: Jazz Pharmaceutical: Membership on an entity's Board of Directors or advisory committees. Mikala: Novartis: Consultancy; Takeda: Consultancy; Abbvie: Consultancy; Krka: Consultancy; Janssen: Consultancy; Amgen: Consultancy; Celgene: Consultancy. Holtick: Celgene: Honoraria; Sanofi: Honoraria. Qazilbash: Amgen: Research Funding; Oncopeptides: Other: Advisory Board; Bristol-Myers Squibb: Other: Advisory Board; Biolline: Research Funding; Angiocrine: Research Funding; NexImmune: Research Funding; Janssen: Research Funding. Hardy: American Gene Technologies, International: Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Membership on an entity's Board of Directors or advisory committees; InCyte: Membership on an entity's Board of Directors or advisory committees. Vainstein: BioLineRx LTD: Current Employment. Sorani: BioLineRx LTD: Current Employment. Gliko-Kabir: BioLineRx Ltd.: Current Employment. Goldstein: BioLineRx Ltd.: Current Employment. Kadosh: BioLineRx Ltd.: Current Employment.