Abstract: Background: The role of autologous stem cell transplantation (ASCT) in follicular lymphoma (FL) in the rituximab era remains undefined. Although ASCT has demonstrated to improve outcomes in relapsed/refractory (R/R) FL, there are very few studies addressing this issue in patients who had prior exposure to rituximab. Our aim was thus to assess the outcome of ASCT in FL patients in the modern era. Methods and Patients: We conducted a single center retrospective analysis of patients who underwent ASCT for follicular lymphoma at the Cleveland Clinic. Patient and disease characteristics were examined and prognostic factors for survival were determined using univariate and multivariate Cox analysis. Results: Total of 127 patients with a confirmed diagnosis of FL underwent ASCT at our institution between March 2000 and October 2013. Study population was predominantly male (61%) and Caucasian (92%). Median age at transplant was 55 years. Majority of the patients had FL grade of 1-2 (88%), International Prognostic Index (IPI) 0-2 (81%), and stage IV disease (60%) at the time of diagnosis. All, but 9 patients (93%) received rituximab as part of their prior treatment and 53% had received ³3 prior therapies. Disease status prior to transplant was 1st partial response (PR1) (9%), 2nd complete remission (CR2) (24%), 2nd PR (PR2) (60%), and R/R (8%); no patients received transplant in the 1st CR (CR1). An uniform preparative regimen consisting of Busulfan, Cyclophosphamide and Etoposide (Bu/Cy/VP16) was used in all patients. Median CD34+ cell dose was 7.49 x 106/kg. Median days to neutrophil engraftment were 10 days and platelet engraftment was 14 days. In our cohort, 10-year progression free survival (PFS) and overall survival (OS) were 33.2% and 52.4% respectively. Disease relapsed in 58/127 (46%) of the patients and 67% were alive at the time of last follow up. Age at transplant (Figure 1) and number of prior therapies, 〉 3 vs 1-3 (Figure 2) were significant prognostic factors for OS, in both univariate and multivariate analyses. Higher age (HR 1.76, 95% CI 1.23-2.52, p=0.002) and 〉 3 prior therapies (HR 2.58, 95% CI 1.31-5.12, p=0.006) were predictive for inferior OS. Disease status at transplant, IPI, and stage had no impact on survival. Disease relapse (67%) and secondary malignancies (7.1%) were the leading causes of death. Conclusions: In our analysis, a durable PFS, median of 49 months, was observed in patients with R/R FL who underwent an ASCT in the rituximab era. Age at transplant and number of prior therapies were identified as poor prognostic factors for OS. These data suggest that ASCT should be considered in young patients with R/R FL early in their disease course. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Hill: Millenium: Research Funding; Novartis: Research Funding.

Abstract: Introduction: Allogeneic stem cell transplant is an intensive procedure, offered in a limited number of medical centres. We sought to describe how sociodemographic variables impacted access to transplant across the United States, and if disadvantaged populations had inferior access to transplant. Methods: Data from the Surveillance, Epidemiology and End Results Program (SEER) and the Center for International Blood and Marrow Transplant Research (CIBMTR) was integrated to determine the rate of unrelated donor transplantation between 2000 and 2010 in each of the 612 counties included in the SEER registry. Patients under the age of 65 with AML, ALL, and MDS were included, and the analysis was restricted to unrelated donors due to limited availability of ZIP code in CIBMTR data. New incident cases were determined from SEER, and the number of transplants was determined from CIBMTR. The transplant rate was calculated (transplants performed divided by incident cases) for each county. County attributes (percent minority, rural/urban status, percentage below the poverty line, and median family size) were obtained from US Census data. Poisson regression was used to describe how county attributes impacted transplant rates. Transplant rates were calculated separately for AML, White residents, and pediatric ALL. Results: 3147 patients were identified in the CIBMTR dataset that met inclusion criteria. The estimated ZIP code completeness was 75%. There were 30,468 new incident diagnoses of ALL, AML, and MDS. For AML, patients from rural areas (less than 20,000 residents) and patients from areas with higher poverty levels had lower transplant rates (Table 1). Minority status and family size did not impact transplant rate. In regression models, higher levels of poverty remained associated with lower transplant rates, while rurality did not (Table 2). The results were similar among White residents. In contrast, in pediatric ALL, no county attributes (poverty, rurality, percent minority, and family size) were significantly associated with a difference in transplant rate (Table 1). However, numbers of transplants were smaller, limiting power. Discussion: Patients with AML from disadvantaged areas had lower rates of unrelated donor transplant. While patients from disadvantaged areas were also more likely to be non-White, and non-White Americans are less likely to have an available unrelated donor, this difference was also seen in White Americans from disadvantaged areas. This suggests the lower transplant rate is due impaired access to transplant. Poverty rate was the most important predictor of transplant rate. The results of this study suggest that improving access to transplant in disadvantaged populations should be a priority for health care administrators. Based on these results, approximately 2500 Americans do not undergo allogeneic transplant annually due to inferior access associated with higher poverty rates. Table 1 Univariate Analysis Table 1. Univariate Analysis Table 2 Acute Myeloid Leukemia, Regression Model * Metropolitan = county 〉 50,000 people, micropolitan = county 〉 20,000, rural county 〈 20,000. Table 2. Acute Myeloid Leukemia, Regression Model. / * Metropolitan = county 〉 50,000 people, micropolitan = county 〉 20,000, rural county 〈 20,000. Disclosures Hahn: Novartis: Equity Ownership; NIH: Research Funding.

Abstract: AML and MDS are heterogeneous myeloid neoplasms with variable biologic and clinical outcomes. Although allogeneic HCT is the only potentially curative therapy for high risk AML and MDS, survival after transplant remains poor, and identifying who benefits is challenging. We hypothesized that next-generation sequencing (NGS) mutational analyses can predict outcome in MDS and AML patients undergoing allogeneic HCT. We performed multi-amplicon targeted pre-HCT NGS using a somatic panel of the 60 most commonly mutated genes in myeloid neoplasias as previously determined by whole exome sequencing, on 123 patients with AML (N=64, 52%) and MDS (N=59, 48%) who subsequently underwent HCT. Median age at transplant was 53 years (range, 20-73). 21 (17%) patients had complex karyotype, 10 (8%) with monosomy 7, 48 (39%) normal, and 48 (39%) with other or unknown cytogenetic abnormalities. 45 (37%) patients were in a complete remission (CR) prior to transplant, while 78 (63%) were in less than a CR; with CR as defined by International Working Group criteria for MDS, or 〈 5% blasts for AML. The majority of patients received myeloablative conditioning (N=83, 68%), and 40 (33%) received a reduced-intensity preparative regimen. Donor source was matched sibling (N=52, 42%), matched unrelated (N=56, 46%), cord-blood (N=12, 10%), and haplo-identical (N=3, 2%). Median follow up was 35 months (range 5-178). Mutations were analyzed individually and by molecular pathway. 88 (72%) patients had at least one mutation, most frequently in STAG2 (10.2%), TET2 (9.8%), ASXL1 (8.1%), and RUNX1 (8.1%). TP53 mutations were more common in MDS patients compared to AML (10% versus 1.6%, P=0.05). NRAS (P=0.019) and TP53 (P=0.022)mutations were more commonly associated with complex karyotype. Mutations in BCOR (P=0.048) and TP53 (P=0.047)were associated with less than CR, while TET2 (P=0.03)mutations were associated with CR prior to HCT. In univariable analyses, the presence of complex karyotype was associated with shorter overall (OS) and relapse-free survival (RFS) (hazard ratio [HR] 2.4; P=0.002 and HR 3.1; P 〈 0.001). Mutations in TET2 (HR 2.1; P=0.042) and EZH2 (HR 2.3; P=0.048), or presence of any mutation in the histone modification pathway (ASXL1, EZH2, KDM6A, SUZ12); (HR 1.7; P=0.039) was associated with poor OS. The presence of any mutation in the DEAD box RNA-helicase family genes (DHX29, DDX54, DDX41) was associated with poor RFS (HR 3.1; P=0.009). Nothing except complex karyotype was specifically associated with higher relapse. Unlike in previous reports, TP53 mutations were not found to be significantly associated with poor OS or RFS, though these cases (N=7) were limited. In multivariable analyses, adjusting for clinical variables, complex karyotype remained significantly associated with poor OS (HR 2.7; P 〈 0.001) and RFS (HR 3.9; P 〈 0.001). TET2 also remained independently associated with poor OS (HR 2.4; P=0.022). Presence of any of the DNA methylation mutations (TET2, DNMT3A, IDH1, IDH2) was associated with poor RFS (HR 1.7; P=0.05). 3-year OS was 23% in patients with a complex karyotype versus 48% in patients without (P=0.002); and 14% in patients with a TET2 mutation and 46% without (P=0.042) (Figure 1). Molecular abnormalities are important variables in determining outcome after allogeneic HCT. We demonstrate that TET2 mutations in AML and MDS predict for poor survival after HCT. Ongoing serial mutational analyses in an extended cohort of patients will enhance our understanding of the role of NGS in informing care decisions for patients undergoing allogeneic HCT for AML and MDS. Figure 1. Overall Survival by TET2 mutation status Figure 1. Overall Survival by TET2 mutation status Disclosures Majhail: Gamida Cell Ltd.: Consultancy; Anthem Inc.: Consultancy. Sekeres:Celgene Corporation: Membership on an entity's Board of Directors or advisory committees.

Abstract: The lower morbidity and mortality of reduced-intensity conditioning (RIC) regimens has allowed allogeneic hematopoietic cell transplantation (HCT) in older patients. Unrelated umbilical cord blood (UCB) has been investigated as an alternative stem cell source because of insufficient availability of suitably HLA matched related (MRD) and adult volunteer unrelated donors. We hypothesized that RIC HCT using UCB would be safe and efficacious in older patients and compared the transplant related mortality (TRM) and overall survival (OS) after RIC HCT in patients older than 55 years using either MRD (n=47) or, in patients with no 5/6 or 6/6 HLA compatible related donors, UCB (n=43). RIC regimen consisted of total-body irradiation (200 cGy) and either cyclophosphamide and fludarabine (n=69), or busulfan and fludarabine (n=16) or busulfan and cladribine (n=5). The median age of MRD and UCB cohorts was 58 (range, 55–70) and 59 (range, 55–69) years, respectively. AML/MDS (50%) was the most common diagnosis. All MRD grafts were 6 of 6 HLA matched to the recipient. Among patients undergoing UCB HCT, 38 (88%) received two UCB units to optimize cell dose and 40 (93%) received 1–2 HLA mismatched grafts. The median total nucleated cell dose was 9.2 × 108/kg (range, 3.0–21.2) for MRD grafts and 0.4 × 108/kg (range, 0.2–0.8) for UCB grafts. The median followup for survivors was 27 (range, 12–61) months. The probability of progression-free survival (PFS) at 3-years for recipients of MRD and UCB was 30% (95% confidence intervals [CI], 16–44%) and 34% (95% CI, 19–48%)(p=0.98) and OS was 43% (95% CI, 29–58%) and 34% (95% CI, 17–50%)(p=0.57), respectively. The cumulative incidence of sustained donor engraftment at 6 weeks was 100% for MRD and 89% (95% CI, 80–99%) for UCB recipients (p=0.05). The cumulative incidence of grade 2–4 acute graft-versus-host disease (GVHD, 42% vs. 49%, p=0.20) and TRM at 180-days (23% vs. 28%, p=0.36) was comparable between the MRD and UCB groups; however, UCB recipients had a lower incidence of chronic GVHD at 1-year (40% vs. 17%, p=0.02). On multivariate analysis, graft type (MRD vs. UCB) had no impact on TRM, PFS or OS; only HCT comorbidity index score was independently predictive for these endpoints. For the whole cohort, 180-day TRM for patients with HCT comorbidity index scores of 0, 1–2 and ≥ 3 was 14% (95% CI, 0–28%), 19% (95% CI, 5–32%) and 44% (95% CI, 26–62%), respectively. Compared to patients with a higher score, patients with a score of 0–2 had lower TRM (hazard ratio [HR] 0.3 [95% CI, 0.1–0.7]) as well as better PFS (HR 0.5 [95% CI, 0.3–0.9]) and OS (HR 0.5 [95% CI, 0.2–0.9] ). Our study supports the use of HLA mismatched UCB as an alternative graft source for older patients who need a transplant but do not have a MRD. The use of RIC and UCB extends the availability of transplant therapy to older patients previously excluded on the basis of age and lack of a suitable MRD. Older HCT candidates with limited comorbidity have a low and acceptable risk of TRM and a careful review of existing comorbidities is necessary when considering older patients for HCT.

Abstract: Background Myeloablative conditioning (MAC) is a standard approach for allogeneic hematopoietic cell transplantation (alloHCT), but is associated with risks of morbidity and mortality. As regimen intensity affects post-transplant outcomes, assessment of pre-transplant cytogenetics and somatic mutations may refine which acute myeloid leukemia (AML) patients benefit the most. We compared the effectiveness of two approaches: busulfan/cyclophosphamide (Bu/Cy) and the MAC, but reduced toxicity regimen busulfan/fludarabine (Bu/Flu). Moreover, it is unclear whether somatic mutations in AML may differentially affect post-transplant outcomes between these regimens. We hypothesized that despite relative differences with these regimens, they may result in comparable outcomes. Methods We conducted a single center, retrospective analysis of adult AML patients in CR1 or CR2 who underwent a first T-cell replete HLA-8/8 matched related or unrelated donor alloHCT. Patients received either parenteral Bu (12.8 mg/kg total over 4 days) with Cy (120 mg/kg total over 2 days) or parenteral Bu (400 mg/m2 total over 4 days) with Flu (160 mg/m2 total over 4 days). Bu dose adjustment was not used in either cohort. In addition to cytogenetic risk group stratification by European LeukemiaNet criteria (Döhner H, et al, Blood 2016), a subset of patients had a 36-gene somatic mutation panel assessed prior to alloHCT by next-generation sequencing. Pre-transplant characteristics were compared between regimens with Chi-square, Fisher's exact, or Wilcoxon rank sum tests. Differing characteristics were included in a multivariable Fine and Gray regression model with results as hazard ratios (HR) and 95% confidence intervals (CI). Results From 2008 - 2017, 76 AML patients receiving Bu/Cy and 50 receiving Bu/Flu were identified meeting inclusion criteria (Bu/Flu used starting in 2010). Median age at transplant was 51 (21-61) years for Bu/Cy vs. 64 (34-74) for Bu/Flu (P 〈 0.001). The cohorts were otherwise comparable in regards to gender, race, performance status, HCT-CI, and disease status at alloHCT. Bu/Cy vs. Bu/Flu patients had 16% vs. 10% favorable, 66% vs. 50% intermediate, and 18% vs. 40% adverse-risk cytogenetics (P=0.033). The most common somatic mutations in the Bu/Cy cohort were FLT3 (20%), NPM1 (18%), DNMT3A (16%), TET2 (9%), CEBPA (5%), and IDH1 (5%). In the Bu/Flu cohort, these were FLT3 (20%), NPM1 (18%), NRAS (12%), TET2 (12%), and DNMT3A (10%). There were no significant differences in somatic mutations between the cohorts, except for a higher incidence of NRAS in the Bu/Flu cohort (12% vs. 4%, P=0.029). Bu/Flu patients were more likely to have an unrelated donor (70% vs. 47%, P=0.012) and receive a peripheral blood stem cell (PBSC) graft (94% vs. 17%, P 〈 0.001). As such, Bu/Flu patients had more rapid neutrophil (median 13 vs. 14 days, P=0.009) and platelet (median 15 vs. 20 days, P 〈 0.001) recovery and a shorter length of hospital stay (LOS) (median 22 vs. 27 days, P 〈 0.001). In multivariable analysis, Bu/Flu patients trended towards more chronic graft-versus-host-disease (GvHD; any stage) (HR 0.42, CI 0.16-1.11, P=0.08), but there were no other differences in CMV infections, other infections, acute GvHD, relapse, relapse mortality (RM), non-relapse mortality (NRM), relapse-free (RFS), and overall survival (OS). 58% of Bu/Cy and 56% of Bu/Flu patients remain alive with median follow-up of 59 and 22 months, respectively (P=0.003). The most common causes of death for these respective cohorts were relapse (50% vs. 41%) and infection (16% vs. 27%). Conclusion Bu/Cy and Bu/Flu in alloHCT for AML results in comparable incidences of infection, GvHD, RM, NRM, RFS, and OS. This was despite Bu/Flu patients being older and more likely to have adverse cytogenetics and an unrelated donor. Bu/Flu is better tolerated with less toxicity. Faster hematopoietic recovery and shorter LOS with Bu/Flu reflects PBSC graft use and has implications for health care resource utilization. Future prospective studies with larger cohorts and cost-effectiveness analyses comparing these conditioning strategies are warranted. In this analysis, no mutations appeared to be sensitive to use of the more intensive regimen, Bu/Cy. Further investigation of pre-transplant or post-transplant persistence of somatic mutations may risk stratify those who may benefit from more intensive or innovative approaches to prevent relapse after transplant. Disclosures Gerds: Apexx Oncology: Consultancy; Celgene: Consultancy; CTI Biopharma: Consultancy; Incyte: Consultancy. Majhail:Incyte: Honoraria; Atara: Honoraria; Anthem, Inc.: Consultancy.

Abstract: Introduction: It has been shown that racial/ethnic minorities have worse survival after matched unrelated donor allogeneic hematopoietic cell transplantation(allo-HCT) compared to Whites. Whether the racial disparity in allo-HCT outcomes persists in long-term survivors, and possibly may even be exacerbated in this population that frequently transitions back from the transplant center to their local healthcare providers, is unknown. In the current study we sought to compare long-term outcomes among one-year survivors, by race/ethnicity and socioeconomic status (SES), after allo-HCT reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). Methods: The CIBMTR database was used to identify 5,473 patients with Acute Myeloid Leukemia (AML), Acute Lymphocytic Leukemia (ALL), Chronic Myeloid Leukemia (CML), or Myelodysplastic Syndrome (MDS) who received HCT between 2007-2017, who were alive and in remission for at least 1 year after allo-HCT. Study was restricted to patients transplanted in the United States. Cox regression model was used to determine association of ethnicity/race and SES with overall survival (OS), relapse, and treatment related mortality (TRM). Standardized mortality ratio (SMR) was calculated to compare mortality rates of the study patients to their general population peers matched on race/ethnicity, age and sex. Results: Patients were reported to be Non-Hispanic White (W) (n=4385), Non-Hispanic Black (B) (n=338), Hispanic (H) (n=516), and Asian (A) (n=234). Median follow up after 1 year allo-HCT (months): 69 W, 50 B, 59 H and 57 A (Table 1). Patient neighborhood poverty level was estimated from residential ZIP code at the time of allo-HCT. A ZIP code with ≥20% of persons below the federal poverty level was considered high poverty area. In multivariable analysis, we observed no significant differences in OS, relapse or TRM based on race or poverty level when adjusted for patient-, disease- and transplant-related covariates (Table 2). Conclusions: Our study highlights that among those who survived at least 1-year in remission after allo-HCT, previously reported disparities in post HCT outcomes based on racial/ethnic factors, are not evident in contemporary practice. This might suggest that previously recognized disparity in outcomes could be due to factors that mostly affect patients in their first year post HCT. Future studies are needed to identify these early adverse factors and implement strategies to mitigate them. Figure 1 Figure 1. Disclosures Blue: Janssen Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; WebMD: Consultancy. Wood: Pfizer: Research Funding; Teladoc: Consultancy; Koneksa Health: Consultancy, Current equity holder in publicly-traded company. Majhail: Incyte Corporation: Consultancy; Anthem, Inc: Consultancy. Saber: Govt. COI: Other.

Abstract: Introduction Umbilical cord blood (UCB) remains an important source of hematopoietic stem cells for patients, where no matched donor is available and for racial minorities. However, cord blood transplants have been associated with delayed hematopoietic recovery, prolonged hospitalization, and higher costs of transplant compared with other donor sources. Omidubicel is an advanced cell therapy that preserves stem cell function to optimize cell homing, engraftment, differentiation, and self-renewal and is manufactured from an appropriately HLA-matched single UCB unit for each patient. A recent phase III clinical trial (NCT02730299) reported that patients who received omidubicel experienced faster time to neutrophil engraftment, faster platelet recovery, reduced rates of infections and shorter hospitalization time than patients who received standard single (33%) or double (67%) UCB transplantation [Horwitz et al, Blood, 2021]. We report on an analysis of resource utilization including hospital length of stay, hospital care setting, visits by provider type, rates of transfusions and readmissions from the Phase III trial. Methods The Phase III clinical trial included patients aged 12-65 with hematological malignancies and eligible for an allogeneic transplant. The primary endpoint was time to neutrophil engraftment, with secondary endpoints of time to platelet engraftment, first grade 2/3 bacterial or fungal infections and days alive and out of hospital in the first 100 days. 125 patients were randomized in the study. We analyzed resource utilization data for patients treated with omidubicel (n=52) or UCB (n=56) ("as-treated population") focusing on resource utilization within the first 100 days of transplantation. Summary statistics were compared between treatment arms, means and medians used to draw comparison and significance testing was performed. Results In the Phase III clinical trial, omidubicel met its primary endpoint and secondary endpoints with statistical significance. The demographics and patient characteristics were overall well-balanced with slightly more males (52% vs 63%) and a lower median age (40 vs 36) in the UCB arm. The study population was diverse with 17.6% Black, 14.8% Asian, 14% Hispanic or Latino and 12% other/unknown. Most patients had AML (45%) or ALL (34.3%), with MDS, CML and lymphomas making up the rest of the study population. The disease risk index was high/very high in 35% of the patients and 24% of the patients had a Karnofsky/Lansky performance score of & lt;90. The rapid hematopoietic recovery was supported by a reduced rate of infections. The rates of acute and chronic GVHD in the two arms were comparable. Within the first 100 days after transplant, omidubicel patients experienced shorter average total length of hospital stay than UCB recipients (mean 41.2 vs 50.8 days; p = 0.027) and more days alive and out of the hospital (mean 55.8 vs 43.7 days; p=0.023). 12% of patients on omidubicel arm died vs 16% on UCB arm before day 100. During the primary hospitalization (transplant to discharge), fewer omidubicel patients required intensive care unit (ICU) stay (9.6% vs 23.2%) and spent fewer days in the ICU (mean 0.4 vs 4.7 days; p =0.028) and the transplant unit (mean 25.3 vs 32.9 days; p =0.022) compared to UCB recipients. Omidubicel patients required fewer outpatient consultant visits and fewer outpatient non-consultant visits (X-rays, scans, biopsies etc.) and required fewer platelet or other transfusions (RBC, albumin, plasma, and factor product) within 100 days from transplant (Table 1). Conclusions This analysis shows that more rapid hematopoietic recovery in patients transplanted with omidubicel was associated with significantly shorter hospital length of stay and reduced healthcare resource use compared to UCB in the clinical trial. Although economic data were not collected as part of the clinical trial, the costs of providing transplantation care during the first 100 days are likely lower with omidubicel compared to UCB in the real-world setting, as hospital stay, outpatient visits, and blood product transfusions are among the major drivers of costs during this time period. Figure 1 Figure 1. Disclosures Majhail: Incyte Corporation: Consultancy; Anthem, Inc: Consultancy. Manghani: Gamida Cell, Inc.: Current Employment; Tricida, Inc.: Ended employment in the past 24 months. Sivaraman: Incyte Corporation: Current equity holder in publicly-traded company, Ended employment in the past 24 months; Gamida Cell, Inc.: Current Employment. Galamidi-Cohen: Gamida Cell, Ltd: Current Employment. Maziarz: Bristol-Myers, Squibb/Celgene,, Intellia, Kite: Honoraria; CRISPR Therapeutics: Consultancy; Artiva Therapeutics: Consultancy; Intellia: Honoraria; Omeros: Research Funding; Athersys: Other: Data and Safety Monitoring Board, Patents & Royalties; Incyte Corporation: Consultancy, Honoraria; Novartis: Consultancy, Other: Data and Safety Monitoring board, Research Funding; Allovir: Consultancy, Research Funding; Vor Pharma: Other: Data and Safety Monitoring Board.

Abstract: Background: The curative potential of allogeneic transplant (alloHCT) in patients with acute lymphoblastic leukemia (ALL) is hampered by relapse; the major cause of treatment failure. Risk factors for relapse include measurable residual disease (MRD) before or after alloHCT, transplantation in second complete remission (CR) or beyond, and reduced intensity conditioning (RIC) regimens. In ALL patients, relapse rates range from 30% to 50%, with most relapses occurring within the first year after alloHCT. After relapse, options for disease control are limited, and consequently overall survival is poor. Post-alloHCT maintenance may reduce MRD, provide time for graft-versus-leukemia to develop, and ultimately decrease relapse rates and prolong leukemia-free-survival. Inotuzumab ozogamicin (INO) is an anti-CD22 monoclonal antibody bound to calicheamicin which has significant activity against relapsed ALL. INO gained regulatory approval for the treatment of relapsed/refractory ALL based on a randomized phase 3 trial that showed an overall CR rate of 81% in the INO arm as compared to 29% in the standard arm. With the hypothesis that low-dose INO will be safe and will reduce the relapse rates, we are conducting a phase I/II study using this approach as post-alloHCT maintenance therapy. Methods: Eligibility included patients aged 16-75 who have undergone alloHCT for CD22+ALL in complete remission, have a high risk for relapse after alloHCT (MRD before or after alloHCT, transplantation, in second complete remission (CR) or beyond, reduced intensity conditioning (RIC) regimen used, lymphoid blast crisis of chronic myeloid leukemia, or Ph-like ALL), have adequate graft and organ function, are between day 40 and 100 post-alloHCT, do not have active grade III/IV GVHD or any active GVHD of the liver, and have no history of VOD. The primary objective of this phase I clinical trial is to define a post-alloHCT maximum tolerated dose (MTD) of INO. Secondary objectives include describing the safety profile of INO post-alloHCT, determining the rate of veno-occlusive disease in this setting, evaluating non-relapse mortality (NRM), disease free survival (DFS) and overall survival (OS) at 1 year post-alloHCT and 1 year post-last dose INO, determining the incidence of myeloid toxicity and secondary graft failure, and determining if INO at these doses are effective at eradicating MRD in this cohort of patients. Pre-treatment tests include a bone marrow biopsy and aspirate to assess disease state and MRD. The trial design is a 3+3 model. The study treatment consists of a total of four 28-day cycles of INO starting at dose level 0 (0.3mg/m2) given on day 1. The first cycle must be initiated between day 40 and 100 after alloHCT. Dose limiting toxicities (DLT) include VOD, prolonged cytopenia (more than 28 days), and death. If there are no DLTs experienced in a cohort, patients are enrolled in the next highest dose level (Table 1). Patients are monitored with routine blood work during each cycle. At 1 year after alloHCT, patients are assessed by restaging bone marrow biopsy and aspirate. Patients are followed up to 12 months after the last dose of INO. Interim Analysis: As of July 27th, 2021, 17 patients have been treated with a median number of 3 cycles completed. Two patients went off treatment after 1 cycle of INO (patient choice, DLT(prolong thrombocytopenia)), two after 2 cycles due to cytopenia, and three went off treatment after 3 cycles of INO (patient choice (1), physician choice (2)). All continued to be followed for safety. We have completed 1-year post-alloHCT follow up on twelve patients. Eleven out of twelve patients were alive and in CR at 12 months from last dose of INO. One patient out of twelve died of recurrent disease at 12 months following last dose of INO. No patients experienced VOD. Significant side effects included thrombocytopenia and neutropenia. The percentage of any aGVHD is 59% and 0% grade III/IV aGVHD. The percentage of any cGVHD is 18%. Patient characteristics are described in Table 2. Conclusions: In the phase 1 portion of this study, INO at doses of 0.3, 0.4, 0.5 and 0.6mg/m2 was well tolerated. Thrombocytopenia may be the dose-limiting toxicity. The low observed rate of relapse, along with the safety profile, investigation of low-dose INO as maintenance therapy after alloHCT will be continued in a phase II trial. Figure 1 Figure 1. Disclosures Metheny: Incyte: Speakers Bureau; Pharmacosmos: Honoraria. Sobecks: CareDX: Membership on an entity's Board of Directors or advisory committees. Caimi: Kite Pharmaceuticals: Consultancy; Verastem: Consultancy; Genentech: Research Funding; ADC Theraputics: Consultancy, Research Funding; TG Therapeutics: Honoraria; Seattle Genetics: Consultancy; XaTek: Patents & Royalties: Royalties from patents (wife); Amgen Therapeutics.: Consultancy. Majhail: Incyte Corporation: Consultancy; Anthem, Inc: Consultancy. Boughan: Beigene: Speakers Bureau. Malek: BMS: Honoraria, Research Funding; Amgen: Honoraria; Cumberland Inc.: Research Funding; Medpacto Inc.: Research Funding; Janssen: Other: Advisory board ; Takeda: Honoraria; Bluespark Inc.: Research Funding; Sanofi: Other: Advisory Board. Gerds: CTI BioPharma: Research Funding; Sierra Oncology: Consultancy; AbbVie: Consultancy; Celgene/Bristol Myers Squibb: Consultancy; Constellation: Consultancy; PharmaEssentia Corporation: Consultancy; Novartis: Consultancy. Hamilton: Syndax: Membership on an entity's Board of Directors or advisory committees; Equilium: Membership on an entity's Board of Directors or advisory committees. Giralt: CELGENE: Membership on an entity's Board of Directors or advisory committees; Actinnum: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; JAZZ: Membership on an entity's Board of Directors or advisory committees; JENSENN: Membership on an entity's Board of Directors or advisory committees; PFIZER: Membership on an entity's Board of Directors or advisory committees; AMGEN: Membership on an entity's Board of Directors or advisory committees; SANOFI: Membership on an entity's Board of Directors or advisory committees. de Lima: BMS: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Miltenyi Biotec: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Post- allogeneic transplant maintenance of inotuzumab for patients with ALL

Abstract: Background: The use of HCT to treat older (≥60 years) patients with hematological malignancies has markedly increased in recent years, however, the long-term effects of HCT on distress, psychosocial functioning, and HQOL in older HCT survivors is largely unknown. Though older HCT survivors have a higher risk of disease recurrence, they may have less access to resources and subsequently experience more pronounced late effects of disease and treatment. Confidence in Survivorship Information (CSI) in this specific age group has not been reported. Methods: We conducted a secondary analysis on a subgroup of patients enrolled in INSPIRE (NCT01602211) and PCORI-SCP (NCT02200133) clinical trials. Eligibility criteria for inclusion include HCT patients who were ≥ 60 years at time of transplant performed in 2003-2014, survived ≥ 1 year post-transplant with no evidence of disease relapse or secondary cancers. Patients were eligible for inclusion irrespective of transplant type (autologous or allogeneic), diagnosis, donor source or conditioning regimen. Primary endpoint was distress level in older HCT survivors; secondary endpoints included CSI and HQOL outcomes. We collected baseline distress level as measured by Cancer and Treatment Distress (CTXD) score, HQOL (measured by SF-12 Mental and Physical Component Summaries (PCS/MCS) and CSI (measured by a 15-item CSI questionnaire). Sociodemographic, disease and transplant factors were extracted from medical databases. Nonparametric (Wilcoxon rank sum/Kruskal-Wallis) test was conducted for comparing 2 or 3 groups. Spearman correlation and univariate linear regression model were used to evaluate associations between CTXD/CSI and PCS/MCS. Bonferroni correlation was used to adjust for multiple pairwise comparisons within age group. Results: A total of 567 patients satisfied the eligibility criteria and were included in this analysis. Median age at time of HCT was 69 years with 57% male; two-thirds were autologous HCT recipients. Table 1 details patient characteristics. The median CTXD score for older HCT survivors was 0.7 (range 0-2.7, SD 0.6) indicating low/insignificant level of distress post-HCT. 20-30% of HCT survivors reported moderate distress when asked about concerns regarding relapse risk, loss of energy and functional decline. Type of transplant (auto vs allo), age group ( & lt;65 years, 65-70 years, ≥70 years), and time from HCT (≤2 years vs & gt; 2 years) showed no apparent effect on reported distress level. CSI median score was 1.4 (range 0-2) which remains consistent with the score reported previously by the original trial including all age groups, indicating that older HCT survivors may have similar level of confidence in their survivorship information as their younger counterparts. Of note, close to 20% of the older HCT survivors reported poor CSI when asked about strategies for prevention and treatment of long-term effects of HCT and when asked about their confidence in availability of community resources to deal with long-term HCT complications. No statistically significant correlation was identified between CSI in older survivors and transplant type, time from HCT, or age group. HQOL outcomes indicated a median PCS of 48.2 (range 21.1 - 62.9) and a median MCS of 54.7 (range of 14.9 - 67.2). Interestingly, even though not reflected on the overall median CTXD and CSI scores for this cohort, a significant individual association between CTXD/CSI and PCS/MCS measures of HQOL was found (Figure 1). A subgroup analysis conducted on older alloHCT recipients confirmed the same findings of clinically insignificant distress level (mean CTXD ≤1.1) while having a similar level of CSI when compared to all age groups. Interestingly, time from HCT (≤2 years vs & gt; 2 years) showed no significant effect on distress level reported by older alloHCT survivors, and cGVHD status did not correlate with CTXD or CSI scores nor with PCS/MCS in older alloHCT survivors. Conclusion: This is the largest study to date to investigate patient-reported distress, CSI and HQOL in older HCT survivors. Our data indicate that older HCT survivors have low levels of stress after HCT and had confidence in survivorship information in most aspects of their care. However, targeted interventions should focus on improving strategies for prevention, treatment and availability of community resources to deal with late effects of HCT; aspects reported as points of low CSI by older HCT survivors. Figure 1 Figure 1. Disclosures Farhadfar: Incyte: Consultancy. Shaw: Orca bio: Consultancy; mallinkrodt: Other: payments. Devine: Be the Match: Current Employment; Orca Bio: Consultancy, Research Funding; Johnsonand Johnson: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding; Magenta Therapeutics: Current Employment, Research Funding; Tmunity: Current Employment, Research Funding; Vor Bio: Research Funding; Kiadis: Consultancy, Research Funding. Majhail: Anthem, Inc: Consultancy; Incyte Corporation: Consultancy. Wingard: Merck: Consultancy; AlloVir: Consultancy; Celgene: Consultancy; Shire: Consultancy; Janssen: Consultancy; Cidara Therapeutics: Consultancy.