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Background Magrolimab (previously named 5F9) is a first-in-class antibody targeting CD47, a macrophage immune checkpoint and "don't eat me" signal on cancers. CD47 blockade induces tumor phagocytosis and eliminates leukemia stem cells (LSC) in AML models. Azacitidine (AZA) synergizes with magrolimab by inducing "eat me" signals on AML, to enhance phagocytosis. A Phase 1b trial of magrolimab+AZA was initiated in MDS/AML patients with preliminary reported results mainly from the safety cohort demonstrating high response rates in both diseases. Here we report data from the expansion cohort of this ongoing trial. Methods Results from this Phase 1b reported here focus on treatment of magrolimab+AZA in untreated intermediate to very high risk MDS patients by IPSS-R and untreated AML (induction chemotherapy ineligible) patients. A magrolimab priming/intrapatient dose escalation regimen (1-30 mg/kg weekly) was utilized to mitigate on target anemia. AZA dosing was 75mg/m2 days 1-7 on a 28 day cycle. Responses were assessed by IWG 2006 and ELN 2017 criteria for MDS and AML patients, respectively. Results 43 patients (18 MDS and 25 AML) with a median of 73 years of age were treated with magrolimab+AZA. 19% were intermediate cytogenetic risk with 63% poor risk (19% unknown). 28% of patients harbored a TP53 mutation. Magrolimab+AZA was well-tolerated with a safety profile similar to AZA monotherapy. Treatment-related AEs (>15% of patients) for magrolimab+AZA were anemia (37%), neutropenia (26%), and thrombocytopenia (26%). Treatment-related febrile neutropenia occurred in only 1 (2%) patient. Only 1 patient discontinued due to an AE. 29 patients were evaluable for efficacy at time of data cut. 13/13 (100%) untreated MDS patients had an objective response with 7 patients (54%) achieving a CR, 5 (39%) with marrow CR (3/5 also had hematologic improvement (HI)), and 1 (7%) with HI alone. In AML, 11/16 (69%) had an objective response; 8/16 (50%) with CR or CRi, 2 (13%) with PR, 1 (6%) with MLFS, and 5 (31%) with stable disease. Time to response was more rapid (median 1.9 mos) than expected for AZA alone. For those with abnormal cytogenetics at baseline, 40% and 44% of MDS and AML patients achieved a cytogenetic CR, respectively. 4/8 (50%) AML patients with CR/CRi and 2/12 (17%) MDS patients with CR or marrow CR were MRD negative by flow cytometry. 11/16 (69%) AML patients became RBC transfusion independent and 11/13 (85%) MDS patients had hematologic improvement. Given that CD47 is an LSC marker on leukemic cells, CD34+CD38- putative LSC frequency was measured by flow cytometry in the bone marrow in 5F9+AZA treated AML/MDS patients. In data available for analysis, LSCs were completely eliminated in 10/16 (63%) of AML/MDS patients who had a clinical response. Lastly, mutational analyses are ongoing to correlate subgroups with response. Interestingly, 7/8 (88%) evaluable TP53 mutant patients (5/6 AML patients [5 CR/CRi], 2/2 MDS [1 CR, 1 marrow CR]) achieved an objective response, highlighting efficacy in a poor prognosis and therapy-refractory population. No median duration response or overall survival has been reached for either MDS or AML patients with a median follow-up of 4.9 months (range 3.1 - 8.8 months) for MDS and 5.8 months (range 1.9 - 9.5 months) for AML. Conclusions Magrolimab+AZA is a novel immunotherapy regimen that blocks a key macrophage checkpoint. The combination therapy continues to be well tolerated with robust activity in MDS and AML patients with an ORR of 100% and 69%, respectively. High rates of putative LSC eradication suggest potential durable responses, with no median duration of response yet reached. Initial data indicate that 5F9+AZA may be particularly effective in TP53 mutant patients, a treatment-refractory subgroup. Expansion cohorts are ongoing (NCT03248479) with registrational studies in MDS being initiated. Additional patients, follow-up, and mutational characterization will be reported at time of presentation. Funded by Forty Seven and the California Institute for Regenerative Medicine. Disclosures Sallman: Celyad: Membership on an entity's Board of Directors or advisory committees. Lee:Bayer: Research Funding; Roche: Research Funding; Abbvie: Research Funding; Forty Seven, Inc.: Research Funding; Tolero: Research Funding. Daver:Immunogen: Consultancy, Research Funding; Forty-Seven: Consultancy; Agios: Consultancy; Pfizer: Consultancy, Research Funding; Servier: Research Funding; Hanmi Pharm Co., Ltd.: Research Funding; Karyopharm: Consultancy, Research Funding; Jazz: Consultancy; Otsuka: Consultancy; Celgene: Consultancy; NOHLA: Research Funding; Astellas: Consultancy; Novartis: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Sunesis: Consultancy, Research Funding; Glycomimetics: Research Funding. Garcia-Manero:Amphivena: Consultancy, Research Funding; Helsinn: Research Funding; Novartis: Research Funding; AbbVie: Research Funding; Celgene: Consultancy, Research Funding; Astex: Consultancy, Research Funding; Onconova: Research Funding; H3 Biomedicine: Research Funding; Merck: Research Funding. Komrokji:Novartis: Speakers Bureau; Incyte: Consultancy; JAZZ: Consultancy; Agios: Consultancy; DSI: Consultancy; pfizer: Consultancy; celgene: Consultancy; JAZZ: Speakers Bureau. Van Elk:Forty Seven, Inc.: Employment, Equity Ownership. Lin:Forty Seven, Inc.: Employment, Equity Ownership. Takimoto:Forty Seven, Inc.: Employment, Equity Ownership, Patents & Royalties. Chao:Forty Seven, Inc.: Employment, Equity Ownership, Patents & Royalties. Vyas:Novartis: Research Funding, Speakers Bureau; Celgene: Research Funding, Speakers Bureau; Pfizer: Speakers Bureau; Forty Seven, Inc.: Research Funding; Daiichi Sankyo: Speakers Bureau; Abbvie: Speakers Bureau; Astellas: Speakers Bureau.

Key Points• The effect of donor age on survival is negated by the effect of patient age.• Survival did not differ between sibling and offspring donor transplantation.We studied the association between non-HLA donor characteristics (age, sex, donor- Two-year survival adjusted for CMV seropositivity, disease, and disease risk index was lower in patients aged 55 to 78 years after transplantation of grafts from donors younger than 30 years (53%) or aged at least 30 years (46%) compared with younger patients who received grafts from donors younger than 30 years (61%) and at least 30 years (60%; P , .0001).Similarly, 2-year survival in patients aged 55 to 78 years was lower after transplantation of grafts from siblings (45%) or offspring (48%) compared with patients aged 18 to 54 years after transplantation of grafts from siblings (62%), offspring (58%), and parents (61%; P , .0001). Graft failure was higher after transplantation of grafts from parents (14%) compared with siblings (6%) or offspring (7%; P 5 .02). Other non-HLA donor characteristics were not associated with survival or graft failure. The current analyses suggest patient and disease, rather than non-HLA donor characteristics, predominantly influence survival in adults.

The number of HLA-haploidentical hematopoietic cell transplants continues to increase worldwide due to recent improvements in outcomes, allowing more patients with hematological malignancies and non-malignant disorders to benefit from this procedure and have a chance to cure their disease. Despite these encouraging results, questions remain as multiple donors are usually available for transplantation, and choosing the best HLA-haploidentical donor for transplantation remains a challenge. Several approaches to haploidentical transplantation have been developed over time and, based on the graft received, can be grouped as follows: T-cell depleted haploidentical transplants, either complete or partial, or with T-cell replete grafts, performed with post-transplant cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis, or G-CSF-primed bone marrow graft and enhanced GVHD prophylaxis. Carefully selecting the donor can help optimize transplant outcomes for recipients of haploidentical donor transplants. Variables usually considered in the donor selection include presence of donor-specific antibodies in the recipient, donor age, donor/recipient gender and ABO combinations, and immunogenic variables, such as natural killer cell alloreactivity or KIR haplotype.Here we provide a comprehensive review of available evidence for selecting haploidentical donors for transplantation, and summarize the recommendations from the European Society for Blood and Marrow Transplantation (EBMT) on donor selection for different transplant platforms.

Key Points The incidence of IFIs during VEN-HMA therapy is low, and the used antifungal prophylaxis approach did not influence the risk of IFIs. The risk of IFIs is higher in nonresponders and those who were treated in the r/r AML setting.

Background : The safety and efficacy of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emergency-use authorized (EUA) vaccines has been confirmed in general population. However, there is no data on its safety/tolerability or efficacy in recipients of allogeneic hematopoietic stem cell transplant (HCT). Objectives : We performed this study to identify the incidence of adverse events following SARS-CoV2 EUA vaccines and the incidence of new onset GVHD or worsening of existing GVHD after EUA vaccine administration and the incidence SAR-CoV2 positivity in vaccinated HCT patients. Study Design : We retrospectively reviewed 113 HCT patients who received at least one dose of EUA vaccine to describe the safety/tolerability, any impact on graft-versus-host disease (GVHD), and incidence of SARS-CoV2 PCR positivity after vaccination. Patients received either Pfizer (BNT162b2) or Moderna (mRNA-1273) vaccines. Patients were included if they were 18 years or older and received at least one dose of vaccine in the post HCT setting. Results : Most patients presented with myalgias/arthralgias (first dose 7.7%, second dose 14.6%), fatigue (first dose 15.4%, second dose 29.2%), and injection site pain (first dose 40.4%, second dose 43.8%). Other side effects experienced by patients included: nausea, vomiting, diarrhea, headache, injection-site rash and swelling. Liver function abnormalities occurred in 18.6% of patients. The incidence of neutropenia, thrombocytopenia, and lymphopenia occurred at 13.3%, 11.5%, and 8.8% respectively. Forty percent of patients who had active chronic GVHD at the time of vaccination where worsening chronic GVHD occurred in 3.5% of patients. New chronic GVHD developed in 9.7% of patients after vaccination. Conclusion : In conclusion, the SARS-CoV2 EUA vaccines were well-tolerated in allogeneic HCT recipients.

Therapy-related acute lymphoblastic leukemia remains poorly defined due to a lack of large data sets recognizing the defining characteristics of this entity. We reviewed all consecutive cases of adult acute lymphoblastic leukemia treated at our institution between 2000 and 2017 and identified therapy-related cases - defined as acute lymphoblastic leukemia preceded by prior exposure to cytotoxic chemotherapy and/or radiation. Of 1022 patients with acute lymphoblastic leukemia, 93 (9.1%) were classified as therapy-related. The median latency for therapy-related acute lymphoblastic leukemia onset was 6.8 years from original diagnosis, and this was shorter for patients carrying the MLL gene rearrangement compared to those with other cytogenetics. When compared to de novo acute lymphoblastic leukemia, therapy-related patients were older (P<0.01), more often female (P<0.01), and had more MLL gene rearrangement (P<0.0001) and chromosomes 5/7 aberrations (P=0.02). Although therapy-related acute lymphoblastic leukemia was associated with inferior 2-year overall survival compared to de novo cases (46.0% vs. 68.1%, P=0.001), prior exposure to cytotoxic therapy (therapy-related) did not independently impact survival in multivariate analysis (HR=1.32; 95% CI: 0.97–1.80, P=0.08). There was no survival difference (2-year = 53.4% vs. 58.9%, P=0.68) between the two groups in patients who received allogenic hematopoietic cell transplantation. In conclusion, therapy-related acute lymphoblastic leukemia represents a significant proportion of adult acute lymphoblastic leukemia diagnoses, and a subset of cases carry clinical and cytogenetic abnormalities similar to therapy-related myeloid neoplasms. Although survival of therapy-related acute lymphoblastic leukemia was inferior to de novo cases, allogeneic hematopoietic cell transplantation outcomes were comparable for the two entities.

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