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Introduction: Myeloid malignancies are a heterogeneous group of clonal bone marrow disorders that are complex to manage in the community and therefore often referred to subspecialists at tertiary oncology referral centers. Many patients do not live in close proximity to tertiary referral centers and are unable to commute long distances due to age, comorbidities, and frailty. Interventions that minimize the travel time burden without compromising quality of care are an area of unmet need. We describe a cancer care delivery model for patients with myeloid malignancies that is built around telehealth and enables this vulnerable population access to care at an NCI-designated cancer center while receiving majority of their care close to home. Methods and Materials: We report on a cohort of patients with myeloid malignancies who were co-managed by a general community oncologist and an academic leukemia subspecialist at Montefiore Einstein Cancer Center in New York. Patients were initially referred to our institute for a second opinion by community practices that are in partnership with Montefiore Health System, and initial visits were in-person or via telehealth. Treatment plans were made after discussion with patient’s local community oncologist. Patients then continued to receive majority of their treatment and supportive care including transfusion support with their local oncologist, and follow-up visits were mainly via telehealth with the academic leukemia subspecialist. Results: Our cohort of 12 patients had a median age of 81 years (range, 59–88 years). Patients remained on active treatment for a median time of 357 days (range, 154–557 days). Most of our patients had a performance status of ECOG 2 or higher. Three patients had myelodysplastic syndromes, 7 patients had acute myeloid leukemia, and 2 patients had myelofibrosis. The median number of hospitalizations over the total treatment time period was one. Conclusion: We demonstrate a shared academic and community care co-management model for the treatment of myeloid malignancies in elderly, frail patients using telehealth as a backbone with a very low hospitalization rate.

Purpose: Thrombocytopenia is a serious complication of myelodysplastic syndromes (MDS) associated with an increased bleeding risk and worse prognosis. Eltrombopag (ELT), a thrombopoietin receptor agonist, can increase platelet counts and reverse anti-megakaryopoietic effects of lenalidomide (LEN) in preclinical studies. We hypothesized ELT would reduce the incidence of thrombocytopenia in MDS. Patients and Methods: We conducted a Phase II multicenter trial of ELT and LEN in adult patients with low- or intermediate-1–risk MDS with symptomatic or transfusion-dependent anemia or thrombocytopenia (NCT01772420). Thrombocytopenic patients were started on ELT and subsequently treated with LEN after platelets were increased. Patients without thrombocytopenia were started on LEN monotherapy and treated with ELT if they became thrombocytopenic. Results: Fifty-two patients were enrolled; mean age was 71 years (range 34–93). Overall response rate (ORR) in the intention-to-treat population was 35% (18/52). ELT monotherapy led to ORR of 33.3% (7/21), 29% achieving hematologic improvement (HI)-Platelets, and 24% bilineage responses. LEN monotherapy had 38% ORR (6/16) with all responders achieving HI-Erythroid. Fifteen patients received both ELT and LEN with ORR of 33.3%, 20% achieved HI-Erythroid, and 20% HI-Platelets with 13% bilineage responses. Median duration of response was 40 weeks for ELT (range 8–ongoing), 41 weeks (25–ongoing) for LEN, and 88 weeks (8.3–ongoing) for ELT/LEN. Non-hematologic grade 3–4 treatment-related adverse events were infrequent. Among patients on ELT, 2 had major bleeding events, 1 had a reversible increase in peripheral blasts, and 1 developed marrow fibrosis after 6 years on ELT. Conclusions: ELT and LEN are well tolerated and effective in achieving hematologic improvement in patients with low-/intermediate-risk MDS.

Supplemental Figure 1. Overall Survival Responders vs Non-Responders Supplemental Figure 2. Overall Survival Among Groups

Purpose:Thrombocytopenia is a serious complication of myelodysplastic syndromes (MDS) associated with an increased bleeding risk and worse prognosis. Eltrombopag (ELT), a thrombopoietin receptor agonist, can increase platelet counts and reverse anti-megakaryopoietic effects of lenalidomide (LEN) in preclinical studies. We hypothesized ELT would reduce the incidence of thrombocytopenia in MDS.Patients and Methods:We conducted a Phase II multicenter trial of ELT and LEN in adult patients with low- or intermediate-1–risk MDS with symptomatic or transfusion-dependent anemia or thrombocytopenia (NCT01772420). Thrombocytopenic patients were started on ELT and subsequently treated with LEN after platelets were increased. Patients without thrombocytopenia were started on LEN monotherapy and treated with ELT if they became thrombocytopenic.Results:Fifty-two patients were enrolled; mean age was 71 years (range 34–93). Overall response rate (ORR) in the intention-to-treat population was 35% (18/52). ELT monotherapy led to ORR of 33.3% (7/21), 29% achieving hematologic improvement (HI)-Platelets, and 24% bilineage responses. LEN monotherapy had 38% ORR (6/16) with all responders achieving HI-Erythroid. Fifteen patients received both ELT and LEN with ORR of 33.3%, 20% achieved HI-Erythroid, and 20% HI-Platelets with 13% bilineage responses. Median duration of response was 40 weeks for ELT (range 8–ongoing), 41 weeks (25–ongoing) for LEN, and 88 weeks (8.3–ongoing) for ELT/LEN. Non-hematologic grade 3–4 treatment-related adverse events were infrequent. Among patients on ELT, 2 had major bleeding events, 1 had a reversible increase in peripheral blasts, and 1 developed marrow fibrosis after 6 years on ELT.Conclusions:ELT and LEN are well tolerated and effective in achieving hematologic improvement in patients with low-/intermediate-risk MDS.

Adult T-cell leukemia/lymphoma (ATLL) remains challenging to treat and has dismal outcome. Allogeneic stem-cell transplantation (allo-SCT) has promising results, but data remain scarce. In this single-center retrospective analysis of 100 patients with ATLL from north America (67 acute, 22 lymphomatous), 17 underwent allo-SCT and 5 autologous SCT (ASCT), with a median follow-up of 65 months. Post-transplant 3-years relapse incidence (RI) and non-relapse mortality (NRM) were 51% and 37%, respectively, and 3-year progression-free survival (PFS) and overall survival (OS) were 31% and 35%, respectively. ASCT 1-year RI was 80% compared to 30% in allo-SCT (p = 0.03). After adjusting for immortal-time bias, allo-SCT had significantly improved OS (HR = 0.4, p = 0.01). In exploratory multivariate analysis, patients achieving first complete response and Karnofsky score ≥ 90 had significantly better outcomes, as did Black patients, compared to Hispanics, who had worse outcome. In transplanted patients, 14 died within 2 years, 4 of which ASCT recipients. Our data are the largest ATLL transplant cohort presented to date outside of Japan and Europe. We show that allo-SCT, but not ASCT, is a valid option in select ATLL patients, and can induce long term survival, with 40% of patients alive after more than 5 years.

Thrombocytopenia is a serious complication of MDS associated with an increased bleeding risk and worse prognosis. Eltrombopag (ELT), a thrombopoietin receptor agonist, can increase platelet counts and reverse anti-megakaryopoietic effects of lenalidomide (LEN) in preclinical studies. We hypothesized ELT would reduce the incidence of thrombocytopenia in MDS.We conducted a phase 2 multicenter trial of ELT and LEN in adult patients with low or intermediate-1-risk MDS with symptomatic or transfusion-dependent anemia or thrombocytopenia (NCT01772420). Thrombocytopenic patients were started on ELT and subsequently treated with LEN after platelets were increased. Patients without thrombocytopenia were started on LEN monotherapy and treated with ELT if they became thrombocytopenic.52 patients were enrolled; mean age was 71 years (range 34-93). ORR in the ITT population was 35% (18/52). ELT monotherapy led to ORR of 33.3% (7/21), 29% achieving HI-Platelets, and 24% bilineage responses. LEN monotherapy had 38% ORR (6/16) with all responders achieving HI-Erythroid. 15 patients received both ELT and LEN with ORR of 33.3%, 20% achieved HI-Erythroid, and 20% HI-Platelets with 13% bilineage responses. Median duration of response was 40 weeks for ELT (range 8-ongoing), 41 weeks (25-ongoing) for LEN, and 88 weeks (8.3-ongoing) for ELT/LEN. Non-hematological grade 3-4 treatment-related adverse events were infrequent. Among patients on ELT, 2 had major bleeding events, 1 had a reversible increase in peripheral blasts, and 1 developed marrow fibrosis after 6 years on ELT.ELT and LEN are well tolerated and effective in achieving hematological improvement in patients with low/intermediate-risk MDS.

It is well established that COVID-19 carries a higher risk of morbidity and mortality in patients with hematologic malignancies, however, very little data on ethnicity specific responses in this particular patient population currently exist. We established a program of rapid vaccination and evaluation of antibody-mediated response to all EUA COVID-19 vaccines in an inner city minority population to determine the factors that contribute to the poor seroconversion to COVID-19 vaccination in this population. We conducted a cross-sectional cohort study of 126 patients with hematologic malignancies in the outpatient practices of our institution who completed their vaccination series with one of the three FDA EUA COVID-19 vaccines, Moderna, Pfizer, or Johnson & Johnson (J&J). We qualitatively measured Spike IgG production in all patients using the AdviseDx SARS-CoV-2 IgG II assay and quantitatively in 106 patients who completed their vaccination series with at least 14 days after the 2nddose of the Moderna or Pfizer vaccines or 28d after the single J&J vaccine. Patient characteristics were analyzed using standard descriptive statistics and associations between patient characteristics, cancer subtypes, treatments, and vaccine response were assessed using Fisher Exact test or Kruskal-Wallis Rank Sum test. The majority of patients (74%) were minorities. Seventy patients (60%) received Pfizer, 36 patients (31%) Moderna, and 10 patients (9%) J&J. We observed a high-rate of seropositivity (86%) with 16 pts (14%) having a negative Spike IgG. Of the 86 minority patients included, 94% Blacks (30/32) and 87% (39/45) Hispanics showed seropositivity. The factors that contributed to significantly lower seroconversion rates included patients with Non-Hodgkin lymphoma (p=0.005), those who received cytotoxic chemotherapy (p=0.002), IVIG (p=0.01), CAR-T cell therapy (p=0.00002), and CD20 monoclonal antibodies (Ab) (p=0.0000008). Plasma cell neoplasms (p=0.02), immunomodulatory agents (p=0.01), and proteasome inhibitors (p=0.01) had significantly higher seroconversion rates, and those with a history of prior COVID-19 (11%, 12/106) had significantly higher antibody titers (p=0.0003). The positivity rate was 86% (37 seropositive, 6 seronegative) for autologous HSCT and 75% (3 seropositive, 1 seronegative) for allogeneic HSCT. No life-threatening AE were observed. We show high seroconversion rates after SARS-CoV-2 vaccination in non-White patients with hematologic malignancies treated with a wide spectrum of therapeutic modalities. Vaccination is safe, effective, and should be encouraged in most patients with hematologic malignancies. Our minorities based study could be employed as an educational tool to dispel myths and provide data driven evidence to overcome vaccine hesitancy.

Adult T-cell leukemia/lymphoma (ATLL) is a rare, human T-cell lymphotropic virus 1 (HTLV-1)-driven malignancy with treatment challenges and a dismal prognosis. Allogeneic stem cell transplant (alloSCT) has shown encouraging outcomes, especially long-term survival, for ATLL patients, but data are sparse and mostly limited to Japanese patients. This is the largest experience studying the feasibility of stem cell haploidentical donors, which will greatly improve donor transplantation in ATLL outside Japan/Europe.Comparing the outcomes of ATLL patients who underwent either autologous SCT (ASCT) or alloSCT and studying factors affecting transplant outcomes.Retrospective study including patients transplanted between 2005 and 2020; median follow-up of 41 months.Tertiary oncologic center.With 116 patients, this was one of the largest ATLL cohorts in the USA; 21 patients were transplanted with 16 alloSCTs and 5 ASCTs (43% female; median age 56 years [range 39-74]; 67% Black and 29% Hispanic).Chart review.The 3-year relapse incidence (RI) and non-relapse mortality (NRM) were 54% and 39%, respectively, and 3-year progression-free survival (PFS) and overall survival (OS) were 27% and 35%, respectively.Four out of 5 patients relapsed after ASCT, with 3 dying from disease progression and 1 lost to follow-up; 1-year RI was 80% versus 32% in alloSCT (P=0.045). In exploratory multivariate analysis, patients achieving first complete response and with good baseline performance scores had significantly better outcomes compared to their counterparts regardless of transplant type. Hispanic patients had worse outcomes, including NRM, PFS, and OS, with OS HR of 7; P=0.04. Thirteen patients died within 2 years, 3 of whom were ASCT recipients: 8 from relapse/progression, including the 3 ASCT patients, and 4 from transplant-related toxicities.AlloSCT led to better long-term outcomes and lower relapse rates than ASCT. Haploidentical and HTLV-1-positive donors are feasible in the absence of suitable donors. Interestingly, Hispanic patients had worse outcomes compared to Black patients in the multivariate analysis. To our knowledge, this has not been previously described and could possibly be attributed to epidemiologic genetic variations in HTLV-1 subtypes between the 2 groups. Further investigation is required, including genomic profiling of these patients.

Introduction Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of B- cell malignancies leading to durable responses in patients with relapsed/refractory disease. 1,2 One of the most severe toxicities associated with this treatment is immune effector cell-associated neurotoxicity syndrome (ICANS), which was seen in 65-75% of patients treated with axicabtagene ciloleucel (axi-cel) in initial clinical trials. ICANS can range from mild headache to coma, and can occur with or without cytokine release syndrome (CRS). Due to the recent development of CAR T-cell therapy, the long-term effects of ICANS are unknown. This study sought to determine the long-term outcomes in patients with neurotoxicity from axi-cel. Methods We conducted a retrospective chart review of patients who received CAR T-cell therapy with axi-cel between June 2018 and June 2021. Neurotoxicity was graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) ICANS grading system. 3 The primary outcome was percentage of patients who had neurotoxicity defined as ICANS grade ≥ 1 as well as the percentage of patients with neurotoxicity lasting ≥ 1 month. We captured descriptive data such as age, sex, ethnicity, comorbidities, IPI score, stage, baseline neurologic dysfunction, performance status, and number of prior treatments. Secondary outcomes included progression free survival (PFS) and overall survival (OS). Results Thirty-four patients received axi-cel between June 2018 and June 2021 at our institution. Median age of patients was 65. Twenty patients (59%) were male and 14 (41%) were female. The majority of patients received axi-cel for diffuse large B-cell lymphoma (97%). Study population was predominantly hispanic (35%), white (32%), African american (29%) and asian (3%). (Sixteen patients (47%) developed neurotoxicity of any grade, with 7 patients (21%) ≥ grade 3. Of note, 4 patients (12%) died during admission for CAR T-cell therapy and 3/4 deaths were in patients with ICANS ≥ grade 3. Median follow up time was 8 months. Of the 12 patients with neurotoxicity who survived initial admission for CAR-T, 9 (75%) patients recovered from neurotoxicity and mental status was at baseline at discharge without recurrence during follow up. Three (25%) of patients had prolonged neurotoxicity lasting > 1 month. Long-term neurotoxicity included confusion, disorientation, and mild cognitive impairment in the three patients. One patient recovered 15 months after CAR T-cell infusion. 2 patients had prolonged neurotoxicity resulting in deterioration of functional status and death in 1 patient, and 1 patient transitioning to hospice and being lost to follow up. Conclusions Neurotoxicity from axicabtagene ciloleucel is a common adverse event, with half of patients in our cohort having neurotoxicity of some degree, and 20% ≥ grade 3. Twenty-five percent of patients that developed neurotoxicity had long-term effects lasting > 1 month, which resulted in deterioration of functional status in 2 patients. Long-term neurotoxicity included disorientation, confusion, and memory impairment. Our study is limited by a small sample size. Larger studies with longer follow-up times are needed to further characterize the long-term outcomes of neurotoxicity associated with CAR T-cell therapy. Neurotoxicity can be confounded by other causes of neurological dysfunction in these patients such as hospital delirium, chemotherapy toxicity, encephalopathy from infection, and subtle baseline neurologic dysfunction that may not be apparent at presentation. Next steps include prospective evaluation of patients with formal neurology evaluation prior to CAR T-cell therapy and periodically after treatment, in order to objectively monitor late neurologic effects of CAR T-cell therapy. 1. Fl, L. et al. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol. 20, (2019). 2. Jacobson, C. Primary Analysis of Zuma-5: A Phase 2 Study of Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed/Refractory (R/R) Indolent Non-Hodgkin Lymphoma (iNHL). in (ASH, 2020). 3. Dw, L. et al. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biol. Blood Marrow Transplant. J. Am. Soc. Blood Marrow Transplant. 25, (2019). Disclosures Gritsman: iOnctura: Research Funding. Shastri: Onclive: Honoraria; Guidepoint: Consultancy; GLC: Consultancy; Kymera Therapeutics: Research Funding. Verma: Celgene: Consultancy; BMS: Research Funding; Stelexis: Current equity holder in publicly-traded company; Curis: Research Funding; Eli Lilly: Research Funding; Medpacto: Research Funding; Novartis: Consultancy; Acceleron: Consultancy; Stelexis: Consultancy, Current equity holder in publicly-traded company; Incyte: Research Funding; GSK: Research Funding; Throws Exception: Current equity holder in publicly-traded company.

Background Globally, 5 million to 10 million people are infected with human T-cell leukemia virus type 1, which causes adult T-cell leukemia/lymphoma (ATLL) in 2% to 5% of the carriers. ATLL is a rare but extremely aggressive malignancy that can be challenging to diagnose. Very little data exist on the incidence patterns of ATLL in the United States. Methods ATLL cases reported to the National Program of Cancer Registries, the Surveillance, Epidemiology, and End Results (SEER) program, and the New York State Cancer Registry were used for the study. Age-adjusted incidence rates were calculated by age, race/ethnicity, sex, and year of diagnosis. The 5-year survival rate was compared among race/ethnicity groups with the SEER data. Results During 2001-2015, 2148 ATLL cases were diagnosed in the United States, 18% of which were in New York State. New York State had the highest incidence rate for ATLL, with a rising trend especially among non-Hispanic blacks (NHBs), whereas the incidence was stable across the remainder of the United States. NHBs were diagnosed at a younger median age (54 years) and had a shorter overall survival (6 months). In New York City, only 22.6% of the ATLL cases diagnosed were born in North America. Conclusions This is the largest epidemiological study of ATLL in the United States and shows a rising incidence in New York City. NHBs have a younger age at presentation and poor overall survival. The rising incidence is largely due to NHBs originating from the Caribbean.

Introduction In the United States, autologous hematopoietic cell transplantation (autoHCT) has fallen out of favor over chemotherapy consolidation for non–high-risk acute myeloid leukemia (AML) when allogeneic hematopoietic cell transplantation (alloHCT) is unfeasible, which is common in racial minorities because of donor registry under-representation and socioeconomic challenges. We compared autoHCT consolidation outcomes with chemotherapy alone in a minority-rich cohort in the Bronx. Patients and Methods We identified adults with favorable or intermediate cytogenetic risk AML in first complete remission after induction at Montefiore Medical Center from 1999 to 2015, and analyzed 81 patients who received consolidation with ≥2 cycles of chemotherapy, of whom 28 received autoHCT. Results The cohort predominantly consisted of ethnic/racial minorities (69%). Age, sex, race, presenting white cell count, and cytogenetic risk were similar between groups. The autoHCT group had longer relapse-free (RFS; 43 vs. 11 months; P = .003) and overall (OS) survival (not reached vs. 36 months; P = .043). Adjusted multivariable analysis showed significant benefit of autoHCT over chemotherapy alone for RFS (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.37-0.75; P Conclusion In this inner-city non–high-risk AML cohort, autoHCT provided OS and RFS benefit compared with chemotherapy alone. AutoHCT might constitute a valuable option for ethnic/racial minorities affected by significant barriers to alloHCT, whereas integration of measurable residual disease can help select patients more likely to benefit.

In the United States adult T cell lymphoma–leukemia (ATLL) carries a dismal prognosis and mainly affects immigrants from human T cell lymphotropic virus 1 endemic areas. Allogeneic hematopoietic stem cell transplant (alloHSCT) can be effective and is recommended as an upfront treatment in the National Comprehensive Cancer Network guidelines. We studied the barriers to alloHSCT in one of the largest ATLL populations in the United States. Comprehensive chart and donor registry reviews were conducted for 88 ATLL patients treated at Montefiore Medical Center from 2003 to 2018. Among 49 patients with acute and 32 with lymphomatous subtypes, 48 (59.5%) were ineligible for alloHSCT because of early mortality (52%), loss to follow-up (21%), uninsured status (15%), patient declination (10%), and frailty (2%). Among 28 HLA-typed eligible patients (34.6%), matched related donors were identified for 7 (25%). A matched unrelated donor (MUD) search yielded HLA-matched in 2 patients (9.5%), HLA mismatched in 6 (28.5%), and no options in 13 (62%). Haploidentical donors were identified for 6 patients (46%) with no unrelated options. There were no suitable donors for 7 (25%) alloHSCT-eligible patients. The main limitation for alloHSCT after donor identification was death from progressive disease (82%). AlloHSCT was performed in 10 patients (12.3%) and was associated with better relapse-free survival (26 versus 11 months, P = .04) and overall survival (47 versus 10 months, P = .03). Early mortality and progressive disease are the main barriers to alloHSCT, but poor follow-up, uninsured status, and lack of suitable donor, including haploidentical, are also substantial limitations that might disproportionally affect this vulnerable population. AlloHSCT can achieve long-term remissions, and strategies aiming to overcome these barriers are urgently needed to improve outcomes in ATLL.