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The effect of chronic graft-versus-host disease (cGVHD) on the risk of nonrelapse mortality (NRM) and relapse has not been specifically studied in older adults, who are increasingly undergoing allogeneic hematopoietic cell transplantation (alloHCT) and surviving long-term to develop cGVHD. In this Center for International Blood and Marrow Transplant Research (CIBMTR) analysis, we tested our hypothesis that the risk of NRM was higher with the development of cGVHD, particularly among older adults (age ≥60 years). We included 4429 adults age ≥40 years who underwent a first HLA-matched peripheral blood stem cell alloHCT for acute myelogenous leukemia or myelodysplastic syndrome between 2008 and 2017. We compared outcomes of 4 groups—older adults (≥60 years) and younger adults (40 to 59 years) with cGVHD and older and younger adults without cGVHD—to determine the effect of older age and cGVHD on various outcomes. We used Cox proportional hazard models to determine the risk of NRM, relapse, and overall survival (OS). We treated cGVHD as a time-dependent covariate. The severity of cGVHD was based on the CIBMTR clinical definitions. cGVHD was significantly associated with a higher risk of NRM and lower risk of relapse regardless of age. The risk of NRM was higher for older adults versus younger adults. Adults who developed cGVHD as a group had longer OS compared with age-matched cohorts without cGVHD. Older adults had worse OS regardless of cGVHD. Among adults with cGVHD, clinically moderate or severe cGVHD was associated with a significantly higher risk of NRM and lower risk of relapse; severe cGVHD was associated with shorter OS, whereas mild to moderate cGVHD was associated with longer OS. Among both younger and older adults, the development of cGVHD was associated with a higher risk of NRM, lower risk of relapse, and longer OS. Older adults had a higher risk of NRM, but the increased risk of NRM associated with cGVHD did not differ based on age. The development of mild to moderate cGVHD offered the most favorable balance between minimizing NRM and decreasing the risk of relapse. The relapse risk was lowest for adults with severe cGVHD, but high NRM resulted in shorter OS. Developing strategies to avoid clinically severe cGVHD is critically important. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

T-cell lymphoma (TCL) poses a therapeutic challenge. Allogeneic stem cell transplant (alloSCT) is frequently offered in primary refractory disease or failed autologous transplant. We systematically searched published articles on outcomes of alloSCT in TCL through PubMed and EMBASE database between January 2000 and October 2019. Among 651 identified studies, 22 (888 patients) were included. Forty percent patients had peripheral T-cell lymphoma not otherwise specified, 15% had angioimmunoblastic T-cell lymphoma, 21% had anaplastic large cell lymphoma, 5% had cutaneous T-cell lymphoma, and 19% had other histologic subtypes. Thirty-six percent patients had relapsed/refractory disease. Myeloablative conditioning regimens were used in 55% patients. At two-, three- and five-year post-transplant, overall survival was 57, 54 and 51%, respectively; progression-free survival was 45, 50 and 45%, respectively; non-relapse mortality was 9, 29 and 29%, respectively; relapse rate was 30, 28 and 29%, respectively. Our study shows that alloSCT provides durable remission in T cell lymphoma.

Limited information is available on the efficacy of post-transplantation cyclophosphamide (PTcy) or thymoglobulin for graft-versus-host disease (GVHD) prophylaxis in mismatched unrelated donor (MMUD) transplants. We retrospectively compared outcomes of 76 adult patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) who underwent 7/8 HLA-MMUD transplantation and received either PTcy (50 mg/kg on day 3 and 4) or thymoglobulin (total dose 4.5 mg/kg) for GVHD prophylaxis. In addition, tacrolimus and mycophenolate were used in both groups. Propensity score-based multivariable analyses (PSCA) were performed to adjust confounding effects of patient characteristics between both groups. Between January 2006 and June 2019, 25 patients received PTcy, and 51 received thymoglobulin. Median age of the population was 57 years, 78% of patients had AML, most common graft source was peripheral blood (96%), and 46% received myeloablative conditioning regimens. Median time to neutrophil (15 versus 11 days, P.001) and platelet engraftment (21 versus 15 days, P = .002) was prolonged in the PTcy group. The cumulative incidence of grade III-IV acute GVHD at day 100 was similar (12% versus 19.6%, P = .38), whereas chronic GVHD at 1 year was lower with PTcy compared to thymoglobulin (16% versus 49%, P = .006). Using PSCA, no difference in survival, relapse, relapse-free survival, and GVHD-free relapse-free survival was seen between groups. However, thymoglobulin was associated with higher incidence of acute (hazard ratio [HR] = 2.63, P = .01) and chronic GVHD (HR = 4.43, P = .03), and non-relapse mortality (HR 3.38, P = .04) compared to PTcy. Our study demonstrated that PTcy resulted in significantly lower rates of acute and chronic GVHD and non-relapse mortality compared to thymoglobulin in 7/8 HLA-MMUD transplants for AML and MDS.

Limited information is available on the impact of intensity of conditioning regimens in haploidentical peripheral blood stem cell transplant (haploPBSCT) with post-transplant cyclophosphamide (PTcy). We retrospectively compared outcomes of haplo-PBSCT between myeloablative (MAC) (n = 24) and reduced intensity conditioning (RIC) regimens (n = 65). Propensity score-based multivariable analyses were performed to adjust confounding effects of baseline characteristics between both groups. Eighty-nine patients underwent haplo-PBSCT between January 2012 and June 2019. For MAC and RIC, the cumulative incidences of grade III--IV acute GVHD were 4.2% and 3.1%, respectively (p = 0.92), and chronic GVHD were 18.9% and 36.5%, respectively (p = 0.08). Median follow-up for overall survival (OS) after MAC and RIC was 1.86 and 2.2 years, respectively. For MAC and RIC, one-year OS was 68.8% and 67.4%, respectively (p = 0.85); one-year relapse rate was 22.4% and 18.3%, respectively (p = 0.74); one-year relapse-free survival (RFS) was 56% and 59.7%, respectively (p = 0.87); and one-year non-relapse mortality (NRM) was 22% and 21.9%, respectively (p = 0.58). Using propensity score-based multivariable analyses, no difference in OS (HR 0.72, p = 0.51), relapse (SHR 0.63, p = 0.42), RFS (HR 0.74, p = 0.49) and NRM (SHR 1.11, p = 0.87) was noted between RIC and MAC. Our study shows no difference in outcomes between MAC and RIC regimens in haplo-PBSCT.

Anti-thymocyte globulin (ATG) targets in-vivo T lymphocytes. Variations in the recipient absolute lymphocyte count (ALC) might result in a variable exposure of ATG. We hypothesized that recipient ALC on the first day of ATG might predict transplant outcomes. We evaluated 217 patients undergoing 8/8 HLA-matched unrelated donor (MUD) peripheral blood stem cell transplant (PBSCT) between January 2005 and December 2017, and receiving rabbit ATG (Thymoglobulin, total dose 4.5 mg/kg) on days -3, -2 and -1. With a median follow up of 3.68 years for survival (OS), one-year OS, relapse rate, non-relapse mortality (NRM), and relapse-free survival (RFS) were 64.7%, 15.9%, 25.8%, and 58.4%, respectively. Multivariable analysis revealed that ALC100 k/mm

Maintenance therapy after first autologous transplant (autoSCT) improves progression-free survival (PFS) and overall survival (OS) in multiple myeloma (MM). However, efficacy of maintenance therapy after second autoSCT is unknown. We retrospectively evaluated outcomes of 111 adult MM patients who underwent second autoSCT between January 2000 and December 2018. Lenalidomide up to 15 mg daily or subcutaneous bortezomib 1.3 mg/m

Allogeneic stem cell transplant (alloSCT) is considered in diffuse large B cell lymphoma (DLBCL) patients with chemorefractory disease or who have relapsed after autologous SCT. Here we present the first report of alloSCT using the R-BEAM (rituximab, carmustine, etoposide, cytarabine, melphalan) conditioning regimen in DLBCL patients. We retrospectively compared long-term alloSCT outcomes of DLBCL patients who received either R-BEAM (n = 47) or reduced-intensity conditioning (RIC) regimens (n = 23). Seventy patients (median age, 53 years) with DLBCL received alloSCT between January 2005 and December 2017. The median number of pretransplant therapies was 3, and 17 patients (24%) received prior autologous SCT. All received rituximab as a frontline or salvage therapy before alloSCT. The donor was unrelated in 42 patients (60%), and peripheral blood stem cells were commonly used (96%). The 6-month cumulative incidence of grades III to IV acute graft-versus-host disease (GVHD) was 36.2% and 8.7% for R-BEAM and RIC, respectively (P = .03). Median follow-up of surviving patients after R-BEAM and RIC was 3.1 and 5.5 years, respectively. Three-year overall survival (OS) after R-BEAM and RIC was 34.4% and 43.4%, respectively (P = .48). At 3 years, R-BEAM was associated with a similar relapse rate (25.5% versus 26.1%, P = .96), nonrelapse mortality (NRM; 39.7% versus 39.1%, P = .98), and relapse-free survival (RFS; 34.8% versus 34.7%, P = .75) compared with RIC. In multivariable analysis lower Karnofsky performance score was associated with lower OS (hazard ratio, .96; P = .05), whereas chemorefractory disease was associated with a higher relapse risk (hazard ratio, 8.8; P = .04). No difference in OS, relapse, NRM, or RFS was noticed between R-BEAM and RIC. R-BEAM regimen seems to be feasible and results in equivalent rates of long-term OS, relapse, NRM, and RFS compared with RIC. However, a significantly higher rate of severe acute GVHD was noticed.

Hematopoietic cell transplantation from HLA-haploidentical related donors is increasingly used to treat hematologic cancers; however, characteristics of the optimal haploidentical donor have not been established. We studied the role of donor HLA mismatching in graft-versus-host disease (GVHD), disease recurrence, and survival after haploidentical donor transplantation with posttransplantation cyclophosphamide (PTCy) for 1434 acute leukemia or myelodysplastic syndrome patients reported to the Center for International Blood and Marrow Transplant Research. The impact of mismatching in the graft-versus-host vector for HLA-A, -B, -C, -DRB1, and -DQB1 alleles, the HLA-B leader, and HLA-DPB1 T-cell epitope (TCE) were studied using multivariable regression methods. Outcome was associated with HLA (mis)matches at individual loci rather than the total number of HLA mismatches. HLA-DRB1 mismatches were associated with lower risk of disease recurrence. HLA-DRB1 mismatching with HLA-DQB1 matching correlated with improved disease-free survival. HLA-B leader matching and HLA-DPB1 TCE-nonpermissive mismatching were each associated with improved overall survival. HLA-C matching lowered chronic GVHD risk, and the level of HLA-C expression correlated with transplant-related mortality. Matching status at the HLA-B leader and HLA-DRB1, -DQB1, and -DPB1 predicted disease-free survival, as did patient and donor cytomegalovirus serostatus, patient age, and comorbidity index. A web-based tool was developed to facilitate selection of the best haploidentical-related donor by calculating disease-free survival based on these characteristics. In conclusion, HLA factors influence the success of haploidentical transplantation with PTCy. HLA-DRB1 and -DPB1 mismatching and HLA-C, -B leader, and -DQB1 matching are favorable. Consideration of HLA factors may help to optimize the selection of haploidentical related donors.

There have been no large studies comparing reduced-intensity/non-myeloablative conditioning (RIC/NMA) to myeloablative conditioning (MAC) regimens in T-cell non-Hodgkin lymphoma (T-NHL) patients undergoing allogeneic transplant (allo-HCT). A total of 803 adults with peripheral T-cell lymphoma, anaplastic large cell lymphoma and angioimmunoblastic T-cell lymphoma (age 18-65 years), undergoing allo-HCT between 2008-2019 and reported to the Center for International Blood and Marrow Transplant Research with either MAC (n = 258) or RIC/NMA regimens (n = 545) were evaluated. There were no significant differences between the two cohorts in terms of patient sex, race and performance scores. Significantly more patients in the RIC/NMA cohort had peripheral blood grafts, haematopoietic cell transplantation-specific comorbidity index (HCT-CI) of ≥3 and chemosensitive disease compared to the MAC cohort. On multivariate analysis, overall survival (OS) was not significantly different in the RIC/NMA cohort compared to the MAC cohort (hazard ratio (HR) = 1.01, 95% confidence interval (CI) = 0.79-1.29; p = 0.95). Similarly, non-relapse mortality (NRM) (HR = 0.85, 95% CI = 0.61-1.19; p = 0.34), risk of progression/relapse (HR = 1.29; 95% CI = 0.98-1.70; p = 0.07) and therapy failure (HR = 1.14; 95% CI = 0.92-1.41, p = 0.23) were not significantly different between the two cohorts. Relative to MAC, RIC/NMA was associated with a significantly lower risk of grade 3-4 acute graft-versus-host disease (HR = 0.67; 95% CI = 0.46-0.99, p = 0.04). Among chemorefractory patients, there was no difference in OS, therapy failure, relapse, or NRM between RIC/NMA and MAC regimens. In conclusion, we found no association between conditioning intensity and outcomes after allo-HCT for T-cell NHL.

Chronic graft-versus-host disease (cGVHD) occurs in up to 25% of children following allogeneic hematopoietic cell transplantation (HCT) and continues to be a major cause of late morbidity and poor quality of life among long-term survivors of pediatric HCT. Late effects (LEs) of HCT are well documented in this population, and cGVHD has been identified as a risk factor for subsequent neoplasms (SNs) and several nonmalignant LEs (NM-LEs); however, the reported correlation between cGVHD and LEs varies among studies. We compared LEs occurring ≥2 years following childhood HCT for a hematologic malignancy in 2-year disease-free survivors with and without cGVHD and further evaluated the association of cGVHD features on the development of LEs. This systematic retrospective analysis used data from the Center of International Blood and Marrow Transplant Research (CIBMTR) on a large, representative cohort of 1260 survivors of pediatric HCT for hematologic malignancy to compare first malignant LEs and NM-LEs in those with a diagnosis of cGVHD and those who never developed cGVHD. The cumulative incidences of any first LE, SN, and NM-LE were estimated at 10 years after HCT, with death as a competing risk for patients with cGVHD versus no cGVHD. Cox proportional hazards models were used to evaluate the impact of cGVHD and its related characteristics on the development of first LEs. The estimated 10-year cumulative incidence of any LE in patients with and without cGVHD was 43% (95% CI, 38% to 48.2%) versus 32% (95% confidence interval [CI], 28.5% to 36.3%) (P.001), respectively. The development of cGVHD by 2 years post-HCT was independently associated with any LE (hazard ratio [HR], 1.38; 95% CI, 1.13 to 1.68; P = .001) and NM-LE (HR, 1.37; 95% CI, 1.10 to 1.70; P = .006), but not SN (HR, 1.30; 95% CI, .73 to 2.31; P = .38). cGVHD-related factors linked with the development of an NM-LE included having extensive grade cGVHD (HR, 1.60; 95% CI, 1.23 to 2.08; P = .0005), severe cGVHD (HR, 2.25; 95% CI, 1.60 to 3.17; P.0001), interrupted onset type (HR, 1.57; 95% CI, 1.21 to 2.05; P = .0008), and both mucocutaneous and visceral organ involvement (HR, 1.59; 95% CI, 1.24 to 2.03; P = .0002). No significant association between cGVHD-specific variables and SN was identified. Finally, the duration of cGVHD treatment of cGVHD with systemic immunosuppression was not significantly associated with SNs or NM-LEs. cGVHD was more closely associated with NM-LEs than with SNs among survivors of pediatric HCT for hematologic malignancy. In this analysis, the development of SNs was strongly associated with the use of myeloablative total body irradiation. cGVHD-related characteristics consistent with a state of greater immune dysregulation were more closely linked to NM-LEs.

Purpose. Women with locally advanced/high-risk triple-negative breast cancer treated with the current standard chemotherapy continue to have a poor prognosis. High-dose chemotherapy with autologous stem cell transplant as treatment for locally advanced/high-risk breast cancer remains controversial due to a lack of survival benefit seen in previous phase III trials. However, these trials evaluated a heterogeneous group of patients with different receptor subtypes. A marginal benefit was observed in certain subgroups. We report long-term outcomes of women with stage IIB or III triple-negative breast cancer treated with high-dose chemotherapy followed by autologous stem cell transplant at our institution between 1995 and 2001. Methods. This is a retrospective analysis of stage IIB or stage III triple-negative breast cancer treated with high-dose chemotherapy followed by autologous stem cell transplant. We excluded women with hormone-positive, HER2/neu-positive/unknown, and/or metastatic disease prior to transplant as per updated AJCC 7th edition guidelines. Patients underwent surgery and either neoadjuvant or adjuvant anthracycline and taxane-based chemotherapy and then proceeded to high-dose chemotherapy and autologous stem cell transplant using carmustine 600 mg/sqm, cyclophosphamide 5.6gm/sqm, and cisplatin 165 mg/sqm (STAMP 1 regimen) for consolidation. This was followed by locoregional breast and lymph node radiation per standard of care. Results. Twenty-nine women (2 stage IIB and 27 stage III) were evaluated. The median age at diagnosis was 43 years (IQR: 40, 51). Eleven patients had 4–9 regional lymph nodes (LN) involved and 16 had 10+ involved LNs. Four patients had T4 or inflammatory breast cancer and two had ipsilateral supraclavicular LNs involved. The median follow-up time is 16 years (95% CI: 12, 19, range

Key Points CIBMTR prognostic score predicts PFS and OS of patients with DLBCL receiving axicabtagene ciloleucel treatment after a prior autoHCT failure.CIBMTR high/very high-risk score marks an adverse risk cohort where novel immunotherapy or relapse prevention approaches are warranted., Visual Abstract, Allogeneic transplant (alloHCT) and chimeric antigen receptor modified (CAR)-T cell therapy are potentially cuarative options of diffuse large B-cell lymphoma (DLBCL) relapsing after an autologous (auto)HCT. Although the Center for International Blood and Marrow Transplant Research (CIBMTR) prognostic model can predict outcomes of alloHCT in DLBCL after autoHCT failure, corresponding models of CAR-T treatment in similar patient populations are not available. In this noncomparative registry analysis, we report outcomes of patients with DLBCL (≥18 years) undergoing a reduced intensity alloHCT or CAR-T therapy with axicabtagene ciloleucel during 2012 to 2019 after a prior auto-HCT failure and apply the CIBMTR prognostic model to CAR-T recipients. A total of 584 patients were included. The 1-year relapse, nonrelapse mortality, overall survival (OS), and progression-free survival for CAR-T treatment after autoHCT failure were 39.5%, 4.8%, 73.4%, and 55.7%, respectively. The corresponding rates in the alloHCT cohort were 26.2%, 20.0%, 65.6%, and 53.8%, respectively. The 1-year OS of alloHCT recipients classified as low-, intermediate- and high/very high-risk groups according to the CIBMTR prognostic score was 73.3%, 59.9%, and 46.3%, respectively (P = .002). The corresponding rates for low-, intermediate-, and high/very high-risk CAR-T patients were 88.4%, 76.4%, and 52.8%, respectively (P < .001). This registry analysis shows that both CAR-T and alloHCT can provide durable remissions in a subset of patients with DLBCL relapsing after a prior autoHCT. The simple CIBMTR prognostic score can be used to identify patients at high risk of treatment failure after either procedure. Evaluation of novel relapse mitigations strategies after cellular immunotherapies are warranted in these high-risk patients.

Simple Summary Immunotherapy has played a pivotal role in the management of relapsed DLBCL. Stem cell transplant and CAR T-cell therapy are curative treatment modalities for relapsed disease. Despite this, a subset of patients continues to progress, and their outcomes remain dismal. Newer therapeutic options to optimize outcomes as well as minimize toxicity are warranted. Abstract Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease. B-cell receptor (BCR) pathway is essential for malignant B-cell growth, survival, and proliferation. Various immune cells, including T-cells and macrophages in the tumor microenvironment (TME) contribute to tumor cell survival and pathogenesis of chemo-resistance. The presence of many targets on the malignant B-cells and in the TME has led to emergence of novel therapeutic agents. Stem cell transplant is the oldest treatment modality leveraging immune system in DLBCL. Subsequently, CD20 targeting monoclonal antibody and chimeric antigen receptor (CAR) T-cell therapy changed the treatment landscape of DLBCL. Recently, multiple novel immunotherapeutic agents have been added in the armamentarium for the management of DLBCL, and many are under development. In this review article, we will review latest updates of immunotherapeutic agents in the management of DLBCL.

International audience; Anti-PD-1 monoclonal antibodies yield high response rates in patients with relapsed/refractory classic Hodgkin lymphoma (cHL), but most patients will eventually progress. Allogeneic hematopoietic cell transplantation (alloHCT) after PD-1 blockade may be associated with increased toxicity, raising challenging questions about the role, timing, and optimal method of transplantation in this setting. To address these questions, we assembled a retrospective cohort of 209 cHL patients who underwent alloHCT after PD-1 blockade. With a median follow-up among survivors of 24 months, the 2-year cumulative incidences (CIs) of non-relapse mortality and relapse were 14 and 18%, respectively; the 2-year graft-versus-host disease (GVHD) and relapse-free survival (GRFS), progression-free survival (PFS), and overall survival were 47%, 69%, and 82%, respectively. The 180-day CI of grade 3-4 acute GVHD was 15%, while the 2-year CI of chronic GVHD was 34%. In multivariable analyses, a longer interval from PD-1 to alloHCT was associated with less frequent severe acute GVHD, while additional treatment between PD-1 and alloHCT was associated with a higher risk of relapse. Notably, post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis was associated with significant improvements in PFS and GRFS. While awaiting prospective clinical trials, PTCy-based GVHD prophylaxis may be considered the optimal transplantation strategy for this patient population.

While patients with double-hit lymphoma (DHL) are now frequently treated with intensive front-line immunochemotherapy, outcomes for those who fail these regimens and subsequently receive curative-intent second-line immunochemotherapy are unknown. We identified 55 such patients who achieved an overall/complete response rate of 29%/11%, median progression-free/overall survival (PFS/OS) of 2/5·1 months and one-year PFS/OS of 10/19% following the start of second-line therapy. These outcomes may serve as a standard against which future second-line treatment strategies for relapsed/refractory DHL can be measured and justify investigation of non-cytotoxic therapies in the second-line setting for these patients.

BACKGROUND Salvage immunochemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation is the standard-of-care second-line treatment for patients with relapsed/refractory diffuse large B-cell lymphoma after first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Outcomes after receipt of second-line immunochemotherapy in patients with aggressive B-cell lymphomas who relapse or are refractory to intensive first-line immunochemotherapy regimens (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab [R-EPOCH], rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and cytarabine [R-HyperCVAD], rituximab, cyclophosphamide, vincristine, doxorubicin, and high-dose methotrexate alternating with ifosfamide, etoposide, and cytarabine [R-CODOX-M/IVAC]) remain unknown. METHODS Outcomes of patients with non-Burkitt, aggressive B-cell lymphomas and relapsed/refractory disease after first-line treatment with intensive immunochemotherapy regimens who received platinum-based second-line immunochemotherapy were reviewed retrospectively. Analyses were performed to determine progression-free survival (PFS) and overall survival (OS) from the time of receipt of second-line immunochemotherapy. RESULTS In total, 195 patients from 19 academic centers were included in the study. The overall response rate to second-line immunochemotherapy was 44%, with a median PFS of 3 months and a median OS of 8 months. Patients with early treatment failure (primary refractory or relapse

Liver Graft-versus-host disease (GVHD) is common in patients with post-transplant liver dysfunction following allogeneic hematopoietic stem cell transplantation (AHSCT). Oftentimes, the diagnosis is made clinically, and liver biopsy is deferred. Our objective was to evaluate the risk factors and clinical outcomes of liver GVHD among patients who developed post-transplant liver dysfunction. Additionally, we evaluated the feasibility of liver biopsy in this population. We compared outcomes between liver GVHD and a “non-liver GVHD” group, which consisted of other etiologies of post-transplant liver dysfunction. Between January 2003 and December 2010, 249 patients developed post-transplant liver dysfunction following AHSCT: 124 patients developed liver GVHD and 125 were in the “non-liver GVHD” group. The incidence of acute and chronic liver GVHD at one year was 15.7% and 31.0%, respectively. The competing risk analysis revealed full intensity conditioning regimen (Hazard ratio [HR], 1.76; P = .008) and related donor (HR, 1.68; P = .004) as independent risk factors for liver GVHD. The time-varying covariate Cox regression analysis with competing risk event, demonstrated that liver GVHD was independently associated with higher non-relapse mortality, and adverse relapse-free and overall survival. A total of 112 liver biopsies were performed in 100 patients. No major complications were observed. Liver biopsy confirmed prebiopsy hypotheses in 49% of cases, and led to treatment modification in 49% of patients. Our study shows that liver GVHD is associated with adverse survival. Liver biopsy is safe and often helps directing care in this setting.

Post transplant cyclophosphamide (PTCy) graft-versus-host disease (GVHD) prophylaxis has allowed haploidentical (Haplo) transplantation to be performed with results similar to that after matched unrelated donor (MUD) transplantation with traditional prophylaxis. The relative value of transplantation with MUD versus Haplo donors when both groups receive PTCy/calcineurin inhibitor/mycophenolate containing GVHD prophylaxis is not known. We compared outcomes after 2036 Haplo and 284 MUD transplantations with PTCy GVHD prophylaxis for acute leukemia or myelodysplastic syndrome in adults between 2011 and 2018. Cox regression models were built to compare outcomes between donor types. Recipients of myeloablative and reduced intensity regimens were analyzed separately. Among recipients of reduced intensity regimens, 2-year graft failure (3% versus 11%), acute grade II-IV GVHD (HR 0.70, p=0.022), acute grade III-IV GVHD (HR 0.41, p=0.016) and non-relapse mortality (HR 0.43, p=0.0008) were lower after MUD compared to Haplo transplantation. Consequently, disease-free (HR 0.74, p=0.008; 55% versus 41%) and overall survival (HR 0.65, p=0.001; 67% versus 54%) were higher after MUD compared to Haplo transplants. Among recipients of myeloablative regimens, day-100 platelet recovery (95% versus 88%) was higher and grade III-IV acute (HR 0.39, p=0.07) and chronic GVHD (HR 0.66, p=0.05) were lower after MUD compared to Haplo transplantation. There were no differences in graft failure, relapse, non-relapse mortality, disease-free and overall survival between donor types with myeloablative conditioning regimens. These data extend and confirm the importance of donor-recipient HLA matching for allogeneic transplantation. A MUD is the preferred donor, especially for transplantations with reduced intensity conditioning regimens.

The information on the impact of cytokine release syndrome (CRS) on haploidentical donor peripheral blood stem cell transplant (haploPBSCT) outcomes is limited. We retrospectively evaluated 98 patients who underwent haploPBSCT between June 2012 and June 2019 for the onset and severity of CRS per the ASTCT guidelines. The incidence of CRS was 93% (91/98). Outcomes were compared between grade 1-2 and 3-4 CRS. Eighty-one patients developed grade 1-2 CRS (89%) and 10 (11%) developed grade 3-4 CRS. Compared to grade 1-2 CRS, grade 3-4 CRS experienced adverse survival (73.7% vs. 30%, p

Fludarabine 30 mg/m2/d × 5 and melphalan 140 mg/m2 × 1 (Flu-Mel140) is a commonly used reduced-intensity conditioning regimen. We hypothesized that addition of 200cGy total body irradiation (TBI) to Flu-Mel140 may improve antitumor activity and transplant outcomes. Primary objectives was overall survival (OS) at 3 years. Secondary objectives were to assess the cumulative incidences of acute and chronic GVHD, relapse-free survival (RFS), relapse rate, and nonrelapse mortality (NRM). We retrospectively evaluated outcomes of patients receiving Flu-Mel140-TBI followed by HLA-matched donor allogeneic hematopoietic stem cell transplantation (alloSCT) using peripheral blood stem cells. Eighty-one patients (median age, 58 years) underwent alloSCT between January 2008 and December 2018. Thirty-one percent of patients had a prior transplant, 32% had high or very-high disease risk index, and the donor was unrelated in 70% of patients. Grade 3 to 4 regimen-related toxicities were mucositis (37%), cardiac toxicity (17%), and renal toxicity (10%). The cumulative incidence of grade III to IV acute GVHD at day +100 was 24.7% and chronic GVHD at 1 year was 51.3%. Median follow-up for survival was 6.1 years. At 3 years, OS was 39.81%, RFS was 31.47%, and relapse rate was 30.5%. One-year NRM was 29.9%. Patients undergoing first transplantation experienced improved OS compared with second or beyond (63.08% versus 42.31%, P = .02). After adjusting for disease subtypes, age (≤55 versus 55), comorbidity index (CI), number of transplant and GVHD prophylaxis, multivariable analysis did not demonstrate any survival difference among disease subtypes. High CI (≥3) was predictive of adverse OS and NRM, whereas older age (>55 years) was associated with high NRM. Our study shows that Flu-Mel140-TBI seems feasible and provides durable disease control. Addition of TBI did not appear to improve outcomes compared to previously published reports of Flu-Mel140. Considerable NRM could result from the inclusion of patients with older age and prior transplants.

A head-to-head comparison of outcomes of unrelated donor allogeneic peripheral blood stem cell transplantation for AML between reduced intensity conditioning (RIC) and myeloablative conditioning (MAC) regimens using thymoglobulin for GVHD prophylaxis is limited. We evaluated outcomes of 122 AML patients who received either busulfan (Bu)/fludarabine (Flu)/low-dose total body irradiation (TBI) as RIC (n = 64, 52%) or Bu/Flu as MAC (n = 58, 48%), and thymoglobulin 4.5 mg/kg total dose between day - 3 to - 1 for GVHD prophylaxis. Grades III-IV acute GVHD (aGVHD) was lower with Bu/Flu/TBI compared with Bu/Flu (6.2% vs 26.1%, p = 0.009). At 1 year, Bu/Flu/TBI was associated with similar chronic GVHD (41.2% vs 44.8%, p = 0.75), OS (61.9% vs 56.9%, p = 0.69), relapse rate (29.9% vs 20.7%, p = 0.24), relapse-free survival (52.8% vs 50%, p = 0.80), non-relapse mortality (17.4% vs 29.3%, p = 0.41), and GVHD-free relapse-free survival (24.2% vs 27.5%, p = 0.80) compared with Bu/Flu. Multivariable analysis did not reveal any difference in outcomes between both regimens. In summary, thymoglobulin at 4.5 mg/kg did not have any adverse impact on survival when used with RIC regimen. Both Bu/Flu/TBI and Bu/Flu conditioning regimens yielded similar survival.

Introduction: CD19 directed CAR-T cell therapy has changed treatment paradigm of relapse refractory diffuse large B cell lymphoma (DLBCL). It is associated with certain unique toxicities including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), B-cell aplasia and hypogammaglobulinemia. However, the information on hematologic toxicity including neutropenia, thrombocytopenia and anemia is limited. Methods: We retrospectively evaluated patients who received CAR-T cell therapy for relapsed refractory DLBCL to estimate incidence, risk factors and outcomes of hematological toxicity especially pancytopenia. We also evaluated the impact of prophylactic G-CSF administration on incidence and duration of neutropenia, and infectious complications. Results: Between April 2018 and December 2020, 30 adult patients received CAR-T cell therapy (AxiCel=22, TisaCel=8). Median age of the population was 57 years (range, 23-81). Median time from diagnosis to CAR-T cell therapy was 674 days. Four patients each had double expressor and double hit subtypes. Seventy percent patients had extra-nodal disease, 60% of patients received three or more lines of therapy, 27% of patients received prior autologous stem cell transplant (autoSCT), and 23% patients received bridging therapy. All patients received Fludarabine and Cyclophosphamide (Flu/Cy) as a lymphodepleting therapy. CRS and ICANS were noted in 83% and 37% patients, respectively. One-year progression-free and overall survival were 49.76% and 85.91%, respectively. After CAR-T cell therapy, 93% (28/30) patients developed neutropenia with 17 (57%) experiencing absolute neutrophil count (ANC) Following CAR-T cell therapy, 86% (26/30) patients developed thrombocytopenia with two (7%) experiencing platelets Univariable analyses revealed that high dose of CAR-T cell was associated with decreased incidence of neutropenia (HR, 0.63; p=0.02), while absence of extra-nodal disease was associated with increased incidence of neutropenia (HR, 3.19; p=0.02). Moreover, patients with prior autoSCT had a lower likelihood of resolution of neutropenia (HR, 0.33; p=0.03), and those with multiple prior therapies had a lower likelihood of resolution of thrombocytopenia (HR, 0.36; p=0.002). Conclusion: Our study shows that a proportion of patients experienced prolonged hematological toxicity, and prior autoSCT and multiple lines of therapy were identified as risk factors. Prophylactic G-CSF did not appear to have any benefit on the prevention of neutropenia or infectious complications. Figure 1 Figure 1. Disclosures Deol: Kite, a Gilead Company: Consultancy. Modi: Genentech: Research Funding; Seagen: Membership on an entity's Board of Directors or advisory committees; MorphoSys: Membership on an entity's Board of Directors or advisory committees.

Background Chimeric Antigen Receptor (CAR) T cell therapy has emerged as a promising therapeutic option for relapsed/refractory non-Hodgkin lymphoma. However, access to CAR T cell therapy remains limited as CAR T cells are routinely administered in the hospital setting. Hence, there's a growing interest in standardizing outpatient administration of CAR T cells to increase patient access and minimize costs. Here, we describe our institution's experience with outpatient administration of CAR T cells. Methods In this retrospective study, we reviewed who received CAR T cell therapy in the outpatient setting at Karmanos Cancer Center between June 2019 and June 2021.Charts were reviewed for age, disease pathology, prior lines of therapy, need for hospitalization within 30 days, development of CRS and/or neurotoxicity, need for ICU admission, need for steroids and/or tocilizumab, length of admission, and disease state at last follow up. All patients received fludarabine and cyclophosphamide as lymphodepletion (LD) therapy day -5 to -3. CAR T cells were infused on day 0. Patients subsequently followed up in clinic daily for 2 weeks and were started on allopurinol, ciprofloxacin, fluconazole, acyclovir and levetiracetam. First response was assessed by FDG PET scan 4 weeks after CAR T cell . Results A total of 12 patients received CAR T cells during the study period. All patients had a diagnosis of DLBCL and received Tisagenlecleucel. Median age at CAR T cell therapy was 69.5 years (40-78 years). Median number of prior lines of therapy was (2-3) while 2 patients had received prior stem cell transplantation. Table 1 describes patient characteristics and lines of therapy. Two patients received bridging therapy prior to LD. Overall response rate was 58.3% (complete response-3, partial response-4). Median duration of follow up was 6.7 (0.6-13.8 months). Four patients required subsequent therapy after CAR T cell for disease progression while 9 patients were alive at the time of data cut off. Figure 1 summarizes disease response and follow . Table 2 summarizes complications during follow up. Nine (75%) patients developed anemia (grade 3-4 n=4, 33.3%), 8 (66.7%) developed thrombocytopenia (grade 3-4 n= 3, 37.5%), and 8 (66.7%) developed neutropenia (grade 3-4 n=8, 66.7%). Median time to platelet recovery to >,000 and neutrophil recovery to >500 was 66 days (44-81 days) and 11.5 days (6-65 days), respectively. Three (25%) patients required platelet and red blood cell transfusion support. Six (50%) patients developed cytokine release syndrome (CRS) with median grade 2 (range 1-3, grade 3-4 n=1). Five (5/6) patients required hospitalization, five (5/6) required tocilizumab, and one (1/6) required steroids. One (8.3%) patient developed neurotoxicity of grade 1 severity improved without systemic therapy. Six patients required hospitalization within 30 days of CAR T cell infusion. Median day of admission from CAR T cell infusion was 4 days (range 2-12 days (range 2-12 days, admission within 3 days n=2, admission under observation n=1). Patient characteristics at admission are summarized in table 3. Of these, 5 patients were diagnosed with CRS,1 patient with colitis and none with blood stream infection. Two patients required ICU admission. Median length of hospital admission was 5.5 days (2-9 days). All patients were alive at discharge while 1 patient required subsequent admission within 30 . Conclusion Outpatient administration of Tisagenlecleucel is feasible with low risk of hospital admission within 3 days of infusion. Adoption of outpatient CAR T cell therapy may increase patient access for treatment of DLBCL and diseases such as multiple myeloma while reducing administration costs for this novel therapy. Figure 1 Figure 1. Disclosures Modi: Genentech: Research Funding; Seagen: Membership on an entity's Board of Directors or advisory committees; MorphoSys: Membership on an entity's Board of Directors or advisory committees. Deol: Kite, a Gilead Company: Consultancy.

Introduction: Severe aplastic anemia (SAA) is a rare hematopoietic stem cell disorder characterized by hypocellular marrow and pancytopenia. Multiple factors play an important role in treatment approach include age, comorbidities, degree of pancytopenia and availability of stem cell donor to either immunosuppression irrespective (IST) or allogenic hematopoietic stem cell transplant (alloSCT). The use of nonmyeloablative conditioning regimen has improved the outcomes, however the choice for post-transplant GVHD prophylaxis remain a topic of debate. The use of mycophenolate mofetil (MMF) has been used as an alternative for methotrexate (MTX) as has shown to be associated with lower incidence of mucositis and shorter time to engraftment. Methods: We retrospectively evaluated consecutive adult patients with SAA who underwent alloSCT at Karmanoc Cancer Institute. All patients received fludarabine, cyclophosphamide and antithymocyte globulin for conditioning regimen with calcineurin inhibitors (CNI) and MMF for GVHD prophylaxis. MMF was started at day -3 at 15 mg/kg three times daily and stopped at day +30 in the absence of active GVHD. The primary objectives were to estimate cumulative incidence of acute (aGVHD) and chronic GVHD (cGVHD) and overall survival (OS). Secondary objectives were to evaluate time to engraftment, days of hospitalization and incidence of mucositis. Results: From January 2005 and May 2019, 33 patients with SAA underwent alloSCT. Patient characteristics are detailed in Table 1. Median age was 36 years (range, 18-71). Twenty-seven patients received bone marrow stem cells (82%) and six patients received peripheral blood stem cells (18%). Thirty patients (91%) received 8/8 HLA matched donor and three patients (9%) received 7/8 HLA matched donor. Sixteen patients (48%) received stem cells from sibling donor and 17 patients (52%) received stem cells from unrelated donor. Thirteen patients (39%) had received IST prior to alloSCT, and 20 patients (61%) received upfront alloSCT. For GVHD prophylaxis all patients received MMF and CNI (tacrolimus=32, and cyclosporine=1). Median time from diagnosis to transplant was 15.8 months for patients who received IST prior to alloSCT and 2 months for patients who received upfront alloSCT. Median time to platelet engraftment was 13.5 days and neutrophil engraftment was 12 days, while one patient experienced graft failure. The median number of days for hospital stay were 25 days. Four patients (11%) developed grade I-II mucositis, no grade III-IV mucositis was observed in the first 30 days and 6 patients had CMV reactivation. The 100-day cumulative incidence rate of grade II-IV aGVHD was 21.2% (95% CI, 9.2 - 36.5), grade III-IV aGVHD was 9.1% (2.3-21.9) and 1-year CIR of cGVHD was 21.2% (95% CI, 9.2-36.5). Comparing patients who received IST prior to alloSCT versus upfront alloSCT, the 100-day CIR of grade II-IV aGVHD was 30.8% (95% CI, 8.2 - 56.5) and 15% (95% CI, 3.6 - 34.0), respectively, (Gray p=0.26) and the 3-year CIR of cGVHD was 39.6% (95% CI, 13.1 - 65.5) and 27.8% (95% CI, 9.2 - 50.3), respectively, (Gray p=0.37). Comparing patients who received alloSCT from related versus unrelated donor, 100-day CIR of II-IV aGVHD was 12.5% (95% CI, 1.9 - 33.6) and 29.4% (95% CI, 10.2 - 51.9), respectively, (Gray p=0.26), and the 3-year CIR of cGVHD was 34.2% (95% CI, 11.4 - 58.9) and 29.4% (95% CI, 10.1 - 52.0), respectively (Gray p=0.90). Median follow up of surviving patient was 5 years (95% CI, 3.1-6.8). Three-year OS was 87% (95% CI, 75.7- 99.9) and median OS was not reached. Six patients died by the time of the analysis, one patient died from graft failure (86 days after transplant from 8/8 HLA MUD), two patients died due infectious complications (808 days and 1637 days after transplant), three patients died due to multiorgan failure (215, 297 and 1097 days after transplant). Conclusion: Our data with use of CNI and MMF for GVHD prophylaxis for SAA following alloSCT with nonmyeloablative conditioning regimen showed that the rate of mucositis was low, engraftment time was rapid, and hospitalization was short, while OS, rates of acute and chronic GVDH were comparable to previously published rates with CNI and MTX-based GVHD prophylaxis. Figure 1 Figure 1. Disclosures Modi: Genentech: Research Funding; Seagen: Membership on an entity's Board of Directors or advisory committees; MorphoSys: Membership on an entity's Board of Directors or advisory committees. Deol: Kite, a Gilead Company: Consultancy.

Background: Double hit lymphoma (DHL) accounts for approximately 10-14% of diffuse large B cell lymphoma (DLBCL) and is characterized by the presence of rearrangements affecting MYC and either BCL2 and/or BCL6 by FISH. The complete response (CR) rate with standard R-CHOP is very poor at 20%, with dismal long-term progression-free (PFS) and overall survival (OS). Aggressive chemotherapy regimens including R-EPOCH, R-HyperCVAD/MA, and R-CODOX-M/IVAC have been evaluated in retrospective studies and have demonstrated better PFS compared to R-CHOP. However, no OS benefit is noted. Moreover, these regimens are associated with significant toxicity and cannot be used in a substantial proportion of patients due to advanced age and comorbidities, and have not been evaluated in prospectively studies. Therefore, new therapeutic modalities, which are better tolerated, are indeed needed to improve outcomes in this high-risk population. Polatuzumab vedotin (PoV) is a CD79b-directed antibody-drug conjugate delivering monomethyl auristatin E (MMAE). PoV either as a single agent or with bendamustine and rituximab (BR) demonstrated encouraging activity in relapsed refractory DLBCL with an overall response rate (ORR) of approximately 50%. Given the promising activity, PoV has been combined with rituximab, cyclophosphamide, doxorubicin, prednisone (R-CHP) in a phase 1b/2 trial, and has shown a favorable safety and tolerability profile. Study design and Methods: This is a phase II, multicenter, open label study of PoV 1.8 mg/kg in combination with standard doses of R-CHP in patients with untreated double or triple hit lymphoma. One cycle of R-CHOP prior to enrollment is allowed. Key eligibility criteria include patients aged > 18 years with previously untreated double or triple hit lymphoma, ECOG PS 0 to 2, measurable FDG-avid disease. Key exclusion criteria are DLBCL NOS subtype, primary mediastinal or Burkitt's lymphoma, and CNS involvement. A total of 49 patients will be enrolled. All patients will receive PoV with R-CHP every 3 weeks for a total of 6 cycles with intrathecal methotrexate for CNS prophylaxis. The primary endpoint is CR rate. Key secondary endpoints are PFS, OS, ORR, duration of response, and safety and tolerability of the combination. Disease response will be assessed by the Lugano response criteria. The study is currently enrolling. ClinicalTrials.gov Identifier: NCT04479267. Disclosures Modi: Genentech: Research Funding; Seagen: Membership on an entity's Board of Directors or advisory committees; MorphoSys: Membership on an entity's Board of Directors or advisory committees. Pregja: Janssen: Consultancy; Regeneron: Consultancy; Takeda: Consultancy; Amgen: Consultancy; Intellia: Consultancy; Caelum: Consultancy; Alnylam: Consultancy; Eidos: Consultancy; BMS: Research Funding. Ramchandren: pharmacyclics: Consultancy, Research Funding; Trillium: Research Funding; curis: Research Funding; BMS: Consultancy; MERCK: Consultancy, Research Funding; seattle genetics: Consultancy, Research Funding.

Patients who relapse after allogeneic HCT have a poor prognosis and few effective treatment options. Responses to salvage therapy with donor lymphocyte infusions (DLI) are driven by a graft versus leukemia (GvL) effect. However, relapses and moderate to severe graft versus host disease (GVHD) are common. Therapies that increase the GvL effect without inducing GVHD are needed. The NEXI-001 study is a prospective, multicenter, open-label phase 1/2 trial designed to characterize the safety, immunogenic, and antitumor activity of the NEXI-001 antigen specific T-cell product. This product is a donor-derived non-genetically engineered therapy that consists of populations of CD8+ T cells that recognize HLA 02.01-restricted peptides from the WT1, PRAME, and Cyclin A1 antigens. These T cells consist of populations with key memory phenotypes, including stem-like memory, central memory, and effector memory cells, with a low proportion ( In conclusion, these results show that infusion of the NEXI-001 product is safe and capable of generating a cell-mediated immune response with early signs of clinical activity. A second infusion is associated with increasing the level of antigen specific CD8+ T cells and their persistence in PB and BM. TCR sequencing and RNA Seq transcriptional profiling of the CD8+ T cells are planned, and these data will be available for presentation during the ASH conference. At least two cycles of 200M NEXI-001 cells weekly x 3 weeks of a 4-week cycle is planned for the next dose-escalation cohort. Early data suggest that the NEXI-001 product has the potential to enhance a GvL effect with minimal GVHD-associated toxicities. Disclosures Al Malki: Jazz Pharmaceuticals, Inc.: Consultancy; Neximmune: Consultancy; Hansa Biopharma: Consultancy; CareDx: Consultancy; Rigel Pharma: Consultancy. Vasu: Boehringer Ingelheim: Other: Travel support; Seattle Genetics: Other: travel support; Kiadis, Inc.: Research Funding; Omeros, Inc.: Membership on an entity's Board of Directors or advisory committees. Modi: MorphoSys: Membership on an entity's Board of Directors or advisory committees; Seagen: Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding. Perales: Sellas Life Sciences: Honoraria; Novartis: Honoraria, Other; Omeros: Honoraria; Merck: Honoraria; Takeda: Honoraria; Karyopharm: Honoraria; Incyte: Honoraria, Other; Equilium: Honoraria; MorphoSys: Honoraria; Kite/Gilead: Honoraria, Other; Bristol-Myers Squibb: Honoraria; Celgene: Honoraria; Medigene: Honoraria; NexImmune: Honoraria; Cidara: Honoraria; Nektar Therapeutics: Honoraria, Other; Servier: Honoraria; Miltenyi Biotec: Honoraria, Other. Edavana: Neximmune, Inc: Current Employment. Lu: Neximmune, Inc: Current Employment. Kim: Neximmune, Inc: Current Employment. Suarez: Neximmune, Inc: Current Employment. Oelke: Neximmune, Inc: Current Employment. Bednarik: Neximmune, Inc: Current Employment. Knight: Neximmune, Inc: Current Employment. Varela: Kite: Speakers Bureau; Nexlmmune: Current equity holder in publicly-traded company, Honoraria, Membership on an entity's Board of Directors or advisory committees.

Relapse after allo-HSCT is the leading cause of death in patients with AML. While donor lymphocyte infusions (DLI) achieve modest graft-versus-leukemia (GVL) effects in a small group of responders, responses are often accompanied by significant morbidity and mortality from graft-versus host disease (GVHD). Therefore, there is a significant need for cellular approaches that enhance the benefit of GVL while decoupling toxicities associated with GVHD. Herein, we report initial results from a first-in-human study of a non-genetically engineered adoptive cellular therapy product, NEXI-001, which contains populations of anti-leukemia antigen-specific CD8+ T cells. NEXI-001is generated using a novel technology platform referred to as Artificial Immune Modulation (AIM). Specifically, nano-artificial Antigen Presenting Cells are used in combination with a proprietary cellular expansion system to isolate and expand populations of CD8+ T cells that recognize five specific HLA 02.01-restricted peptides from the WT1, PRAME, and Cyclin A1 antigens, each of which is commonly over-expressed on AML blasts and leukemic stem cells. The ability to direct T cells against multiple leukemic antigens may reduce potential for tumor escape via target down-regulation. The AIM manufacturing process is optimized to consistently produce cellular products that contain T cell subtypes which combine anti-tumor potency with long-term persistence. Each NEXI-001 product is comprised of >95% memory T cells, and include stem-like central memory (Tscm), central memory (Tcm) and effector memory (Tem) cells - those T cell subtypes with potential to provide long lasting GVL effects. Importantly, each product also contains very low proportions of naïve T cells with allo-reactive potential (Tn), which may further reduce the risk of GVHD. (Table 1) Patients underwent bridging therapy to control leukemic burden while NEXI-001 T cells were manufactured for 14 days. After a 14-day wash out period, lymphodepleting therapy (fludarabine 30mg/m2, Cytoxan 300mg/m2 D-5 to D-3) was given followed by two rest days before NEXI-001 cell infusion. Dose levels for Phase 1 patients enrolled include safety D-1 (50 million T cells, n=1); followed by two additional dose-escalating safety cohorts {100 million T cells (n=3); and 200 million T cells, (n=3)}, and expansion cohort (n=16). A total of 7 AML patients (median age 43) with HLA-02:01 who had relapsed after allo-HSCT have been enrolled to-date. The same HLA-matched donor PBMCs are used for NEXI-001 manufacturing. Median time from previous SCT to relapse was 10 months, median bone marrow blast at relapse was 9%. and all patients were determined as poor risk category. To-date, there have been no infusion reactions, CRS or ICANS events observed for any patient treated. Significantly, there is no evidence of GVHD in any patient (n=3). Analysis of primary end point demonstrates a safe and well tolerated profile. Analyses of secondary end points support early signs of clinical response. We observed early and significant in vivo T cell proliferation as early as Day 5 (Figure 1). This may suggest that NEXI- T cells are actively engaging leukemic targets. Multimer staining confirmed the presence of NEXI-001 T cells in peripheral blood (Figure 2). Uniquely, the CD8+ T cells in peripheral blood maintain the phenotype subsets of the infused product over all time points measured (Figure 3). Despite complete lymphodepletion, CD4 reconstitution is robust, earlier than expected and consistent with increased levels of IL2. Evidence of cytotoxic activity, likely mediated by CD8+ T cells, was evident with increased serum levels of IFNg, TNFa, Granzymes A and B, and sFas. Additionally, we observed recruitment and trafficking of CD4 T cells to the bone marrow which may contribute to the initiation of a more robust cell-mediated immune response. Maintaining populations of T-stem cell and T-central memory subtypes may provide marrow-resident effector T cells with a source of continued replenishment over time, providing potential for a durable anti-tumor response. In conclusion, early results suggest that infusion of NEXI-001 product, is safe, well tolerated and capable of generating an early and robust cell-mediated immune response in patients with relapsed AML post allo-HSCT. As a novel cellular therapy, NEXI-001 may have potential to enhance the benefit of GVL while decoupling the toxicities associated with GVHD. Disclosures Al Malki: Neximmune: Consultancy; Jazz Pharmacuticals, Inc: Consultancy; Rigel Pharma: Consultancy. Perales:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Honoraria, Research Funding; Miltenyi Biotec: Research Funding; Medigene: Membership on an entity's Board of Directors or advisory committees, Other; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Nektar Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Honoraria; Servier: Membership on an entity's Board of Directors or advisory committees, Other; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria; Incyte Corporation: Honoraria, Research Funding; MolMed: Membership on an entity's Board of Directors or advisory committees; Omeros: Honoraria, Membership on an entity's Board of Directors or advisory committees; NexImmune: Membership on an entity's Board of Directors or advisory committees; Cidara Therapeutics: Other; Bellicum: Honoraria, Membership on an entity's Board of Directors or advisory committees. Modi:MorphoSys: Membership on an entity's Board of Directors or advisory committees. Vasu:Janssen: Membership on an entity's Board of Directors or advisory committees; Kiadis Inc: Other: Kiadis has obtained exclusive licensing requirements from The OHio State University; Omeros: Membership on an entity's Board of Directors or advisory committees. Kim:Neximmune: Current Employment. Wang:Neximmune: Current Employment. Lu:Neximmune: Current Employment. Oelke:Neximmune: Current Employment. Myint:Neximmune: Current Employment, Current equity holder in private company; BMS: Current equity holder in publicly-traded company; Celgene: Ended employment in the past 24 months. Varela:Neximmune: Consultancy, Current equity holder in private company.

PURPOSE: Although fluoroquinolone prophylaxis is frequently utilized in autologous hematopoietic stem cell transplant (AHSCT) patients, its impact on morbidity and mortality is uncertain. This study investigates the role of quinolone prophylaxis after AHSCT in recent years. METHODS: We conducted a retrospective review of 291 consecutive adult patients who underwent AHSCT for malignant disorders, between June 2013 and January 2015. Outcomes were compared between patients who received norfloxacin prophylaxis and those who did not. The endpoints were mortality during prophylaxis and at 100 days after transplant, frequency of ICU admissions, and incidence and type of bacteremia. RESULTS: Of 291 patients, 252 patients received norfloxacin prophylaxis and 39 patients did not. The mortality during prophylaxis and at 100 days as well as the median number of days of hospitalization following AHSCT did not differ between the two groups. No differences were noted in the frequency of ICU admission, incidence of septic shock, and duration of ICU stay. Patients who did not receive prophylaxis had a significantly higher rate of neutropenic fever (97%) than patients who received prophylaxis (77%) (p = 0.005). The patients with prophylaxis demonstrated a significantly higher rate of gram-positive bacteremia as compared to those without prophylaxis (p = 0.002). Frequency of Clostridium difficile infection was similar during and post-prophylaxis. More antibiotic use was noted among patients without prophylaxis [97%; median 9 (range, 5–24) days] compared to patients with prophylaxis [79%; median 7 (range, 3–36) days, p = 0.04]. CONCLUSION: Although fluoroquinolone prophylaxis reduced the incidence of neutropenic fever and antibiotic use in AHSCT, it did not alter mortality or morbidity.

Introduction: Haploidentical donor transplant (HIDT) with high dose post-transplant cyclophosphamide (PTcy) has shown promising results in terms of GVHD and survival. PTcy when given on day +3 and +4 is associated with considerable morbidity. In our previous analysis, we demonstrated that when compared to matched donor allogeneic stem cell transplant, HIDT with PTcy was associated with significantly higher rates of hypoxia, grade 3-4 mucositis and hemorrhagic cystitis (Modi et al, JCO 2020). PTcy is known to cause cardiomyopathy. However, a comprehensive analysis of cardiac toxicity occurring from PTcy is limited. Methods: We retrospectively evaluated adult patients (pt) who underwent HIDT with PTcy to evaluate incidence and risk factors of cardiac toxicities. Source of stem cell was peripheral blood in all patients, and all received PTcy-based GVHD prophylaxis. We aimed to evaluate impact of cardiac toxicity on NRM and OS. We compared outcomes between two groups: cardiac toxicity and no-cardiac toxicity. Results: Between June 2012 and June 2019, 98 pt underwent HIDT. Of these, 21 (21.4%) developed cardiac toxicity and 77 (78.6%) did not. Median day to onset of cardiac toxicity from HIDT was 7 days, and median duration of cardiac toxicity was 14 days. Fourteen pt (67%) had resolution of the cardiac toxicity. Median age of the patient was significantly higher in the cardiac toxicity than no-cardiac toxicity (65 vs 57 years, p=0.007). Following cardiac toxicities were observed: systolic heart failure (n=7, 34%), diastolic heart failure (n=2, 10%), atrial fibrillation (n=10, 48%), pericardial effusion (n=2, 9%) one of which required pericardial window, pericarditis (n=1, 5%) and supraventricular tachycardia (n=1, 5%). In patients with congestive heart failure, the median LVEF was 45% (range, 20-60). Majority of the cardiac toxicities were de-novo in origin, while sepsis-induced cardiac toxicity was present in one pt. The proportion of male patients was higher in the cardiac toxicity than no-cardiac toxicity (81% vs 55%, p=0.04). Median KPS was marginally lower (70% vs 80%, p=0.08) and median donor age was marginally higher (59 vs 51 years, p=0.08) in the cardiac toxicity group compared to no-cardiac toxicity. Median Co-morbidity index was 1 for both groups. Patients in the cardiac toxicity had higher rate of pre-transplant coronary artery disease compare to no-cardiac toxicity group (24% vs 6%, p=0.03). No difference in the pre-transplant cardiac function was noted between both groups (LVEF 55% vs 60%, p=0.76). Six pt (29%) in the cardiac toxicity and 30 pt (39%) in the no-cardiac toxicity received myeloablative conditioning regimen (p=0.45). Grade 3-4 cytokine release syndrome was higher in the cardiac toxicity compared to the other group (20% vs 6%, p=0.04). Median follow-up of surviving patients was 1.9 years in both groups. For cardiac toxicity and no-cardiac toxicity, 1-year OS was 38.1% and 76.4% (HR 0.25, 95% CI 0.13-0.48, p≤0.001), respectively; and 1-year NRM was 57.1% and 13.1%, respectively (P≤0.001). Multivariable analysis was performed to evaluate risk factors associated with cardiac toxicity, and older age (OR 1.05, 95% CI 1.00-1.10, p=0.08) and male sex (OR 0.34, 95% CI 0.08-1.13, p=0.096) were marginally associated with higher risk of cardiac toxicity. No impact of intensity of conditioning regimen was noted. Multivariable analysis revealed adverse OS (HR 0.20, 95% CI 0.09-0.43, p Conclusion: Cardiac toxicity was associated with worse OS and higher NRM. Older age and male sex may have higher risk of developing cardiac toxicity. Early supportive care and aggressive cardiac management may help improve outcomes. Figure Disclosures Deol: Kite, a Gilead Company: Consultancy; Novartis: Consultancy. Modi:MorphoSys: Membership on an entity's Board of Directors or advisory committees.

Introduction: Post-transplant cyclophosphamide (PT-Cy) in HLA-haploidentical hematopoietic cell transplantation (Haplo-HCT) results in acceptable engraftment and graft-versus-host disease (GVHD). Results of BMT CTN 1203 that compared matched unrelated donor (MUD) HCT with PT-Cy containing to calcineurin inhibitor (CNI) containing GVHD prophylaxis following reduced intensity conditioning, showed better 1-year GVHD free relapse free survival with PT-Cy. The relative value of a MUD versus a Haplo donor in the context of PT-Cy is not known. In this study we compared outcomes after Haplo- and MUD HCT with PT-Cy containing GVHD prophylaxis. Methods: Eligible patients were aged >18 years and received haplo-HCT or MUD HCT for AML, ALL and MDS in the US from 2011-2018. Patients received myeloablative (n=1001) or reduced intensity (n=1398) regimens and were analyzed separately. All recipients of haplo-HCT and reduced intensity conditioning MUD HCT received PT-Cy + CNI + mycophenolate mofetil (MMF) for GVHD prophylaxis. Among recipients of myeloablative conditioning MUD HCT, 55% received PT-Cy + CNI + MMF and 45%, PT-Cy + CNI. Cox regression models were built to compare outcomes between donor types. As PT-Cy containing GVHD prophylaxis for myeloablative conditioning MUD HCT is recent; therefore, outcomes were censored at 1-year. A p-value ≤0.01 was considered significant. Results: Myeloablative conditioning regimen: Age at transplant, sex, performance score, co-morbidity and CMV serostatus did not differ between recipients of haplo- and MUD HCT. Haplo-HCT recipients were less likely to be Caucasian (69% vs. 91%). They were also more likely to have AML (55% vs. 47) and less likely to have MDS (13% vs. 31%). Disease risk index did not differ between treatment groups. The predominant conditioning regimen for haplo-HCT was total body irradiation (TBI) + fludarabine (44%) for Haplo-HCT and for MUD HCT, fludarabine + busulfan ± thiotepa (59%). Engraftment rates did not differ between groups. Results of multivariate analyses are shown in Table 1. Compared to Haplo-HCT, grade II-IV acute GVHD risk was higher after MUD-HCT with PT-Cy + CNI GVHD prophylaxis. There were no differences in grade III-IV acute or chronic GVHD risk between treatment groups. Non-relapse mortality, relapse, disease-free and overall survival did not differ between treatment groups. Reduced intensity conditioning regimen: Age at transplant, sex, performance score, co-morbidity and CMV serostatus did not differ between recipients of haplo- and MUD HCT. Haplo-HCT recipients were less likely to be Caucasian (72% vs. 95%). Haplo-HCT recipients were less likely to have MDS (19% vs. 24%). Disease risk index did not differ between treatment groups. The predominant conditioning regimen was TBI 200 cGy + fludarabine + cyclophosphamide (88%) for Haplo-HCT and for MUD HCT, TBI 200 cGy + fludarabine + cyclophosphamide (37%) and fludarabine + melphalan (33%). Engraftment rates did not differ between groups. Results of multivariate analyses are shown in Table 2. Compared to Haplo-HCT acute and chronic GVHD risks did not differ between treatment groups. However, non-relapse mortality was lower after MUD-HCT which led to higher disease-free and overall survival. Conclusion: In patients who received myeloablative conditioning and PT-Cy + CNI + MMF GVHD prophylaxis, haploidentical related and matched unrelated donors are comparable. However, in patients who received less intense conditioning regimens, disease free and overall survival was higher after MUD HCT compared to Haplo-HCT. Disclosures Arora: Fate Therapeutics: Consultancy; Pharmacyclics: Research Funding; Kadmon: Research Funding; Syndax: Research Funding. Al Malki:Neximmune: Consultancy; Jazz Pharmacuticals, Inc: Consultancy; Rigel Pharma: Consultancy. Brunstein:Magenta: Research Funding; Gamida: Research Funding; Astex: Research Funding; AlloVir: Other: Advisory board. Grunwald:Merck: Consultancy; Agios: Consultancy; Abbvie: Consultancy; Agios: Consultancy; Celgene: Consultancy; Incyte: Consultancy, Research Funding; Premier: Consultancy; Amgen: Consultancy; Amgen: Consultancy; Merck: Consultancy; Cardinal Health: Consultancy; Celgene: Consultancy; Abbvie: Consultancy; Cardinal Health: Consultancy; Merck: Consultancy; Cardinal Health: Consultancy; Daiichi Sankyo: Consultancy; Agios: Consultancy; Abbvie: Consultancy; Incyte: Consultancy, Research Funding; Pfizer: Consultancy; Daiichi Sankyo: Consultancy; Astellas: Consultancy; Daiichi Sankyo: Consultancy; Premier: Consultancy; Trovagene: Consultancy; Astellas: Consultancy; Astellas: Consultancy; Premier: Consultancy; Trovagene: Consultancy; Trovagene: Consultancy; Genentech/Roche: Research Funding; Janssen: Research Funding; Genentech/Roche: Research Funding; Genentech/Roche: Research Funding; Forma Therapeutics: Research Funding; Merck: Research Funding; Janssen: Research Funding; Forma Therapeutics: Research Funding; Forma Therapeutics: Research Funding; Incyte: Consultancy, Research Funding; Pfizer: Consultancy; Celgene: Consultancy; Amgen: Consultancy; Pfizer: Consultancy. Kekre:Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Gilead: Consultancy, Honoraria. McGuirk:Juno Therapeutics: Consultancy, Honoraria, Research Funding; Allo Vir: Consultancy, Honoraria, Research Funding; Astellas: Research Funding; Fresenius Biotech: Research Funding; Novartis: Research Funding; Kite Pharmaceuticals: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pluristem Ltd: Research Funding; Gamida Cell: Research Funding; Bellicum Pharmaceutical: Research Funding. Mehta:CSL Behring: Research Funding; Incyte: Research Funding; Kadmon: Research Funding. Modi:MorphoSys: Membership on an entity's Board of Directors or advisory committees. Reshef:Gilead: Consultancy, Honoraria, Other: Travel support, Research Funding; Immatics: Research Funding; Celgene: Consultancy; Takeda: Research Funding; Monsanto: Consultancy; Incyte: Research Funding; Shire: Research Funding; Novartis: Honoraria; Pharmacyclics: Research Funding; Magenta: Consultancy; Bristol-Myers Squibb: Research Funding; Kiadis: Research Funding; Bluebird: Research Funding; Atara: Consultancy, Research Funding. Schroeder:Partners Therapeutics: Other; Gilead Sciences Inc: Other; Pfizer: Other; Genentech Inc: Research Funding; Incyte Corporation: Other: served on advisory boards and received honoraria or consultant fees, Research Funding; Novo Nordisk: Other; Merck: Consultancy, Honoraria, Speakers Bureau; AbbVie: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Speakers Bureau; GSK: Other; FlatIron Inc: Other; Dova Pharmaceuticals: Other; Astellas: Other; Janssen: Research Funding; Genzyme Sanofi: Other: served on advisory boards and received honoraria or consultant fees, Research Funding; PBD Incorporated: Research Funding; Celgene: Research Funding; Amgen: Other: served on advisory boards and received honoraria or consultant fees, Research Funding; Seattle Genetics: Research Funding; Fortis: Research Funding; Cellect Inc: Research Funding. Soiffer:alexion: Consultancy; Rheos Therapeutics: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy; VOR Biopharma: Consultancy; Gilead: Consultancy; Be the Match/ National Marrow Donor Program: Membership on an entity's Board of Directors or advisory committees; Kiadis: Membership on an entity's Board of Directors or advisory committees; Precision Bioscience: Consultancy; Mana Therapeutics: Consultancy; Cugene: Consultancy; Juno: Membership on an entity's Board of Directors or advisory committees. Waller:Verastem Oncology, Inc: Consultancy, Research Funding.

Introduction: Mantle cell lymphoma (MCL) is a rare subtype of Non-Hodgkin lymphoma (NHL) accounting for approximately 6% of all NHL. Currently, there is no standard first line induction therapy and initial therapy is based on patient age, performance status and physician preference. Limited information is available comparing outcomes of patients who achieve first complete remission (CR1) with low intensity regimens versus high intensity regimens followed by autologous stem cell transplant (ASCT). Methods: We conducted a retrospective chart review of adult MCL patients who underwent ASCT in CR1. Patients were divided into 2 groups based on the induction regimens: low intensity regimens ((R-CHOP, BR) versus high intensity regimens (Hyper-CVAD, Nordic Regimen, R-CHOP alternating with R-DHAP, R-DHAP). The primary objective was to compare relapse-free survival (RFS), overall survival (OS) and NRM (non-relapse mortality) between both groups. Results: Between January 2005 and December 2016, 66 patients with CR1 received R-BEAM conditioning regimen followed by ASCT. Twenty-five patients (38%) received low intensity regimens: R-CHOP (n=21, 84%) and BR (n=4; 16%). Forty one patients (62%) received high intensity regimens: Hyper-CVAD (n=28, 68%), Nordic regimen (n=9, 22%), R-CHOP alternating with R-DHAP (n=1, 2%) and Hyper-CVAD that was changed due to intolerability (1 changed to R-CHOP and 1 to BR, n=2, 4%). Patient characteristics are summarized in the table below. Twenty-three patients (92%) in the low intensity group and 39 patients (95%) in the high intensity group had stage 4 at diagnosis. Twenty-one patients (84%) in the low intensity group and 37 patients (90%) in the high intensity group had bone marrow involvement. Three patients (12%) in the low intensity group required G-CSF plus plerixafor versus 13 patients (32%) in high intensity gr group for stem cell mobilization (p=0.1). Median day for neutrophil engraftment was 11 days in both groups, and median day for platelet engraftment was 12 days and 18 days in low intensity and high intensity regimen groups, respectively (P=0.001). Median follow-up of surviving patients was 4.18 and 4.93 years for low intensity and high intensity regimen, respectively. For low intensity regimen and high intensity regimen groups, 1-year OS was 95.7% and 97.4%, respectively (P=0.59); 1-year RFS was 92% and 89.6%, respectively (P=0.88); 1-year relapse rate was 4% and 10.4%, respectively (P=0.25); and 1-year NRM was 4% and 0%, respectively (P=0.15). Multivariable analysis identified that older age was associated with worse OS (HR 1.12, 95% CI 1.04-1.21, P=0.004), KPS < 80% was associated with higher NRM (HR 25.1, 95% CI 8.51-74.16, P Conclusion: Our data showed no significant difference in transplant outcomes for patients who achieve CR1 with low intensity regimens when compared to high intensity regimens. Patients who received high intensity induction regimen required plerixafor more frequently for stem cell mobilization, but no difference in neutrophil or platelet engraftment was noted in the two groups. Disclosures Modi: MorphoSys: Membership on an entity's Board of Directors or advisory committees. Deol:Kite, a Gilead Company: Consultancy; Novartis: Consultancy.

Introduction Autologous stem cell transplant (ASCT) as a salvage option in patients (pts) with late relapse (≥18 months after upfront ASCT) represents an effective therapy and can prolong response in Multiple Myeloma (MM). Presence of comorbidities such as renal dysfunction can limit treatment options and impact ASCT eligibility. Efficacy and safety data supporting a second ASCT in pts with renal dysfunction for relapsed disease are limited. Methods All adult pts with MM with renal dysfunction undergoing a non-tandem second ASCT at our institution between January 2006 and January 2019 were identified. Renal dysfunction was defined as pre-transplant creatinine clearance ≤ 60 ml/min. Demographics, disease characteristics, and treatment history were compiled. Relapse free survival (RFS), overall survival (OS), relapse rate, and non-relapse mortality (NRM) outcomes were assessed. RFS durations after both the first and second ASCTs for each pt were compared using a paired log-rank test and corresponding hazard ratios (HR) was estimated using a paired cox proportional hazards regression model through mixed-effects models. Results Thirty six pts with renal dysfunction underwent a second ASCT at our institution. Fourteen pts (39%) had progressive disease (PD) and 9 pts (25%) had very good partial response or better. Median time between first and second ASCT was 57.05 months (18.98-103.25). Conditioning regimens included: ≤140 mg/m2 Melphalan (MEL) (61%; n=22), >140 mg/m2 MEL (28%; n=10) and BEAM (8.3%; n=3). Median length of hospitalization during second ASCT was 18 days (Range, 11-74). Median time to granulocyte and platelet engraftment was 12 (9-16) and 19 (0-61) days, respectively. In hospital events included: treatment-requiring infections in 15 pts (41.7%) and cardiac complications in 5 pts (13.9%). Four pts (11.1%) required intensive/critical care admission. By day 100 (d100) assessment, 30 of 34 surviving pts (83% by ITT) had stable disease or better, and 4 pts (11%) had PD. Twenty pts (58.8%) had an improvement in disease status compared to their pre-ASCT status, while 8 pts (23.5%) maintained their pre-ASCT disease status. Five pts (14%) were readmitted by d100, with 2 pts requiring intensive care. One of 2 pts on dialysis pre-second ASCT became dialysis independent. From second ASCT, median RFS was 1.04 yrs (95% CI, 0.74 to 1.67) and median OS was 3.34 yrs (95% CI, 3.30 to 7.99; median follow up 4.31 yrs); respectively. The cumulative incidence rates for relapse and NRM at 1 yr after second ASCT were 37.1% and 5.6%, respectively. By MVA, light chain MM was associated with higher relapse rate (p=0.03) and lower NRM (p=0.01). Conclusion Our data suggests that second ASCT is well tolerated with low complication /readmission rates in patients with renal dysfunction. Second ASCT as salvage can provide disease control for more than a year for these patients who may have limited treatment options.

NCT01246206. The study was approved by Wayne State University Institutional Review Board.

Information on the use of hypomethylating agents (HMAs) as a pre-transplant cytoreductive therapy in MDS is limited. We retrospectively evaluated outcomes of 172 adult MDS patients, who underwent allogeneic hematopoietic stem cell transplantation between January 2000 and December 2016. Patients were divided into three groups: group 1 − pre-transplant blasts