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Background: Indefinite maintenance therapy after autologous stem cell transplant (ASCT) is the current standard of care in multiple myeloma (MM). However, in the real world, patients often discontinue treatment due to various reasons. In this study, we sought to analyze the effect of and reasons for early discontinuation of maintenance therapy on survival outcomes, studying patients who received less than 3 years of maintenance therapy (short-term maintenance group) or more than 3 years (continuous maintenance group). Methods: We retrospectively reviewed 340 patients who underwent ASCT from 2005-2016 and received maintenance therapy for at least six months without progression. The patients started maintenance therapy after 100 days of ASCT. Lenalidomide (89%) and bortezomib (10%) were the most commonly used agents for maintenance therapy. The primary endpoints included were progression-free survival (PFS) and overall survival (OS). All the endpoints were measured from the time of ASCT. The discontinuation was defined as permanently stopping the maintenance therapy. Patient, disease, and transplant-related characteristics were compared between the two groups using the Mann-Whitney U test for continuous variables, and chi-squared or Fisher's exact test for categorical variables. The probabilities of PFS and OS were calculated using the Kaplan-Meier (KM) method and compared using log-rank test. Results: One hundred and two (n= 102; 30%) patients discontinued maintenance therapy in the first 3 years (short-term maintenance group), while 238 patients remained on maintenance therapy for ≥ 3 years (continuous maintenance group). The groups had similar baseline characteristics in terms of age, gender, ISS staging, cytogenetics, response before ASCT, and melphalan dosing. About 20% of patients in both groups were older than 65 years. Among those alive at the last contact, the median follow up were 5.4 years and 6.1 years for the short-term and continuous maintenance therapy group, respectively. At the time of the last follow-up, 131/238 (55%) patients in the continuous maintenance group were still on maintenance therapy. The median PFS in the short-term maintenance group was 5.1 years (95% CI: 4.4-7.4) and median OS was 9.8 years (95% CI: 8.2- to NR), whereas in the continuous maintenance group both median PFS (95% CI: 8.5- NR) and OS were not reached. This latter group had significantly longer PFS and OS than the short-term maintenance group with a 5-year estimated PFS of 80% (95%CI: 74-85%) vs. 50% (95% CI: 39-60%) (p The most common reasons for early discontinuation of maintenance therapy (< 3 years) were adverse events related to maintenance therapy (58%). Four patient (4%) patients developed second primary malignancy (SPM) in this group. The most frequent hematological adverse events (AEs) were pancytopenia and isolated neutropenia. Fatigue and diarrhea were the most common non-hematological AEs. The reasons for stopping maintenance in the continued maintenance group were disease progression (24%) and adverse events (14%), while five patients (2%) developed SPM. Conclusion: In our institutional experience, 30 percent of MM patients discontinued maintenance therapy within 3 years of ASCT due to AEs or patient preference. These patients had inferior PFS and OS after ASCT compared to patients on continuous maintenance. Therefore, continuation of maintenance therapy should be strongly encouraged as safely possible and strategies like dose reduction or switching therapy are recommended. Figure 1 Figure 1. Disclosures Bumma: Janssen: Membership on an entity's Board of Directors or advisory committees; Amgen: Speakers Bureau; Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Background Systemic light chain (AL) amyloidosis is a clonal plasma‐cell neoplasm that carries a poor prognosis. Although AL amyloidosis and Multiple Myeloma (MM) can co‐exist and share various cytogenetic chromosomal abnormalities, little is known about Fluorescent in situ hybridization (FISH) and its prognostic relevance in AL amyloidosis. Aim: The study aims to evaluate the most prevalent FISH cytogenetic abnormalities in AL patients as independent prognostic factors, and assess the impact of cytogenetics on the survival of high‐risk cardiac AL patients. Materials & Methods This retrospective study reviewed 113 consecutive AL patients treated at The Ohio State University (OSU). Patients were divided into subgroups based on FISH data obtained within 90 days of diagnosis. Hyperdiploidy was defined as trisomies of at least 2 chromosomal loci. Primary endpoints were progression free survival (PFS) and overall survival (OS). Kaplan Meier curves were used to calculate PFS and OS. The log‐rank test and Cox proportional hazard models were used to test the equality of survival functions and further evaluate the differences between groups. Results FISH abnormalities were detected in 76% of patients. Patients with abnormal FISH trended toward lower overall survival (OS) (p=0.06) and progression free survival (PFS) (p=0.06). The two most prevalent aberrations were translocation t(11;14) (39%) and hyperdiploidy‐overall (38%). Hyperdiploidy‐overall was associated with worsening PFS (p=0.018) and OS (p=0.03), confirmed in multivariable analysis. Patients with del 13q most frequently had cardiac involvement (p=0.006) and was associated with increased bone marrow plasmacytosis (p=0.02). Cardiac AL patients with no FISH abnormalities had much improved OS (p=0.012) and PFS (p=0.018) Conclusions Our findings ultimately reveal the association of hyperdiploidy on survival in AL amyloidosis patients, including the high‐risk cardiac AL population., Hyperdiploidy in AL amyloidosis patients was associated with poor PFS and OS and cardiac AL patients had a strong association with del 13q.

Autologous stem cell transplant (ASCT) is the standard of care for patients with multiple myeloma (MM). The clinical significance of peripheral blood T lymphocyte (PBTL) immunologic changes associated with ASCT is poorly understood. Here we evaluated T cell transcriptional messenger RNA profiles and immunophenotypes to correlate immunologic senescence, exhaustion, and anergy with clinical endpoints in a cohort of patients with MM undergoing ASCT. ASCT induced global transcriptional T cell changes and altered molecular levels of markers of T cell subtypes, T cell activation, and exhaustion. These included reduced CD4/CD8 ratio, skewing toward the Th1 subset, reduced expression of costimulatory receptors CD27 and CD28, heightened T cell activation, and increased expression of immune modulatory molecules LAG3 and PD1. Multicolor flow cytometry experiments confirmed altered circulating CD4 and CD8 subsets and skewing toward differentiated effector cells. Moreover, ASCT promoted an exhausted immunophenotype in CD3+CD4+ subsets and a senescent immunophenotype in CD3+CD8+ subsets. Subset-specific altered expression was also seen for surface molecules with immunomodulatory function. ASCT affected soluble levels of molecules with immunomodulatory function by increasing plasma HVEM and TIM3. High molecular LAG3 level was associated with inferior event-free survival post-ASCT (hazard ratio=5.44; confidence interval, 1.92 to 15.46; P = .001; adjusted P [controlling for false discovery rate] = .038). Using a comprehensive evaluation of PBTLs on a molecular and phenotypic level, we have identified that ASCT induces global T cell alterations with CD4 and CD8 subset-specific changes. Moreover, LAG3 emerged as an early biomarker of adverse events post-ASCT. These findings will support the development of treatment strategies targeting immune defects in MM to augment or restore T cell responses.

Post-autologous stem cell transplantation (ASCT) maintenance therapy with lenalidomide is standard of care for patients with multiple myeloma (MM). Effective and tolerable drug combinations may further enhance the clinical response post-ASCT. Vorinostat, a histone deacetylase inhibitor, induces antiproliferative and proapoptotic effects in patients with MM. We hypothesized that combination maintenance therapy would further prolong the clinical response achieved from transplantation. We previously reported that the combination of lenalidomide and vorinostat as maintenance post-ASCT was tolerable in 16 patients with MM. We now present the long-term follow up of these patients. Progression-free survival (PFS) and overall survival (OS) outcomes were characterized using the Kaplan-Meier method. Five patients (31%) had high-risk disease, and the median number of lines of therapy before ASCT was 1 (range, 1 to 5). With a median follow-up of 89.8 months from ASCT, the median PFS was 64.3 months (range, 21.7 months to not reached [NR]), and OS was not reached (median, 53.0 months to NR). At the time of this report, 5 patients remained on the study. The combination of vorinostat and lenalidomide as maintenance post-ASCT is tolerable and induces a durable response. A phase III randomized study of lenalidomide versus a combination with vorinostat is warranted.

Allogeneic hematopoietic cell transplantation (allo-HCT) from a haploidentical (haplo) donor has emerged as a suitable alternative in the absence of a matched donor. However, haplo-HCT patients have a higher risk of graft-versus-host disease (GVHD). Hence, bone marrow (BM) stem cell source and post-transplant cyclophosphamide (PTCy) have been routinely used to help mitigate this. Due to ease of collection, peripheral blood (PB) stem cells are increasingly being considered for haplo-HCT. We retrospectively analyzed 74 patients (42 BM and 32 PB) who underwent haplo-HCT at Ohio State University from 2009 to 2018. Median age at transplant was 60 years (yrs) for BM and 54 yrs for PB, (p = 0.45). There was no difference in OS (p = 0.13) and NRM (p = 0.75) as well as PFS (p = 0.10) or GRFS (p = 0.90) between the groups. The BM cohort showed a 3-year OS rate of 63% (95% confidence interval (CI): 46–76), and 3-year PFS of 49% (95% CI: 33–63). For the PB group, 3-year OS and PFS were 78% (95% CI: 59–89) and 68% (95% CI: 49–82), respectively. There were no differences in the incidence of acute GVHD (grade II-IV) (p = 0.31) and chronic GVHD (p = 0.18). Patients receiving BM had a significantly higher risk for relapse with relapse rates by 2 years at 36% (95% CI: 22–50) vs. 16% (95% CI: 6–31) for PB (p = 0.03). The findings from this study suggest that PB is an excellent alternative to BM for haplo-HCT.

Acute graft versus host disease (aGVHD) remains a leading cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HSCT). Tacrolimus (TAC), a calcineurin inhibitor that prevents T-cell activation, is commonly used as a GVHD prophylaxis. However, there is variability in the serum concentrations of TAC, and little is known on the impact of early TAC levels on aGVHD. We retrospectively analyzed 673 consecutive patients undergoing allo-HSCT at the Ohio State University between 2002 and 2016. Week 1 TAC was associated with a lower risk of aGVHD II–IV at TAC level ≥ 10.15 ng/mL (p = 0.03) compared to the lowest quartile. The cumulative incidence of relapse at 1, 3 and 5 years was 33%, 38% and 41%, respectively. TAC levels at week 2, ≥ 11.55 ng/mL, were associated with an increased risk of relapse (p = 0.01) compared to the lowest quartile. Subset analysis with acute myeloid leukemia and myelodysplastic syndrome patients showed significantly reduced aGVHD with TAC level ≥ 10.15 ng/mL at week 1 and a higher risk of relapse associated with week 2 TAC level ≥11.55 ng/mL (p = 0.02). Hence, achieving ≥10 ng/mL during the first week of HCT may mitigate the risk of aGVHD. However, levels (&gt, 11 ng/mL) beyond the first week may be associated with suppressed graft versus tumor effect and higher relapse.

Multiple myeloma (MM) is an incurable disease with a limited life expectancy of five years from diagnosis. Uncontrolled disease or infections are the main causes of mortality. Daratumumab, a monoclonal antibody against CD38, is approved to treat patients with MM. Its target, CD38, is expressed not only on MM cells but also on common lymphoid precursors and subsets of normal lymphocytes. Daratumumab-induced lymphopenia is common, but its clinical significance is understudied. In this study, we report the baseline characteristics, rates of severe lymphopenia, infections, and clinical trajectory of multiple myeloma patients (n = 100) treated with daratumumab-based regimens at the Ohio State University Comprehensive Cancer Center. We discover high rates of infections, hospital utilization, and severe lymphopenia and identify risks factors for severe lymphopenia, such as low pretreatment absolute lymphocyte count (ALC) values. Severe lymphopenia persists in 23% of patients, resulting in worst survival outcomes. Our data underline the importance of monitoring ALC and consider future use of prophylactic measures or alternative regimens in subsets of MM patients.

Multiple myeloma (MM) and Waldenström's macroglobulinemia (WM) are plasma cell disorders often treated with proteasome inhibitors. Recently, several studies evaluated carfilzomib as an initial treatment for these diseases and reported outstanding clinical outcomes. We conducted a retrospective study to report the efficacy and safety of frontline carfilzomib-based combinations in a standard of care setting. From 2014 until 2016 we identified newly diagnosed MM (n = 54) and WM (n = 6) patients treated with carfilzomib as initial therapy who met study inclusion criteria. The response rate for myeloma patients was 98% with 77% of patients undergoing upfront autologous stem cell transplant. The clinical benefit for WM was 100% with all patients having a resolution of B symptoms and anemia after treatment. Carfilzomib-based regimens are well tolerated and offer a neuropathy sparing approach with excellent responses both in newly diagnosed MM and WM making them a good choice for the frontline treatment of these diseases.

Heavy chain disorders are rare B-cell disorders and include heavy chain disease, heavy chain deposition disease, and heavy chain amyloidosis. These disorders share the pathognomonic finding of a truncated immunoglobulin heavy chain without an associated light chain in the serum or urine in the case of heavy chain disease or in the tissues in the case of heavy chain deposition disease and heavy chain amyloidosis but are clinically distinct entities. The clinical recognition and systematic approaches to these disorders are challenging because of the rarity of the diseases, lack of consensus on treatment approaches, and minimal data with novel therapy. Herein we present a review of the literature and 5 consecutive cases at a single institution of gamma heavy chain disease and heavy chain deposition disease treated with novel agents including regimens of CRd (cyclophosphamide, lenalidomide, and dexamethasone), CyBorD (cyclophosphamide, bortezomib, and dexamethasone), R-CVP (rituximab, cyclophosphamide, vincristine, and dexamethasone), BR (bendamustine and rituximab), V-EPOCH (bortezomib, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin), and autologous hematopoietic stem cell transplantation.

Background: Modakafusp alfa (previously known as TAK-573) is a first-in-class immunocytokine designed to deliver interferon alpha-2b (IFNα2b) to CD38+ cells. It consists of two attenuated IFNα2b molecules genetically fused to the Fc portion of a humanized, anti-CD38, IgG4 monoclonal antibody (mAb). The specificity for CD38 and reduced IFN receptor binding affinity of the attenuated IFNα2b molecules significantly reduces the potential for off-target binding and toxicity. Furthermore, modakafusp alfa binds to a different epitope on CD38 than the currently approved anti-CD38 therapeutic mAbs, daratumumab and isatuximab. Preclinical evaluation of modakafusp alfa supports activation of type I IFN signaling in CD38+ cells, inducing direct anti-proliferative effects on myeloma cells, as well as direct and indirect immune cell activation. We have previously reported preliminary results from the first 59 patients (pts) in our first-in-human phase 1 trial of modakafusp alfa in pts with relapsed/refractory multiple myeloma (RRMM; NCT03215030), showing responses to single-agent therapy with doses starting at 0.1 mg/kg weekly; thrombocytopenia and neutropenia were dose-limiting toxicities when modakafusp alfa was administered weekly (QW), every 2 weeks (Q2W), and every 3 weeks (Q3W) (Vogl, Blood 2020). Here we report updated results from this trial, focusing on results from an expansion cohort with dosing every 4 weeks (Q4W). Methods: Eligible pts with RRMM who had received at least three previous lines of treatment received modakafusp alfa as a 1- to 4-hour intravenous infusion at 11 dose levels from 0.001 to 6 mg/kg following a 3+3 dose-escalation design. The initial dosing schedule was QW for 8 doses, then Q2W for 8 doses, and then monthly; subsequent cohorts evaluated dosing Q2W, Q3W or Q4W. Expansion cohorts were planned using modakafusp alfa at protocol-defined, biologically active doses that did not exceed the maximum tolerated dose (MTD). Results: As of May 2021, 83 pts had been treated across all planned dosing schedules. With Q4W dosing, the MTD was exceeded at the 6 mg/kg dose due to DLTs: a grade 3 infusion reaction and prolonged thrombocytopenia and neutropenia, which delayed the start of cycle 2 by >14 days. In total, 24 pts were treated with 1.5 mg/kg modakafusp alfa Q4W (5 pts during dose escalation and 19 pts in an expansion cohort). Analyses include data from all 24 pts. The median number of prior lines of therapy received was 6 (range 4-16); 21 pts (88%) were refractory to an anti-CD38 mAb, and 20 (83%) were triple class-refractory (to a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 mAb). Grade 3 or higher treatment-emergent adverse events (TEAEs) were reported in 18 pts (75%). The most frequent grade 3-4 TEAEs were neutropenia in 12 pts (50%; grade 4 in 6 [25%]), leukopenia in 9 (38%), decreased lymphocyte count in 9 (38%), anemia in 8 (33%), and thrombocytopenia in 8 (33%; grade 4 in 3 [13%]). One pt (4%) had a grade 3 bleeding event and continues on study treatment; 3 pts (13%) had infections (grade 3 in 2 [8%]); and 8 (33%) had infusion reactions (grade 3 in 1 [4%]). The overall response rate (ORR, ≥partial response [PR]) was 42% (complete response [CR], n=2; very good partial response [VGPR], n=5; PR, n=3), and the clinical benefit rate (ORR + minimal response [MR]) was 54% (MR, n=3). Median progression-free survival was 5.7 months (95% confidence interval [CI], 1.9-not reached [NR]), median time to response was 1.9 months (95% CI, 0.95-NR), and median duration of response was 7.4 months (95% CI, 2.3-NR). Among the 21 anti-CD38 mAb-refractory pts, the ORR was 43%, while among the 4 pts who received an anti-CD38 mAb in their most recent line of therapy prior to enrollment, the ORR was 75% (CR, n=1; VGPR, n=2). Correlative studies show evidence of T-cell and natural killer-cell activation, as well as activation of IFN signaling in CD38+ cells, including upregulation of CD38 expression. Conclusion: Modakafusp alfa (TAK-573) is a novel candidate for the treatment of RRMM, which has shown promising anti-myeloma activity in heavily pretreated pts, including anti-CD38 mAb-refractory pts and those who have received an anti-CD38 mAb in their most recent line of treatment. A Q4W dosing schedule of modakafusp alfa is feasible and the optimal dose and potential combinations are being explored. Disclosures Vogl: Takeda: Consultancy, Research Funding; Karyopharm: Consultancy; GSK: Consultancy; Oncopeptides: Consultancy; Janssen: Consultancy; Sanofi: Consultancy; CSL Behring: Consultancy; Active Biotech: Research Funding. Kaufman: Genentech, AbbVie, Janssen: Consultancy, Research Funding; Amgen: Research Funding; Janssen: Honoraria; Roche/Genetech, Tecnopharma: Consultancy, Honoraria; Fortis Therapeutics: Research Funding; Novartis: Research Funding; Incyte, celgene: Consultancy; Sutro, Takeda: Research Funding; Tecnofarma SAS, AbbVie: Honoraria; BMS: Consultancy, Research Funding; Incyte, TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; Heidelberg Pharma: Research Funding. Holstein: Oncopeptides: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech, GSK, Janssen, Secura Bio, Sorrento: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Atrash: AMGEN: Research Funding; Jansen: Research Funding, Speakers Bureau; GSK: Research Funding. Nadeem: Takeda: Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees. Janakiram: Kyowa Kirin Therapeutics: Honoraria; Takeda Pharmaceuticals: Research Funding; FATE Therapeutics: Research Funding; ADC Therapeutics: Research Funding. Suryanarayan: Takeda: Current Employment. Liu: Takeda: Current Employment. Parot: Takeda Pharmaceuticals: Current Employment. OffLabel Disclosure: Modakafusp alfa (TAK-573) is a first-in-class immunocytokine consisting of 2 attenuated interferon alpha-2b molecules genetically fused to an anti-CD38, IgG4 monoclonal antibody. This abstract contains information about investigational use of modakafusp alfa in patients with relapsed/refractory multiple myeloma. Safety and efficacy have not been determined.

Introduction: Sporadic cases of patients with a combined T-cell malignancy and plasma cell dyscrasia (PCD) have been reported in the literature. While the most commonly observed association is with T-cell large granular lymphocytic leukemia (T-LGLL) and PCD, there are case reports of other T-cell malignancies and PCD, such as peripheral T-cell lymphoma (PTCL) and angioimmunoblastic T-cell lymphoma (AITL) with multiple myeloma (MM). Nearly one-third of MM patients develop clonal T-cell populations that share a similar immunophenotype to T-LGLL, suggesting likely under diagnosis of concomitant T-cell malignancies in patients with PCD. However, with the limited data available regarding the overlap between PCD and T-cell malignancy, the significance, associated pathogenesis, and impact on survival outcomes is unknown. The purpose of this study is to describe the outcomes of patients with overlapping T-cell malignancies and PCD in order to determine the survival outcomes and ultimately make management/diagnostic recommendations. Methods: In this IRB approved study, we retrospectively evaluated patients with concomitant T-cell malignancy and PCD at Ohio State University from 2010-2020. Patients were identified using a database search for T-cell malignancies as well as PCD. All patients that were included met the 2016 World Health Organization diagnostic criteria for their respective T-cell malignancy and PCD. Progression-free survival (PFS) was measured as time from the start of treatment until first progression, death, or last follow-up according to the Kaplan-Meier method with median survival times and 95% confidence intervals reported. Results: A total of 21 patients, with a median follow-up time of 22 months (range 1-153), were included in this analysis. Baseline demographics are in table 1. The most common T-cell malignancy was T-LGLL (11/21; 52%) and the most common PCD were MGUS (8/21; 38%) and MM (8/21; 38%). Ten (48%) patients presented with a T-cell malignancy as their primary malignancy, 9 (43%) presented with a PCD as their primary malignancy, 1 (5%) patient was diagnosed with both at the same time, and for 1 (5%) patient it is unknown. Within the cohort, 62% (13/21) of patients received primary treatment for their T-cell malignancy and 38% (8/21) of patients received primary treatment for their PCD. Of the 7 patients that had their PCD clone 4 were treated concomitantly and 3 were treated for only their T-cell malignancy. Overall, 9/21 (42.9%) of patients had progression of their T-cell malignancy. A summary of outcomes is provided in Table 2. 54.6% of patients with T-LGLL and 60% of patients with AITL/PTCL experienced progressive T-cell disease and no patients with CTCL had progressive T-cell disease. The median overall survival (OS) across all patients was 4.1 years. Median OS was not reached for patients with T-LGLL, 1.7 years for AITL/PTCL, and 12.4 years for CTCL. PFS was 11 months for patients with T-LGLL, 1 year for AITL/PTCL, and 12.37 years for CTCL. Survival probability is shown in Figure 1. The rates of progression, OS, and PFS were consistent with previously published data for patients with these T-cell malignancies. Conclusions: Herein, we characterize a cohort of patients with concomitant T-cell malignancies and PCD with an emphasis on survival outcomes. Our data suggests that there is no PFS or OS difference for patients with T-cell malignancies and concomitant PCD when treated with standard T-cell directed therapy. There is the potential that treating a patient's T-cell malignancy may lead to resolution of their PCD clone, even without therapy directed at the PCD. While our data is limited by small sample size, this report represents the largest data set available in this rarely described patient population. Larger retrospective cohort studies are needed to further characterize this population and validate these findings. For patients with T-cell malignancies as the primary diagnosis with concomitant PCD, treatment with standard T-cell directed therapies is recommended with continued follow-up and monitoring of the concomitant PCD. Figure 1 Figure 1. Disclosures Bumma: Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees. Porcu: Viracta: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Innate Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BeiGene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; Daiichi: Honoraria, Research Funding; Kiowa: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Spectrum: Consultancy; DrenBio: Consultancy. Brammer: Seattle Genetics: Speakers Bureau; Celgene: Research Funding; Kymera Therapeutics: Consultancy.

Background: Allogeneic stem cell transplantation (allo-SCT) has become an increasingly important consolidation treatment option for patients with acute myeloid leukemia (AML) and as upfront therapy for patients with high-risk myelodysplastic syndrome (MDS). Although the median age at diagnosis for both diseases is above 65 years, studies evaluating allo-SCT as treatment option for patients aged 65 years or older are limited. Further, as the population ages, the number of patients above 65 years considered for allo-SCT will continue to rise. Thus, the aim of our current investigation was to analyze outcomes based on age in AML/MDS patients Methods: A retrospective analysis was performed for all AML/MDS patients who received allo-SCT between January 1984 and December 2018 at our institution. Primary endpoints included progression free survival (PFS) and overall survival (OS). PFS was counted from the day of transplantation to relapse or death. OS was defined as survival from the day of allo-SCT until death from any cause, with censoring of patients known to be alive at the time of last follow-up. PFS and OS were calculated using Kaplan Meier Curves. Secondary endpoints included cumulative incidences of grade II-IV and III-IV acute GVHD (aGVHD), chronic GVHD (cGVHD), relapse, and non-relapse mortality (NRM). Cumulative incidence rates of aGVHD, cGVHD, relapse, NRM were estimated and compared using Gray's test accounting for competing risks. Results: The cohort consisted of 900 AML/MDS patients, with 150 patients ≥65 years and 750 patients The median time from diagnosis to transplantation was 176 days (range: 55-4920) for age Conclusion: Overall, our study suggests similar outcomes for elderly patients undergoing allo-HCT as compared to their counterparts, which is in line with prior studies. This likely is due to advancements in the transplant field, including the development of RIC and alternative donors, which have allowed greater access to transplant for older adults. Utilization of allo-HCT is feasible and should be considered for AML/MDS patients ≥65 years. Further research is underway to evaluate the important determinants of health status in older patients undergoing allo-HCT and to ultimately help predict NRM (BMT CTN 1704). Figure 1 Figure 1. Disclosures Bumma: Amgen, Sanofi: Speakers Bureau; Janssen, Oncopeptides, Sanofi: Consultancy. Vasu: Seattle Genetics: Other: travel support; Boehringer Ingelheim: Other: Travel support; Kiadis, Inc.: Research Funding; Omeros, Inc.: Membership on an entity's Board of Directors or advisory committees. Jaglowski: Takeda: Consultancy; Juno: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding; CRISPR Therapeutics: Consultancy; Novartis: Consultancy, Research Funding. Mims: Syndax Pharmaceuticals: Consultancy; BMS: Consultancy; Jazz Pharmaceuticals: Consultancy; Abbvie: Consultancy; Genentech: Consultancy; Kura Oncology: Consultancy; Leukemia and Lymphoma Society: Consultancy; Glycomemetics: Research Funding; Aptevo: Research Funding; Xencor: Research Funding; Daiichi-Saynko: Consultancy. Brammer: Celgene: Research Funding; Seattle Genetics: Speakers Bureau; Kymera Therapeutics: Consultancy. Saad: Incyte Pharmaceuticals: Consultancy; careDx: Consultancy; Amgen: Research Funding; Kadmon: Research Funding; OrcaBio: Research Funding; Magenta Therapeutics: Consultancy. de Lima: Miltenyi Biotec: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees.

Introduction: Allogeneic hematopoietic stem cell transplant (allo-HCT) is a potential curative therapy for a variety of both malignant and nonmalignant hematologic disorders. However, allo-HCT is costly and requires highly specialized, technologically advanced care that is only available in select healthcare centers across the country. Due to its cost and limited availability, minority populations are at risk for healthcare disparities in access to and outcomes of allo-HCT. Prior studies have focused on the impact of health disparities, including race, and geographic residence at time of transplant, on allo-HCT outcomes with variable results. The aim of this study was to evaluate the impact of race and location of residence on outcomes of allo-HCT at one major referral institution. Methods: We performed a retrospective cohort study of patients that underwent allo-HCT at the Ohio State University from 1984 to 2018. The impact of demographic factors including race and place of primary residence were assessed. Patients were divided into race defined as Caucasian, African American (AA), and other. They were also grouped by zip code into rural, suburban, and urban groups. Rural was defined as less than 1000 people per square mile, suburban between 1000-3000 people per square mile, and urban greater than 3000 people per square mile. 2018 population estimates were used. Patients were then stratified into 7 groups based on year (yr) of transplant for analysis. Group (gp) 1 included 1984-1988, gp 2 1989-1993, gp 3 1994-1998, gp 4 1999-2003, gp 5 2004-2008, gp 6 2009-2013, and gp 7 2014-2018. Primary endpoints were progression free survival (PFS) and overall survival (OS). PFS and OS were calculated using Kaplan Meier Curves and compared using log-rank test between race and residence groups. Results: A total of 1,943 patients were included in the study. Of these patients, median age at time of transplant was 50 years old (range 18-76), and 59.6% were male. AML/MDS patients made up the majority of the cohort at 46.3%, with the other most common diagnoses being non-Hodgkin's lymphoma (14.2%), acute lymphocytic leukemia (11.8%), and chronic myeloid leukemia (10.1%). Most patients (94.3%) identified as Caucasian, while 4.6% identified as AA, and 1.1% other. The majority of patients lived in a rural area at the time of transplant with 63.4% rural, 22.9% suburban, and 13.8% urban. There was no significant difference in OS or PFS between Caucasian and AA patients (Figure 1A and B; p=0.15, 0.21). Median OS for AA was 1.9 yrs [95% confidence interval (CI): 0.8-3.6] as compared to 2.3 yrs (95% CI: 1.9-2.9) for Caucasians, with 5 -yr OS of 33 vs. 42% and 10-yr OS of 21 vs. 36% for AA and Caucasian, respectively. Median PFS was 0.9 (95% CI: 0.5-2.7) and 1.3 yrs (95% CI 1.1-1.6), with 5 -yr PFS of 30 vs. 37% and 10-yr PFS of 21 vs. 32% for AA and Caucasian, respectively. There also was no significant difference in OS or PFS between rural, urban, and suburban patients (Figure 2A and 2B; p=0.39, 0.17), with median OS in the three groups 2.2 (95%CI: 1.7-2.9), 2.9 (95%CI: 1.6-4.5), and 2.2 (95% CI: 1.6-3.6) yrs, and 5-yr OS of 40 vs. 43 vs. 43% and 10-yr OS of 33 vs. 39 vs. 39%, respectively. Median PFS were 2.2 (95%CI: 1.7-2.9), 2.9 (95%CI: 1.6-4.5), and 2.2 yrs [95% CI: 1.6-3.6], with 5-yr PFS of 36 vs. 40 vs. 38% and 10-yr PFS of 30 vs. 37 vs. 35%, respectively. Conclusion: Our study suggests that once patients undergo allo-HCT, there is no significant difference in outcomes between patients based on race or residence. This finding suggests that while these underserved populations may initially have less access to specialized care for HCT, if they ultimately undergo allo-HCT, outcomes are similar to their counterparts. Our study did show a significantly lower rates of allo-HCT performed in non-Caucasian races (94% Caucasians vs 4.6% AA and 1% other), which may reflect disparities in access to care in these groups as well as a lack of donors. Further research is needed to assess the barriers for these underserved patients to undergo transplant and to help ameliorate these barriers. Disclosures Chaudhry: Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees. Bumma:Amgen: Speakers Bureau; Sanofi: Speakers Bureau. Khan:Amgen: Consultancy; Janssen: Consultancy. Devarakonda:Janssen: Consultancy. Vasu:Janssen: Membership on an entity's Board of Directors or advisory committees; Omeros: 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. Jaglowski:Kite, a Gilead Company: Consultancy, Research Funding; Juno: Consultancy; Novartis: Consultancy, Research Funding; CRISPR: Consultancy. William:Merck: Research Funding; Celgene: Consultancy, Honoraria; Dova: Research Funding; Seattle Genetics: Research Funding; Incyte: Research Funding; Guidepoint Global: Consultancy; Kyowa Kirin: Consultancy, Honoraria. Mims:Syndax Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Kura Oncology: Membership on an entity's Board of Directors or advisory committees; Leukemia and Lymphoma Society: Other: Senior Medical Director for Beat AML Study; Agios: Consultancy; Novartis: Speakers Bureau; Jazz Pharmaceuticals: Other: Data Safety Monitoring Board. Brammer:Seattle Genetics, Inc.: Speakers Bureau; Celgene Corporation: Research Funding. Efebera:Celgene: Research Funding; Pharmacyclics: Research Funding; Takeda: Honoraria, Speakers Bureau; Ohio State University: Current Employment.

Background: Allogeneic transplantation (allo-HCT) is a potentially curative treatment for a variety of hematologic malignancies and nonmalignant hematologic disorders. Allo-HCT from a haploidentical (Haplo) related donor has emerged as a suitable alternative in the absence of matched related donor (MRD) and matched unrelated donor (MUD). Haplo HCT patients however have higher risk of graft rejection and graft versus-host disease (GVHD). Thus, patients often receive post-transplant cyclophosphamide (PTCy), which has proven to be highly effective in reducing GVHD. While the use of peripheral blood is an attractive option due to the ease of collection and rapid peripheral blood count recovery, not much information is available on the impact of graft sources using PTCy in Haplo-HCT. This study compares outcomes of bone marrow (BM) versus peripheral blood (PB) stem cell graft for Haplo-HCT in adult patients. Methods: We performed a retrospective study of 81 adult patients who underwent Haplo-HCT at The Ohio State University from 2009 to 2018. The study endpoints were overall survival (OS), progression free survival (PFS), non-relapse mortality (NRM), relapse, engraftment, acute GVHD (grade II-IV), and chronic GVHD. All endpoints were measured from the time of transplantation. Patient, disease, and transplant-related characteristics were compared between the two groups (BM versus PB) using the Mann-Whitney U test for continuous variables, and chi-squared or Fisher's exact test for categorical variables. The probabilities of OS and PFS were calculated using the Kaplan-Meier (KM) method and compared using log-rank test. Cumulative incidence rates were estimated and compared using Gray's test accounting for competing risks. Results: We compared the outcomes of patients who received a BM graft (N=43) with those receiving a PB graft (N=38). The median age at transplant was 57 years (20-74). All patients received PTCy in addition to tacrolimus and mycophenolate in 91% of patients. Reduced intensity conditioning (RIC) was used in majority of patients (N=63, 78%). The two groups were comparable including age (median, 60 years for BM and 56 years for PB, p=0.60) and the type of conditioning regimen (79% RIC for BM, 76% RIC for PB, p=0.77). The number of CD34+ and CD3+ infused cells was higher in PB grafts (median, 8.6x106 CD34+ cells/Kg, 2.0 x108 CD3+ cells/Kg, respectively) than for BM (median, 3.7x106 CD34+cells/Kg, 0.4x108 CD3+cells/Kg, respectively). Time to neutrophil and platelet engraftment were significantly shorter in patients receiving PB versus those getting BM grafts: median 15 vs. 17.5 days, (p=0.02) and median 20 vs. 29 days (p Conclusion: Our study suggests peripheral blood for haploidentical transplant to be a good alternative to bone marrow. Similar PFS, OS and NRM were seen between the two graft sources. As expected, faster neutrophil and platelets engraftment were seen with PB due to more CD3+ and CD34+ infused, but without an increase in acute or chronic GVHD. A reduced relapse risk was observed with PB graft. Our study is small and is retrospective, but provide encouraging results. A prospective randomized controlled trial is required to confirm these results. Disclosures Chaudhry: Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees. Bumma:Sanofi: Speakers Bureau; Amgen: Speakers Bureau. Khan:Amgen: Consultancy; Janssen: Consultancy. Devarakonda:Janssen: Consultancy. Vasu:Kiadis Inc: Other: Kiadis has obtained exclusive licensing requirements from The OHio State University; Janssen: Membership on an entity's Board of Directors or advisory committees; Omeros: Membership on an entity's Board of Directors or advisory committees. Jaglowski:Novartis: Consultancy, Research Funding; Juno: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding; CRISPR: Consultancy. William:Seattle Genetics: Research Funding; Merck: Research Funding; Dova: Research Funding; Kyowa Kirin: Consultancy, Honoraria; Guidepoint Global: Consultancy; Incyte: Research Funding; Celgene: Consultancy, Honoraria. Mims:Jazz Pharmaceuticals: Other: Data Safety Monitoring Board; Abbvie: Membership on an entity's Board of Directors or advisory committees; Syndax Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Kura Oncology: Membership on an entity's Board of Directors or advisory committees; Leukemia and Lymphoma Society: Other: Senior Medical Director for Beat AML Study; Agios: Consultancy; Novartis: Speakers Bureau. Brammer:Bristol-Myers Squibb: Research Funding; Celgene: Research Funding; Seattle Genetics: Honoraria, Speakers Bureau; Kymera: Honoraria; Verastem Oncology: Other: Travel. Saad:Amgen: Other: research support; Magenta Therapeutics: Other: Personal Fees; Incyte Pharmaceuticals: Other: Personal Fees; Orcabio: Other: research support; Kadmon: Other: research support. Efebera:Celgene: Research Funding; Ohio State University: Current Employment; Takeda: Honoraria, Speakers Bureau; Pharmacyclics: Research Funding.

B ackground Premature death from opioid-related causes imposes an enormous public health burden across the United States. Between 2001 and 2016, the number of opioid-related deaths in the United States increased by 345%, from 9489 to 42 245 deaths (33.3 to 130.7 deaths per million population. Moreover, opioids may have immunosuppressive properties independent of their psychotropic effects; opioid use has been associated with increased invasive pneumococcal disease in a nested case-control study of 1233 Medicaid patients from Tennessee. In liver transplant recipients, opioid use disorder has been associated with increased mortality after transplant. The impact of opioid use disorder on patients receiving blood and marrow transplant (BMT) remains to be defined. Methods We performed a retrospective analysis of all consecutive adult patients who had BMT (autologous and allogeneic) from 1/1/2008 through 1/1/2018 at the James Comprehensive Cancer Center. Overall survival (OS) was measured from the date of transplant to the date of death, censoring at date of last follow up if alive. Progression free survival (PFS) was measured from the date of transplant to the date of disease progression or the date of death, whichever occurred first, censoring at last follow up if no event. OS and PFS were estimated by the Kaplan-Meier method and compared using the log-rank test. Opioid use (OU) was defined as a binary yes/no variable if an opioid was prescribed upon discharge from the hospital after BMT. The impact of OU, along with other patient, disease, and BMT related factors, on PFS/OS, was analyzed using Cox regression method. Results A total of 1585 patients were included in the analysis (Table 1). The median age at BMT was 58 (range=18-79) years; 59% were males; 60% had autologous transplants; and 58% were prescribed opioids upon discharge from the hospital. OU was significantly more in patients who were younger, have had allogeneic transplant, reduced intensity conditioning, had acute myeloid leukemia (AML), or higher BMT comorbidity index (CMI). On univariable analysis, OU was not associated with cumulative incidence of relapse (CIR) or PFS however it was associated with inferior OS; hazard ratio (HR)=1.25, 95% CI: 1.06-1.49; p=0.01 (Figure-1). There were no differences in CIR, PFS, or OS when autologous and allogeneic transplants were analyzed separately. Upon multivariable analysis of OS, OU lost statistical significance after controlling for age, diagnosis, type of transplant, intensity of conditioning regimen, CMI, and disease risk index (DRE). Of interest, OU independently predicted for superior OS at 100 days and 365 days post-BMT; HR=0.29, 95% CI 0.16-0.50 (p= Conclusion: Our results suggest that opioid use (OU) may have a long term negative impact on survival in BMT patients. The apparently protective effects of OU early on after BMT is elusive but may be possibly related immunomodulatory effects of opioids. A major limitation of our study is that OU is analyzed at a single time point at hospital discharge after BMT. We plan to undertake a more detailed analysis of ongoing OU after discharge and its impact on survival outcomes after BMT. Disclosures Brammer: Celgene Corporation: Research Funding; Seattle Genetics, Inc.: Speakers Bureau. Efebera:Celgene: Research Funding; Ohio State University: Current Employment; Pharmacyclics: Research Funding; Takeda: Honoraria, Speakers Bureau. Mims:Abbvie: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Other: Data Safety Monitoring Board; Syndax Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Kura Oncology: Membership on an entity's Board of Directors or advisory committees; Leukemia and Lymphoma Society: Other: Senior Medical Director for Beat AML Study; Agios: Consultancy; Novartis: Speakers Bureau. Chaudhry:Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees. Bumma:Sanofi: Speakers Bureau; Amgen: Speakers Bureau. Khan:Amgen: Consultancy; Janssen: Consultancy. Devarakonda:Janssen: Consultancy. Jaglowski:Novartis: Consultancy, Research Funding; CRISPR: Consultancy; Juno: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding. William:Kyowa Kirin: Consultancy, Honoraria; Merck: Research Funding; Seattle Genetics: Research Funding; Incyte: Research Funding; Guidepoint Global: Consultancy; Dova: Research Funding; Celgene: Consultancy, Honoraria.

Background: TAK-573 is a first-in-class, humanized, anti-CD38, IgG4 monoclonal antibody genetically fused to 2 attenuated interferon alpha-2b (IFNα2b) molecules. The specificity for CD38 and reduced binding affinity of the attenuated IFNα molecules significantly reduces the potential for off-target toxicity. TAK-573 binds to a site on CD38 that is distinct from the binding sites of currently available therapeutic antibodies, and therefore does not compete for binding with daratumumab or isatuximab. Non-clinical studies have shown that TAK-573 has robust anti-tumor activity, including complete responses, in MM xenograft models. Patients and Methods: The first in human phase I trial (NCT03215030) enrolled patients (pts) with relapsed or refractory multiple myeloma (RRMM) after at least 3 previous lines of treatment. Pts received TAK-573 as a 1 to 4-hour IV infusion in 11 dose levels from 0.001 to 3 mg/kg. The initial schedule was weekly for 8 doses, then every 2 weeks for 8 doses, and then monthly. Subsequent cohorts are also exploring dosing once every 2 (Q2), every 3 (Q3) or every 4 weeks (Q4). Peripheral blood (PB) and bone marrow (BM) aspirates were collected before and after TAK-573 dosing. CD38 receptor occupancy (RO) and receptor density (RD) were determined using 9-color flow cytometry. Serum samples were analyzed using the Immuno-Oncology panel of Olink's proximity extension assay platform to measure changes in cytokine and chemokine levels. Whole transcriptome sequencing of bulk RNA was performed to determine the type I interferon (IFN) gene signature induction. Mass cytometry-based immunophenotyping was utilized to characterize changes in immune cell prevalence and activation status of cryopreserved cells from both the PB and BM. Results: As of June 2020, 59 patients had been treated on all schedules. The median number of prior lines of therapy was 7 (range: 3-20); 93% had received at least 1 daratumumab-containing regimen, and 14% had received previous CAR-T cell therapy. Thrombocytopenia was the most frequent TEAE (83%) and was Grade ≥3 in 28 (47%) pts. Prolonged thrombocytopenia was a dose limiting toxicity (DLT) in 7 pts, but was not associated with clinical bleeding, and 9 pts required platelet transfusions. Neutropenia was reported as a TEAE in 54% of pts (Grade ≥3 in 49% pts), and was a DLT in 4 patients, including one pt who had febrile neutropenia. The maximum tolerated dose for the initial schedule was 0.1 mg/kg, and evaluation of other schedules is ongoing. Myeloma responses have been observed starting at doses of 0.1 mg/kg on the initial schedule, 0.4 mg/kg q2 weeks, and 1.5 mg/kg q4 weeks (as shown in Table 1). Single administration of TAK-573 resulted in a dose dependent increase in CD38 RO of PB-derived immune cells, with saturation of CD38 RO 4 hours after the end of infusion (EOI) at doses ≥ 0.2 mg/kg. The duration of saturation was dose dependent, with doses ≥ 0.75 mg/kg TAK-573 saturating CD38 RO through 24 hours. CD38 RO in BM samples showed similar results, with added variability due to the timing of sample collection and individual patients' tumor burden. At all dose levels, TAK-573 administration resulted in increases in the type I IFN gene signature 24 hours after the dose. As CD38 is an IFN-stimulated gene, TAK-573 treatment resulted in CD38 RD increases, most notably on NK cells but also on other CD38 positive cells, including MM cells within the BM. BM MM cells also showed decreases in complement-inhibitory proteins CD55 and CD59 after TAK-573 treatment. Circulating levels of IFN-associated chemokines (IFNγ, CXCL10, MCP-1 and IL-15) also increased, with maximal induction 4 hours after EOI. CD69 expression, a marker of early activation, increased on BM CD8+ T cells in 7 of 9 patients analyzed; the CD8+ T-cells for 3 of those 7 patients also showed increases in IFNγ positivity, indicating that TAK-573 treatment can increase the cytolytic potential of CD8+ T-cells in the BM of a subset of patients. Conclusion: TAK-573 is a clinically and pharmacologically active molecule that mediates IFNAR pathway modulation and leads to myeloma responses. Additional biomarker data is being collected to further refine the MOA, which will inform the recommended phase 2 dose, optimal schedule of administration, and rational development of TAK-573. Disclosures Vogl: Active Biotech: Consultancy, Research Funding; Takeda: Consultancy; Karyopharm: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Oncopeptides: Consultancy; MorphoSys: Consultancy. Kaufman:Takeda: Consultancy, Honoraria; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Sanofi/Genyzme: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Tecnopharma: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; AbbVie: Consultancy. Holstein:GSK: Consultancy; Celgene: Consultancy; Sorrento: Consultancy; Sanofi: Consultancy; Oncopeptides: Consultancy, Research Funding; Takeda: Consultancy; Adaptive Biotechnologies: Consultancy; Genentech: Consultancy. Nadeem:Takeda: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees. Suryanarayan:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Current Employment. Collins:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Current Employment. Parot:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Current Employment. Chaudhry:Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: TAK-573 is a first-in-class, humanized, anti-CD38, IgG4 monoclonal antibody genetically fused to 2 attenuated interferon alpha-2b (IFNα2b) molecules

Introduction MM is a clonal disorder of malignant plasma cells. Standard of care for newly diagnosed MM is induction with triplet regimen chemotherapy followed by ASCT. Patients are stratified based on cytogenetic analysis as being high risk and standard risk. t(11;14) comprises ∼ 15-20% of newly diagnosed MM, making it the most common translocation. t(11;14) has been classified as standard risk. However, it is now increasingly being considered as intermediate risk, conferring inferior outcome compared with standard-risk MM.(Walker, Wardell et al. 2012) Methods We performed a retrospective analysis of 806 pts with newly diagnosed MM who underwent ASCT at our institution. Pts were stratified as high risk in the presence of t(4;14), t(14;16), gain 1q or del17p.by FISH. PFS and OS rates were estimated using Kaplan-Meier method. Log-rank tests were used to compare the PFS and OS between the two groups. The Cox proportional hazard models were used to estimate the hazard ratios (HR). Results Among 806 patients, 156 pts (19.4%) were positive for t(11;14). 81.5% of pts were 65 yrs or younger, and 59% were males. There were no significant differences in pt characteristics (see table) Median PFS from ASCT in pts with t(11;14) was 3.0 yrs (95% CI: 2.3-4.3) vs. 3.3 yrs (95% CI: 2.8-3.8) in those without t(11;14)[HR=1.03, 95% CI: 0.82-1.29, p=0.81. There was no statistical difference in OS from ASCT [HR of 0.97 (95% CI: 0.70-1.33, p 0.84)]. 5 yr PFS rate was 37% for pts with t(11;14) & 53% in pts without. 5 yr OS rate was 65% for pts with t(11;14) & 66% for those without. Conclusion t(11;14) is a common cytogenetic abnormality in MM. According to our analysis, there is no significant difference in outcomes following ASCT in both high risk and standard risk subgroups. t(11;14) MM is predicted to be BCL-2 dependent and the use of BCL-2 inhibitors in induction or post-ASCT maintenance is an attractive option to improve outcomes.

Introduction Multiple myeloma (MM) represents 1.8% of all new cancer cases in the U.S. While not curable, advances in treatment, including autologous stem cell transplant (ASCT) and maintenance therapy, have dramatically improved progression free survival (PFS) and overall survival (OS). The Ohio State University began utilizing ASCT for newly diagnosed MM (NDMM) patients in 1992. With the introduction of new, more effective drugs used before and after ASCT over time, we performed retrospective survival analysis in NDMM patients receiving ASCT from 1992-2016. Method Consecutive 1002 NDMM patients were eligible. Patients were split into five groups based on historic changes in novel agents for treatment of MM: 1992-1998-group 1, 1999-2002-group 2, 2003-2008-group 3, 2009-2013-group 4, and 2014-2016-group 5. Pre-ASCT conditioning regimen was melphalan, 140 or 200 mg/m2. High-risk patients had del17, t(4:14), t(14:16), and/or 1q abnormality. Primary endpoints were PFS and OS. Kaplan Meier curves were used to calculate PFS and OS. Results Across the years (1992-2016), there was a statistically significant improvement in both PFS (p 65 years old, there was a statistically significant improvement in PFS (p Conclusion Survival since 1992 have improved primarily due to inclusion of novel therapies and maintenance. For NDMM patients receiving ASCT, the 3 year overall survival rate has significantly improved from 45% in 1992-1998 to 80% in 2014-2016, which is similar to the post-ASCT OS shown in the 2012 study by McCarthy et al. The significantly increasing age of NDMM patients receiving ASCT over time suggests improvement in supportive care and tolerability of current therapies.

Introduction Autologous stem cell transplantation (ASCT) remains an effective treatment option for many patients with systemic AL amyloidosis (AL). However, the decision to utilize maintenance therapy following ASCT remains controversial and largely unexplored. Furthermore, the growing relevance of cytogenetics in AL may help dictate this maintenance decision as well. It is also relevant to note the emergence of novel targeted therapy options for AL patients, including the plasma cell monoclonal antibody daratumumab, that offer an exciting option in combination therapies with ASCT. As such, the present study aims to a) determine the prognostic significance of utilizing maintenance therapy following ASCT b) assess the potential impact of cytogenetics on this decision, and c) present novel data on the survival benefits of daratumumab-treated patients who have undergone ASCT. Methods A retrospective chart review was performed on 50 consecutive AL patients who underwent ASCT at The Ohio State University. Patients received high dose Melphalan (140 or 200 mg/m2) prior to ASCT. Patients were divided into subgroups based on FISH, and whether or not they had received maintenance therapy following transplant. Primary endpoints were progression free survival (PFS) and overall survival (OS), both estimated via the Kaplan-Meier survival function. The log-rank test was used to test the equality of survivor functions between different groups of patients. Results Twenty-eight patients (56%) received maintenance and 22 (44%) did not. There was no difference in age, dose of melphalan used, disease stage and number of organs involved between the two groups. There was no statistically significant difference in OS (p=0.32) and PFS (p=0.66) between patients who received maintenance versus those patients who did not receive maintenance (Figure 1A). Among patients with abnormal FISH, there was no difference in survival between the two groups (OS-p=0.65; PFS-p=0.15) (Figure 1B). Patients with three or more organs with AL involvement had worse OS/PFS versus those with 2 or less (OS-p=0.001; PFS-p=0.015). However, among these patients with 2 or more organs involved, the decision to utilize maintenance vs not showed no difference in PFS/OS. Lastly, further evaluation of a subset of patients treated with daratumumab showed no difference in outcome whether or not they underwent ASCT or consolidation. Conclusion In this small retrospective analysis, maintenance therapy post ASCT had no impact on the PFS or OS of patients with AL, even when further stratified based on degree of organ involvement. Survival was also not affected by cytogenetic abnormalities or with addition of novel monoclonal-targeted therapies. It is clear that a larger prospective study is needed to assess the benefit of maintenance post ASCT in AL amyloid patients.

Introduction: Despite rapid advances in myeloma treatment with the development of new drugs, curative therapies remain elusive. Relapsed/refractory disease related to progressive dysregulation of immune system and acquired genetic abnormalities continues to be a major obstacle in achieving cure. Immune-based therapy harnessing the host defense mechanism of natural killer (NK) cells is a promising avenue in the treatment of myeloma. Areas covered: Here, we discuss the biology and cytotoxic activity of NK cells and the potential role of these innate immune cells in defense against cancer and specifically multiple myeloma. We also discuss the role of NK cells in the anti-myeloma effects of autologous and allogeneic stem cell transplantation, various novel drugs, and treatment modalities such as chimeric antigen receptor therapy. Immune evasion, either directly or indirectly involving NK cell dysfunction, may be a key and under-recognized mechanism in myeloma progression. We reviewed extensive literature identified using the keywords immunotherapy, natural killer cells, and multiple myeloma. Expert opinion: Novel treatment approaches in myeloma utilizing the immunomodulatory and cytotoxic properties of NK cells to eradicate resistant and quiescent clones could pave the way for potentially curative interventions.

e20019 Background: Multiple myeloma (MM) is a malignancy that affects Black Americans (BA) more often and at earlier age than White Americans (WA). BAs still frequently receive suboptimal care and are underrepresented in clinical trials or retrospective analyses. However, recent studies have shown that BA MM patients treated with standard-of-care regimens have similar if not superior outcomes than WA patients. The median age of MM diagnosis is 69 years; but ten percent of individuals develop MM before age of 50 years. Limited data are available regarding the outcomes and characteristics of this younger patient population. Herein, we specifically investigate the outcome of young MM patients. Methods: We retrospectively analyzed young MM patients (age < 50) diagnosed between 1992 and 2016 at The Ohio State University Comprehensive Cancer Center. After informed consent, data pertaining to patient demographics and MM characteristics were collected in a coded database. Descriptive statistics was used to summarize disease characteristics; chi-square or Wilcoxon rank-sum tests were used to compare outcomes between BA and WA patients. Overall Survival (OS) was estimated by Kaplan-Meier method, with log-rank test applied to test the statistical differences between survival curves. Two-sided p-values

The novel clinical data for plasma cell neoplasms (smoldering myeloma, multiple myeloma, and AL amyloidosis) that were presented in the 2020 American Society of Clinical Oncology virtual scientific symposium are summarized here. Data from large phase-3 studies (CASSIOPEIA, ENDURANCE, and TOURMALINE-MM4 trials) and phase-2 studies (SWOG 1211, GMMG CONCEPT trials) for newly diagnosed multiple myeloma patients who are eligible for autologous stem cell transplantation are described. Updates from previous important studies for multiple myeloma (STaMINA) along with studies on three different chimeric antigen receptor (CAR-) T cell products are also described. Results of clinical studies involving the use of anti-myeloma drugs with novel mechanisms of action such as immunoconjugates, selinexor, venetoclax, monoclonal antibodies, and data on minimal residual disease (MRD) are discussed. These data provide an overview of the efficacy and safety of the various treatments in multiple myeloma and could lead to changes in our clinical practice, which could pave the path for a “cure” in myeloma.

Introduction: High-dose melphalan is the standard conditioning chemotherapy for autologous stem cell transplantation (ASCT) in multiple myeloma (MM). However, patients experience several side effects and toxicities from high-dose melphalan. In 2016, United States Food and Drug Administration approved Evomela, a propylene glycol-free formulation of melphalan, as conditioning chemotherapy for ASCT in MM. This was based on its bioequivalence to the standard propylene-glycol solubilized melphalan formulation (Alkeran) in a phase 2 study. Evomela has the advantages of improved solubility, stability, bioavailability and being free of propylene glycol that is associated with organ dysfunction. Methods: We conducted a retrospective study of patients who received ASCT with high dose chemotherapy using alkeran (n=255) or evomela (n=259) at our institution to compare their outcomes such as side effects, duration of cytopenias, transfusion requirements, length of hospital stay, readmission within 30 days and progression-free survival (PFS) post-SCT. Clinical and demographic characteristics were compared between two treatment regimens using the Chi-square test for categorical variables and the Wilcoxon rank sum test for the continuous variables. Overall survival (OS) was calculated from the date of transplant to death, censoring the alive patients at their last follow up date. Progression-free survival (PFS) was calculated from the date of transplant to date of relapse or death, whichever occurred first, censoring at the last follow-up if no relapse or death. OS and PFS estimates were calculated using the Kaplan-Meier method and compared using the log-rank test. Results: The baseline patient characteristics such as age, ISS stage, comorbidity index and number of prior lines of therapy prior to ASCT were similar between the two groups. (See table 1). Mucositis was seen in 77.2% of the patients who received Alkeran compared to 69.5% who received Evomela (p= Conclusion: We conclude that use of Evomela is associated with a better side-effect profile and transfusion requirement while having similar outcomes as Alkeran. Disclosures Yucebay: Janssen: Membership on an entity's Board of Directors or advisory committees; BioXCell: Membership on an entity's Board of Directors or advisory committees; G1 Therapeutics: Membership on an entity's Board of Directors or advisory committees. Chaudhry:Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees. Efebera:Takeda: Honoraria, Speakers Bureau; Pharmacyclics: Research Funding; Celgene: Research Funding; Ohio State University: Current Employment. Bumma:Amgen: Speakers Bureau; Sanofi: Speakers Bureau. Khan:Amgen: Consultancy; Janssen: Consultancy. Devarakonda:Janssen: Consultancy.

Introduction: Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a potentially curative treatment for many hematological malignancies and disorders. However, this potential is often impeded by several factors including relapse of the underlying disease, graft-vs-host disease (GVHD) and infectious complications. Specifically, acute GVHD continues to be a major factor in the morbidity and mortality of patients. Hence, the practice of allo-SCT is continuously evolving to mitigate these factors. In particular, advances in the conditioning regimens, GVHD prophylaxis, infectious disease monitoring and prophylaxis and supportive care not only have resulted in improved outcomes, but also have expanded potential indications for allo-HSCT. Therefore, we conducted a retrospective analysis on patients who underwent allo-SCT at The Ohio State University from 1986-2018 to better understand how survival has changed longitudinally in accordance with these therapeutic advancements. Method: We analyzed data from 1943 consecutive patients who received an allo-SCT. Patients were divided into seven groups based on the year of transplant: groups (gp) 1: 1984-1988, 2: 1989-1993, 3: 1994-1998, 4: 1999-2003, 5: 2004-2008, 6: 2009-2013, and 7: 2014-2018. The primary endpoints were overall survival (OS) and progression free survival (PFS), and log-rank test was used to compare across transplant years. The Kaplan-Meier method was used to estimate OS and PFS. The secondary endpoints were the cumulative incidences of grade II-IV and grade III-IV acute GVHD (aGVHD), chronic GVHD (cGVHD), and non-relapse mortality (NRM). Cumulative incidence rates were estimated and compared using Gray's test accounting for competing risks. Results: Across the years (1984-2018), the median age was 50.0 (range: 18-76) with 59.6% of the patients being male. Acute myeloid leukemia accounted for 36.3% of transplants, followed by non-Hodgkin lymphoma (14.2%), acute lymphoid leukemia (11.8%), chronic myeloid leukemia (10.1%), and myelodysplastic syndrome (10.0%). Fifty-five percent of patients received myeloablative conditioning. Across the groups, statistically significant improvements in PFS and OS were observed (p Conclusion: Our data shows improved overall and progression-free survival post allo-SCT over decades, which may be attributed to advances in supportive care, and GVHD and relapse mitigation therapy. The decline in NRM is also likely due to improved supportive measures such as infectious disease monitoring and prophylaxis. Nonetheless, post-transplant relapse and grade III-IV aGVHD remain prominent challenges. Therefore, future research should continue to investigate therapeutic strategies that can both reduce high grade GVHD while limiting post-transplant relapse. Disclosures Chaudhry: Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees. Bumma:Amgen: Speakers Bureau; Sanofi: Speakers Bureau. Khan:Amgen: Consultancy; Janssen: Consultancy. Devarakonda:Janssen: Consultancy. Vasu:Kiadis Inc: Other: Kiadis has obtained exclusive licensing requirements from The OHio State University; Janssen: Membership on an entity's Board of Directors or advisory committees; Omeros: Membership on an entity's Board of Directors or advisory committees. Jaglowski:CRISPR: Consultancy; Novartis: Consultancy, Research Funding; Juno: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding. William:Incyte: Research Funding; Guidepoint Global: Consultancy; Dova: Research Funding; Merck: Research Funding; Seattle Genetics: Research Funding; Kyowa Kirin: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Mims:Leukemia and Lymphoma Society: Other: Senior Medical Director for Beat AML Study; Agios: Consultancy; Abbvie: Membership on an entity's Board of Directors or advisory committees; Syndax Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Other: Data Safety Monitoring Board; Kura Oncology: Membership on an entity's Board of Directors or advisory committees; Novartis: Speakers Bureau. Brammer:Bristol-Myers Squibb: Research Funding; Celgene: Research Funding; Seattle Genetics: Honoraria, Speakers Bureau; Kymera: Honoraria; Verastem Oncology: Other: Travel. Saad:Incyte Pharmaceuticals: Other: Personal Fees; Amgen: Other: research support; Kadmon: Other: research support; Orcabio: Other: research support; Magenta Therapeutics: Other: Personal Fees. Efebera:Celgene: Research Funding; Takeda: Honoraria, Speakers Bureau; Pharmacyclics: Research Funding; Ohio State University: Current Employment.

Introduction: Allogeneic stem cell transplant (allo-SCT) plays a key role in the post-remission therapy for acute myeloid leukemia (AML) patients due to its high rates of efficacy as compared to alternate therapies. For patients with relapsed/refractory AML and those with high-risk myelodysplastic syndrome (MDS), it remains the sole curative option. However, these patients continue to have significant obstacles for successful transplant including risk for relapse of underlying disease, graft versus host disease (GVHD), and infectious complications. Outcomes of allo-SCT in these patients have improved over time with the evolution of practice of allo-SCT, including modifications of transplant conditioning regimens, supportive care, and earlier recognition of transplant complications. Our study sought to assess the trends in survival in AML and MDS patients undergoing allogeneic transplant at The Ohio State University from 1984-2018. Methods: We analyzed data from 900 consecutive patients who received an allo-SCT (705 AML and 195 MDS). The patients were stratified into 7 different groups based on year of transplant using 5 year increments; group (gp) 1 included 1984-1988, gp 2 1989-1993, gp 3 1994-1998, gp 4 1999-2003, gp 5 2004-2008, gp 6 2009-2013, and gp 7 2014-2018. Progression free survival (PFS) and overall survival (OS) were utilized as primary end points. PFS and OS were calculated using Kaplan Meier Curves. Secondary endpoints included cumulative incidences of grade II-IV and III-IV acute GVHD (aGVHD), chronic GVHD (cGVHD), and non-relapse mortality (NRM). Cumulative incidence rates were estimated and compared using Gray's test accounting for competing risks. Results: Median age at transplant was 52 years (yrs) old (range 18-76) and 55.6% were male. Patients having myeloablative (MA) conditioning regimen comprised 57.6% of the cohort. From 1984 to 2018, there was a statistically significant improvement in both PFS and OS (Figure 1 a and b; p Conclusion: Our study demonstrates significant improvement over the past several decades in survival in AML and MDS patients undergoing allo-SCT. Major factors that likely contribute to improvement in outcomes throughout the years include adjustments in conditioning regimens and GVHD prophylaxis, earlier recognition of complications as well as improved management, and improved general supportive care. Overall, while outcomes have improved significantly throughout the years, post-transplant relapses remains the leading cause of transplant failure in this group. Preventing relapse post-transplant represents a continued target for research today. Disclosures Chaudhry: Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees. Bumma:Amgen: Speakers Bureau; Sanofi: Speakers Bureau. Khan:Amgen: Consultancy; Janssen: Consultancy. Devarakonda:Janssen: Consultancy. Vasu:Omeros: Membership on an entity's Board of Directors or advisory committees; 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. Jaglowski:CRISPR: Consultancy; Novartis: Consultancy, Research Funding; Juno: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding. William:Kyowa Kirin: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Guidepoint Global: Consultancy; Incyte: Research Funding; Seattle Genetics: Research Funding; Merck: Research Funding; Dova: Research Funding. Mims:Novartis: Speakers Bureau; Agios: Consultancy; Leukemia and Lymphoma Society: Other: Senior Medical Director for Beat AML Study; Abbvie: Membership on an entity's Board of Directors or advisory committees; Kura Oncology: Membership on an entity's Board of Directors or advisory committees; Syndax Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Other: Data Safety Monitoring Board. Brammer:Seattle Genetics, Inc.: Speakers Bureau; Celgene Corporation: Research Funding. Efebera:Celgene: Research Funding; Pharmacyclics: Research Funding; Takeda: Honoraria, Speakers Bureau; Ohio State University: Current Employment.

Introduction-Chronic graft-versus-host disease (cGVHD) poses as a major late complication of hematopoietic stem cell transplantation. The role of cGVHD as a determinant in transplant-related morbidity and mortality, infectious complications, prolonged immune suppression, and impaired patient-reported quality of life has been extensively studied. Nonetheless, numerous advances in allogeneic hematopoietic stem cell transplant (allo-SCT) in recent years have expanded the indications for allo-SCT to a broader range of patients, including previously excluded older patients. However, long-term health status of older transplant recipients is poorly studied. Notably, the incidence of cGVHD may increase with age. Therefore, the development of cGVHD and the use of immunosuppressive therapy may lead to a higher degree of non-relapse mortality (NRM) in older patients. The objective of this study was to compare the NRM in both younger and older transplant recipients with and without cGVHD. Methods-We performed a retrospective cohort study of patients that underwent allo-SCT at the Ohio State University from 1999 to 2018. Data was analyzed from 1194 patients who survived or have been followed up with by at least day (d) 180 post-transplantation, among which 373 patients had developed cGVHD. Patients were grouped based on their age into a younger and older population. The older population was defined as ≥60 (N=373, 31%) with the younger population defined as Results-The median age at allo-SCT was 53.0 yr (range: 18-76) and 61.1% were male. Acute myeloid leukemia accounted for 36.7% of transplants, followed by non-Hodgkin's lymphoma (14.8%), acute lymphoid leukemia (12.7%), and myelodysplastic syndrome (11.0%). Additionally, 58.0% received reduced-intensity conditioning regimen. The majority of stem cell donor types were match unrelated (45.3%) and match related (39.8%). Patients who had developed cGVHD by d180, regardless of age, were at higher risk of NRM compared to patients with no cGVHD (hazard ratio [HR]: 1.52, 95% confidence interval [CI]: 1.16-1.99; p=0.002). To examine the influence of age with NRM, we stratified the analysis by cGVHD status by d180. Among patients developed cGVHD by d180, in both univariable (HR 1.22, 95% CI 0.79-1.9, p=0.373) and multivariable analysis (HR: 1.17, 95% CI: 0.74-1.87; p=0.501), there was no statistically significant difference in NRM between patients ≥60 and Conclusion-This study showed that patients with cGVHD by day 180 were at higher risk for higher NRM compared to patients without cGVHD. Among cGVHD patients, there was no difference on the outcome of older patients (≥60 years old) compared to younger ones ( Disclosures Chaudhry: Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees. Bumma:Sanofi: Speakers Bureau; Amgen: Speakers Bureau. Khan:Amgen: Consultancy; Janssen: Consultancy. Devarakonda:Janssen: Consultancy. Vasu:Kiadis Inc: Other: Kiadis has obtained exclusive licensing requirements from The OHio State University; Janssen: Membership on an entity's Board of Directors or advisory committees; Omeros: Membership on an entity's Board of Directors or advisory committees. Jaglowski:Novartis: Consultancy, Research Funding; Juno: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding; CRISPR: Consultancy. William:Celgene: Consultancy, Honoraria; Dova: Research Funding; Guidepoint Global: Consultancy; Merck: Research Funding; Kyowa Kirin: Consultancy, Honoraria; Seattle Genetics: Research Funding; Incyte: Research Funding. Mims:Syndax Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Other: Data Safety Monitoring Board; Abbvie: Membership on an entity's Board of Directors or advisory committees; Kura Oncology: Membership on an entity's Board of Directors or advisory committees; Leukemia and Lymphoma Society: Other: Senior Medical Director for Beat AML Study; Novartis: Speakers Bureau; Agios: Consultancy. Brammer:Bristol-Myers Squibb: Research Funding; Celgene: Research Funding; Seattle Genetics: Honoraria, Speakers Bureau; Kymera: Honoraria; Verastem Oncology: Other: Travel. Saad:Magenta Therapeutics: Other: Personal Fees; Incyte Pharmaceuticals: Other: Personal Fees; Amgen: Other: research support; Kadmon: Other: research support; Orcabio: Other: research support. Efebera:Takeda: Honoraria, Speakers Bureau; Pharmacyclics: Research Funding; Celgene: Research Funding; Ohio State University: Current Employment.

e20534 Background: Daratumumab, a monoclonal antibody against CD38, is very effective in patients with Multiple Myeloma (MM). CD38 is expressed on MM cells but also on normal lymphocytes. Therapy-induced lymphopenia has been reported in 30-40% of patients; however its clinical significance is vastly unexplored. Methods: Here, we report the baseline characteristics and clinical course of 100 relapsed/refractory MM patients treated at the Ohio State University with Daratumumab as single agent or in combination. Data pertaining to patient demographics, MM characteristics, absolute lymphocyte count-ALC, infections, and hospital stays were collected. ALC of less or equal to 500 cells/µL is considered severe lymphopenia. Results: Fifty-nine percent of patients who completed treatment with Daratumumab (59%) developed severe lymphopenia. MM type (LLC and IgA), combination with immunomodulatory drugs (IMIDs), and lower baseline ALC count were statistically associated with severe lymphopenia, while stage, age, cytogenetics, number of prior lines of treatment, and autologous stem cell transplant were not. Patients with severe lymphopenia had higher rates of infections (52.5% versus 41.4%) and required hospital stays more frequently (83.8% versus 52.9%) than patients without severe lymphopenia. Upper respiratory tract infections and pneumonias were the most common infections. Sixty-one percent of severely lymphopenic patients recovered to ALC > 500 lymphocyte/μL while on therapy. The median time to recover was 14 days (average 43 days). Older patients have longer ALC recovery time (average: 52 days versus 24 days). No statistically significant difference in progression-free survival (PFS), overall survival (OS), or overall response rate (ORR) was noted between patients who did or did not develop severe lymphopenia. However, when the severe lymphopenic group was stratified based on ALC recovery, those with persistent lymphopenia had worst OS (p = 0.0019) and PFS (p < 0.0001), possibly due to better immune-mediated anti-tumoral effects. Conclusions: In our patient population, we discovered an elevated rate of severe lymphopenia, hospital utilization, and infections. Persistent severe lymphopenia is associated with shorter PFS and worst OS. Combination with IMIDs and low baseline ALC count are risk factors for severe lymphopenia while patients older than 65 has a longer ALC recovery time. These findings underline the importance of monitoring lymphocyte count and considering prophylactic measures in high-risk patients treated with Daratumumab.

Introduction High dose chemotherapy followed by ASCT is the standard of care in the treatment of eligible patients with MM. Melphalan has been the drug of choice for conditioning therapy at a dose of 200 mg/m2 (mel 200). However, for elderly patients (older than 65 years) and renal dysfunction (serum creatinine>2), a reduced dose of 140 mg/m2 (mel 140) is commonly used based on a prior retrospective study. We conducted a retrospective analysis comparing the outcomes of patients with MM who underwent ASCT at our institution at the standard dose of melphalan versus reduced dose. Objectives 1) Compare efficacy of melphalan 200mg/m2 versus 140mg/m2 for ASCT in MM. 2) Assess impact of age and renal dysfunction on the outcome in MM. 3) Compare the clinical characteristics of patients who underwent ASCT. Methods We performed a retrospective analysis of 1002 consecutive patients with newly diagnosed MM who underwent ASCT at The Ohio State University between 1992 through 2016. Data were collected regarding patient demographics, disease characteristics, therapy received, dose of melphalan conditioning and clinical outcomes. Progression-free survival (PFS) was defined from time of transplantation to disease progression or death, censoring those alive without progression at the last contact. Overall survival (OS) was calculated from the time of transplantation to death, censoring those alive at last contact. PFS and OS were estimated using Kaplan-Meier method. Log-rank tests were used to compare PFS and OS between the groups, and Cox proportional hazard models were used to estimate the hazard ratios (HR). Results 946 patients received high dose melphalan conditioning prior to ASCT, of which 807 patients received mel 200 while 126 patients received mel 140. Thirteen patients were excluded due to alternate dosing. Around 16% of patients in the mel 200 group were older than 65 years compared to 42.1% in the mel 140 group. More patients in the mel 140 group had ISS stage 3 MM compared to mel 200 (64.7% vs 24.6%). Renal dysfunction was seen in 69.8% of patients in the mel 140 group while 15.5% had it in the mel 200 group. PFS of patients who received mel 140 was not inferior to those who received mel 200 (p=0.29, figure 1). Overall survival of patients who received mel 200 was better than those who got mel 140 by univariate analysis (p=0.048, figure 1). However, after adjusting for age, ISS staging and renal dysfunction, the difference in OS was not significant. Conclusion Patients who got mel 140 did no worse than those who received mel 200 in terms of disease outcome as assessed by PFS and OS.

Introduction Acute graft versus host disease (aGVHD) remains a leading cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HSCT). Preventing GVHD without impairing the graft-versus-tumor effect remains an important goal for successful allo-HSCT. Tacrolimus (TAC), a calcineurin inhibitor that prevents T-cell activation, is commonly used as aGVHD prophylaxis. The influence of TAC has proved effective for preventing aGVHD after allo-HSCT. There is also variability in the serum concentrations of TAC and very little is known on the impact of early (first 4 weeks) TAC levels on aGVHD incidence. Methods Data were analyzed for 707 consecutive patients undergoing allo-HSCT at the Ohio State University between 2002- 2016. All patients received standard prophylaxis with TAC daily and methotrexate on days +1, +3, +6, and +11 post allo-HSCT. Tacrolimus dose was adjusted to achieve a target serum level of 5-12 ng/ml. Fine and Gray's proportional hazard models accounting for competing risks were used to evaluate the association between TAC levels and outcome of aGVHD, cGVHD, GVHD-free/relapse-free survival (GRFS),and relapse. Cox proportional hazard models were used for the association with OS. Results The mean weekly TAC concentrations at weeks 1, 2, 3 and 4 were 8.0, 9.7, 11.3 and 10.5 ng/mL, respectively. The cumulative incidence of grades II–IV aGVHD was 40% at day 100 and 45% at day 180 post HSCT. In univariable analysis, high TAC level at week 1 was associated with lower grade II-IV aGVHD (Hazard ratio (HR), 0.96; p = 0.006). We examined the effect of week 1 TAC levels categorized into tertiles ( 8.95 ng/ml). Higher level of TAC (>8.95 ng/ml) was associated with lower risk of aGVHD (Figure 1a). In multivariable analysis, week 1 TAC levels > 5.85 ng/ml remained associated with a lower risk of grade II-IV aGVHD. However, only levels of 5.85-8.95 ng/ml were associated with statistically significant lower risk with HR=0.75, p=0.04 compared to the lower group ( 7.2 ng/ml (HR: 0.78, p=0.03). The CI of cGVHD was 41% at 1 year post-allo-HSCT. Week 2 TAC level >10.6 ng/ml was associated with an increased risk of relapse (HR, 1.37, p=0.043) (Figure 1b). The cumulative incidence of relapse at 1, 3 and 5 year post allo-HSCT was 33%, 38% and 40%, respectively. TAC levels at weeks 1, 2, 3 and 4 were not associated with OS. The 1, 3 and 5 year GRFS was 21%, 14% and 12%.TAC levels at any week were not associated with GRFS. Conclusion Achieving mean whole-blood level of tacrolimus between 6.0-9.0 ng/ml within the first week post-allogenic bone marrow transplantation may reduce the risk of aGVHD.

Introduction A meta-analysis of three large randomized trials has demonstrated that len maint prolongs progression free survival (PFS) and overall survival (OS) in pts with MM who have undergone ASCT. While len maint benefits pts with both high-risk and standard-risk cytogenetics, it does not appear to provide equal magnitude of benefit to patients with high-risk cytogenetics. We conducted a retrospective analysis comparing the outcomes of pts with MM who underwent ASCT at our institution and len maint compared to no maint. We further evaluated the impact of len maint on the two cytogenetic groups. Methods We performed a retrospective analysis of 1002 consecutive pts with newly diagnosed MM who underwent ASCT at The Ohio State University between 1992 through 2016. Data were collected regarding patient demographics, disease characteristics, therapy received including maint, and clinical outcomes. Pts were excluded from the analysis if they received len combination or other drug maint therapies. High-risk cytogenetics was defined as having t(4;14), t(14;16), gain 1q, or del17p. PFS and OS were estimated using Kaplan-Meier method. Log-rank test was used to compare PFS and OS between the groups and Cox proportional hazard models were used to estimate the hazard ratios (HR). Results Pt characteristics are listed in Table 1. 484 pts (53.3%) received no maint while 423 pts (46.7%) received len maint. 245 pts (24.4%) had high-risk cytogenetics while 561 pts (56%) had standard-risk cytogenetics with the remaining unknown. Both PFS and OS were significantly better in the len maint group compared to the no maint group (Figure 1). Adjusting for pts age at transplant, cytogenetic risk, pre-transplant and post-transplant disease status, and ISS staging, the superiority in PFS and OS remained statistically significant, HR=0.50 (95% CI: 0.41-0.62), p Conclusion Consistent with previously published data, our results demonstrate an improvement in outcomes in MM pts treated with len maint following ASCT compared to no maint regardless of cytogenetic risk group. Larger studies are needed to assess the individual benefit obtained with len maint with each high-risk cytogenetic abnormality. Several trials incorporating newer drugs with novel mechanisms of action are currently being done that could further optimize maint therapy and lead to better outcomes in high-risk group.

Chronic lymphocytic leukemia/small lymphocytic lymphoma is the most prevalent form of adult leukemia in western countries. Chemotherapy has been the mainstay of treatment for the last several decades. The introduction of biological, targeted agents (e.g., monoclonal antibodies) has dramatically improved treatment options. The addition of rituximab to fludarabine and cyclophosphamide has improved patient outcomes, as compared to fludarabine and cyclophosphamide. Nevertheless, chronic lymphocytic leukemia remains incurable, leaving considerable room for improvement. One approach would be to enhance the activity of the CD20 antibody. The next-generation monoclonal antibody ofatumumab has not demonstrated superiority over rituximab, whereas obinutuzumab-chlorambucil is superior to rituximab-chlorambucil. Recent efforts to combine anti-CD20 antibodies with new targeted therapies offer the potential to move toward alternative non-chemotherapy-based treatment approaches.

Background: Daratumumab, a human monoclonal antibody that binds CD38, has been recently approved to treat patients with Multiple Myeloma (MM), a disease of clonal plasma cells. Daratumumab is generally well-tolerated; however, lymphopenia and neutropenia can occur while on treatment. Hereby, we report real-world experience of rates, trends, and outcomes of patients who developed lymphopenia while being treated with Daratumumab in our institution. Methods: Patients who received Daratumumab between November 2015 and July 2019 at the Ohio State University in Columbus, Ohio were identified, retrospectively. Data pertaining to patient demographics, prior lines of therapy, MM staging, absolute lymphocyte count (at start, nadir, and end of treatment), infections, ED visits, and hospital stays were collected. Absolute Lymphocyte count (ALC) of less or equal to 500 cells/μL was considered severe lymphopenia. Results: One hundred patients who completed Daratumumab treatment in our institution between November 2015 and July 2019 were included. Fifty-nine patients (59%) developed severe lymphopenia with an absolute lymphocyte count (ALC) nadir equal to or less than 500 lymphocytes/μL. Sixty-one percent of them (36/59) recovered on therapy to ALC >500 lymphocyte/μL with 16 of them recovering to normal ALC (>1000 lymphocyte/μL). The median time to become severely lymphopenic was 31 days, with an average of 64 days (range 0-453). The median time to recover was 14 days (average 43 days; range 1-453). Patients with severe lymphopenia had a higher rate of infections (52.5%) compared to patients without lymphopenia (41.4%). Among the patients who had infections, patients with severe lymphopenia required hospital stays in 83.8% of the cases compared to 52.9% of the cases for the patients without severe lymphopenia (p-value= 0.03, Odd Ratio-OR: 4.6; 95% CI, 1.186 to 17.70). The most common infections were viral upper respiratory tract infections and pneumonias (22/31-71%). However, more serious infections, such as CMV/EBV reactivation, influenza A/B infection, fungal meningitis, and bacteremia occurred in our patient population. No statistically significant difference in terms of progression-free survival (PFS), overall survival (OS), or overall response rate (ORR) (58.5% versus 50.8%) was noted between patients who did or did not develop severe lymphopenia. However, when the severe lymphopenic group was stratified based on the presence of recovery, those who did not recover their ALC had worst OS (p= 0.0019) and PFS (p Average age (64.9 vs 66.1), number of prior lines of treatment (4.1 vs 3.8) or prior transplant (72.8% vs 65.8%) were not associated with development of severe lymphopenia. Patients older than 65 had similar ALC nadir values (median 425, range 0-2250 vs median 400, range 0-1940), rates of lymphopenia (55.7% vs 62.5%, OR, 1.322; 95% CI, 0.5774 to 2.845) and time to severe lymphopenia (75.3, range 7-453 vs 58.88, range 0-254) than younger patients. However, they tended to recover slower than younger patients (average: 52 days vs 24 days). Only 26 of our patients received Daratumumab as single agent, while fifty-five of them were treated in combination with immunomodulatory drugs (IMIDs- lenalidomide or pomalidomide) and sixteen in combination with proteasome inhibitors (PIs). When patients were divided by combination strategy, no statistical difference was noted in ALC nadir values; however, IMID combination caused severe lymphopenia in 38/55 patients (69%) compared to 11/26 patients (42.3%) treated with single agent regimen (p= 0.05, OR: 2.8). Patients treated with Bortezomib combination had a slower time to severe lymphopenia (p= 0.05 and p=0.01, respectively) but longer recovery time (p= 0.0081) than patients treated with single agent or IMIDs. Conclusions: In our patient population, we discovered an elevated rate of severe lymphopenia, hospital utilization and infections. IMID combination was associated with increased rates of lymphopenia, while PI-combination caused more prolonged lymphopenia. Age more than 65 was associated with longer ALC recovery time. Interestingly, patients who did not recover their ALC had worst OS and PFS compared to patients who never became severly lymphopenic or patients who recovered their ALC count. Disclosures Efebera: Takeda: Honoraria; Janssen: Speakers Bureau; Akcea: Other: Advisory board, Speakers Bureau. Rosko:Vyxeos: Other: Travel support.

Introduction: Acute graft versus host disease (aGVHD) remains a leading cause of morbidity and mortality in allogeneic hematopoietic stem marrow transplant (allo-HSCT), with rates ranging from 30% to 70%. Preventing GVHD without impairing the graft-versus-tumor effect remains an important goal for successful allo-HSCT. Tacrolimus (TAC), a calcineurin inhibitor that prevents T-cell activation, is commonly used as aGVHD prophylaxis. The influence of TAC has proved effective for preventing aGVHD after allo-HSCT. There is also variability in the serum concentrations of TAC and very little is known on the impact of early (first 4 weeks) TAC levels on aGVHD incidence. Given the immunologic events that lead to aGVHD, which occur within the first few days after transplant, we sought to assess whether early TAC levels were associated with aGVHD. Methods: Data were analyzed for 707 consecutive patients undergoing allo-HSCT at the Ohio State University between 2002- 2016. All patients received standard prophylaxis with TAC daily and methotrexate at a dose of 5mg/m2 on days +1, +3, +6, and +11 post allo-HSCT. Patients received anti-thymoglobulin (ATG) if receiving stem cells from an unrelated/mismatch related donor. The TAC target range was 5-12 ng/mL averaged over a 7-day period. The primary outcome of interest was the incidence of aGVHD and its association with the mean weekly TAC levels. Secondary endpoints included incidence of chronic GVHD (cGVHD), relapse and overall survival (OS). Fine and Gray's proportional hazard models accounting for competing risks were used to evaluate the association between TAC levels and outcome of aGVHD, cGVHD and relapse. Cox proportional hazard models were used for the association with OS. Mean weekly TAC levels were included in the analyses as continuous variables and then divided into tertiles. A multivariable model adjusted for confounding factors. Results: Among the 707 patients, median age was 53 years (range: 19-75) and 60.7% were male. In all, 68% patients received reduced-intensity conditioning and the remaining 32% received myeloablative conditioning. The median age of donors was 34 years (range: 18-81) with 74.7% male. Of the donors, 36.9% were match related and 55.9% match unrelated. Peripheral blood was the stem cell source for 90.2% of the patients. A total of 449 (63.5%) patients received ATG. The diagnosis included acute myeloid leukemia (36.3%), non-Hodgkin lymphoma (16.41%), myelodysplastic syndrome (11.7%), and acute lymphoblastic leukemia (11.88%). The mean weekly TAC concentrations at weeks 1, 2, 3 and 4 were 8.0, 9.7, 11.3 and 10.5 ng/mL, respectively. The cumulative incidence of grades II-IV aGVHD was 40% (95% confidence interval (95% CI): 36%-43%) at day 100 and 45% (95% CI: 41%-48%) at day 180 post-transplant. In univariable analysis, high TAC level at week 1 was associated with lower grade II-IV aGVHD (Hazard ratio (HR), 0.96; 95%CI, 0.93-0.99; p = 0.006). We examined the effect of week 1 TAC levels categorized into tertiles (< 5.85, 5.85-8.95 and >8.95 ng/ml). Higher level of TAC (>8.95 ng/ml) was associated with lower risk of aGVHD (Figure 1a). In multivariable analysis, week 1 TAC levels > 5.85 ng/ml remained associated with a lower risk of grade II-IV aGVHD. However, only levels of 5.85-8.95 ng/ml were associated with statistically significant lower risk with HR=0.75 95% CI, 0.57-0.98; p=0.04 compared to the lower group (7.2 ng/ml (HR: 0.78, 95%CI: 0.62-0.98; p=0.03). The cumulative incidence of cGVHD was 41% (95% CI: 37%-44%) at 1 year post-allo-HSCT. Since GVHD is closely intertwined with the graft-versus-tumor effect, we examined whether early TAC levels influenced the risk of disease relapse. TAC levels at week 1 were not associated with relapse. However, week 2 TAC level >10.6 ng/ml was associated with an increased risk of relapse in multivariable analysis (HR, 1.37, CI, 1.01-1.85, p=0.043) (Figure 1b), after adjusting for confounding variables. The cumulative incidence of relapse at 1, 3 and 5 year post allo-HSCT was 33%, 38% and 40%, respectively. TAC levels at weeks 1, 2, 3 and 4 were not associated with OS. Conclusion: Achieving mean whole-blood level of tacrolimus between 6.0-9.0 ng/ml within the first week post-allogenic bone marrow transplantation may reduce the risk of aGVHD. Disclosures Rosko: Vyxeos: Other: Travel support. Vasu:Boehringer Ingelheim: Other: Travel support; Seattle Genetics: Other: Clinical trial support. Jaglowski:Kite: Consultancy, Other: advisory board, Research Funding; Juno: Consultancy, Other: advisory board; Novartis: Consultancy, Other: advisory board, Research Funding; Unum Therapeutics Inc.: Research Funding. William:Techspert: Consultancy; Guidepoint Global: Consultancy; Defined Health: Consultancy; Celgene Corporation: Consultancy; Kyowa Kirin, Inc.: Consultancy. Mims:Agios Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Astellas Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; PTC Therapeutics: Membership on an entity's Board of Directors or advisory committees. Brammer:Bioniz Therapeutics, Inc.: Research Funding; Viracta Therapeutics, Inc.: Research Funding; Verastem, Inc: Research Funding. Saad:Actinium Pharma Inc: Consultancy; Amgen: Other: Research Support; Kadmon: Other: Research Support; OrcaBio: Other: Research Support. Efebera:Janssen: Speakers Bureau; Akcea: Other: Advisory board, Speakers Bureau; Takeda: Honoraria.

Introduction-Multiple myeloma (MM) represents 1.8% of all new cancer cases in the U.S., with an estimated 32,110 new cases in 2019. While not curable, advances in treatment, including autologous stem cell transplant (ASCT) and maintenance therapy, have dramatically improved progression free survival (PFS) and overall survival (OS). The Ohio State University bone marrow transplant program began utilizing ASCT for newly diagnosed MM (NDMM) patients in 1992. With the introduction of new and more effective drugs used before and after ASCT, we performed survival analysis in NDMM patients from 1992-2016 receiving ASCT to examine our institutional progress. Method-We performed a retrospective analysis of 1002 consecutive transplant eligible NDMM patients. Patients were split into five groups based on historic changes in novel agents for treatment of MM: 1992-1998 (vincristine/doxorubicin/dexamethasone-group 1), 1999-2002 (thalidomide/dexamethasone-group 2), 2003-2008 (bortezomib/lenalidomide/dexamethasone-group 3), 2009-2013 (carfilzomib/pomalidomide/dexamethasone, and maintenance therapy-group 4), and 2014-2016 (agents used for relapsed MM, including daratumumab/elotuzumab/ixazomib/dexamethasone, and maintenance therapy-group 5). Pre-ASCT conditioning regimen was melphalan 140-200 mg/m2 in 94.4% of patients. Data were consistently obtained since 2003 for both standard and high-risk patients at diagnosis. High-risk patients had del17, t(4:14), t(14:16), hypodiploidy and/or 1q abnormality. Primary endpoints were PFS and OS. PFS was defined as time to progressive disease or death from any cause from the date of transplantation. OS was defined as time from transplantation to death from any cause, censoring those who were still alive at the last follow up. Kaplan Meier curves were used to calculate PFS and OS. Results-The median age of all patients at transplant was 58 years (range: 18-81 years) and 58.5% were male. The median patient age increased significantly, from 54 to 60 years, over 1992-2016 (p65 years old, there was a statistically significant improvement in PFS (p The rate of response both pre- and post-transplant showed statistically significant improvement across the years (p Conclusion-Our data show that NDMM patients' survival and response to standard of care treatment have improved dramatically since 1992, primarily due to inclusion of novel therapies and maintenance. For NDMM patients receiving ASCT, the 3 year overall survival rate has significantly improved from 45% in 1992-1998 to 80% in 2014-2016, which is similar to the post-ASCT OS shown in the 2012 study by McCarthy et al. The significantly increasing age of NDMM patients receiving ASCT over time suggests improving supportive care and expansion of standard of care therapies to more of the population, improving survival and quality of life. Disclosures Rosko: Vyxeos: Other: Travel support. Efebera:Takeda: Honoraria; Akcea: Other: Advisory board, Speakers Bureau; Janssen: Speakers Bureau.

Introduction: Autologous stem cell transplantation (ASCT) remains an effective treatment option for many patients with systemic AL amyloidosis (AL). However, the decision to utilize maintenance therapy following ASCT remains controversial and largely unexplored. Studies have shown the benefit of post-ASCT maintenance therapy in multiple myeloma (MM) with lenalidomide, but to date, no study has evaluated maintenance in AL patients following ASCT. Furthermore, the growing relevance of cytogenetics in AL may help dictate the incorporation of maintenance therapy as well. It is also relevant to note the emergence of novel targeted therapy options for AL patients, including the plasma cell monoclonal antibody daratumumab, that could be a valuable addition to combination therapies. As such, the present study aims to a) determine the prognostic significance of utilizing maintenance therapy following ASCT b) assess the potential role of cytogenetics on the efficacy of maintenance treatment, and c) investigate the outcomes of daratumumab-treated patients who have undergone ASCT. Methods: A retrospective chart review was performed on 50 consecutive AL patients treated at The Ohio State University who underwent ASCT. Patients received high dose Melphalan (140 or 200 mg/m2) prior to ASCT. Patients were divided into subgroups based on FISH data obtained within 90 days of diagnosis, as well as whether or not they had received maintenance therapy following transplant, which was defined as therapy greater than six months following ASCT. Patients' characteristics were summarized using medians and ranges, or frequencies and percentages, and compared using Mann-Whitney rank sum test or fisher exact test. Primary endpoints were progression free survival (PFS) and overall survival (OS), per updated NCCN guidelines, including both organ and hematologic criteria. PFS was defined as the time from date of transplant to day of progression or death from any cause. OS was defined as the time from date of transplant to death from any cause, with censoring those who were still alive at the last follow up. Kaplan-Meier survival function was used to estimate the PFS and OS. The log-rank test was used to test the equality of survivor functions between different groups of patients. Results: Twenty-eight patients (56%) received maintenance and 22 (44%) did not. Majority of patients received lenalidomide maintenance. The median age at transplant was 58 (range 33-71) years, with 66% male. There was no difference in age, dose of melphalan used, disease stage and number of organs involved between the two groups. There was no statistically significant difference in OS (p=0.32) and PFS (p=0.66) between patients who received maintenance versus those patients who did not receive maintenance (Figure 1A). Among patients with abnormal FISH, there was no difference in survival between these two groups as well (OS: p=0.65; PFS: p=0.15) (Figure 1B). Finally, we tested the efficacy of daratumumab in combination therapy with ASCT in a small patient subset. There was no difference in OS or PFS among patients who underwent ASCT for consolidation, whether or not they received daratumumab. Conclusion: In this small retrospective analysis, maintenance therapy post ASCT had no impact on the PFS or OS of patients with AL. Furthermore, survival was not affected by maintenance in patients with cytogenetic abnormalities or addition of novel monoclonal antibodies. A larger prospective study is needed to assess the benefit of maintenance post ASCT and daratumumab in AL amyloid patients. Disclosures Rosko: Vyxeos: Other: Travel support. Efebera:Janssen: Speakers Bureau; Akcea: Other: Advisory board, Speakers Bureau; Takeda: Honoraria.