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Background: Primary and secondary [post-essential thrombocythemia (ET) or polycythemia vera (PV)] Myelofibrosis (MF) are clonal hematopoietic neoplasms marked by constitutive JAK-STAT activation, bone marrow fibrosis, cytopenias, and constitutional symptom burden. Allogeneic hematopoietic cell transplantation (HCT) is the only curative option in this disease. Median overall survival (OS) after JAK inhibitor (JAKi) discontinuation is poor, ranging from 6-24 months (Harrision et al. Ann Hematol. 2020). Haploidentical (Haplo)-HCT with post-transplant cyclophosphamide (PTCy) has improved donor availability, but data on post-HCT outcomes in MF remain scarce. Herein, we describe clinical outcomes of patients (pts) with MF who underwent haplo-HCT with PTCy. Methods: We conducted a multi-institutional study where we retrospectively reviewed charts to obtain pt, disease, and treatment characteristics of MF pts who underwent haplo-HCT from 2000 to 2019. Graft-versus-host-disease (GVHD), relapse, and non-relapse mortality (NRM) were described as cumulative incidences. OS and relapse free survival (RFS) were estimated using the Kaplan-Meier method. Univariate analyses were conducted with Cox or Fine and Gray regression. Results: Fifty-eight adult pts from 11 centers underwent haplo-HCT and were included in the analysis. Pt, disease, and HCT characteristics are listed in Table 1. Thirty-four (59%) pts were over 60 years of age at the time of HCT. Of the 53 pts in whom driver mutation data was available, JAK2 was reported in 34 (64%), CALR in 10 (19%), MPL in 4 (8%), and 5 (9%) were triple-negative. Twenty-two (38%) pts had HCT-CI ≥ 3. Median CD34+ cell dose was 6.81 (range: 2.3-28.6) x 106/kg. All pts received PTCy as a part of GVHD prophylaxis regimen. Median follow-up in this study was 28 (range: 3.3-75.7) months. Neutrophil and platelet engraftment was reported in 53 (91%) and 47 (81%) pts at a median time of 20 (range: 14-70) and 31 (range: 15-225) days, respectively. Five pts (9%) had graft failure. The cumulative incidences of all-grade acute and chronic GVHD were in 44% (95% CI: 31-56%) at 6 months and 31% (95% CI: 18-44%) at 2 years. Grade 3-4 acute GVHD was seen in 5 (9%) pts. Post-HCT relapse/disease persistence occurred in 12 (21%) pts with a median of 416 (range: 28-917) days. The 2-year estimates of OS, RFS, relapse and NRM were 69% (95% CI: 55-80%), 52% (95% CI: 37-65%), 21% (95% CI: 11-34%) and 27% (95% CI: 16-39%) respectively (Fig 1). On univariate analyses (Table 2), older age (HR 2.17, P=.012) and a higher HCT-CI (HR 1.4, P<.001) was associated with higher NRM. Higher HCT-CI was also associated with higher all-cause mortality (HR 1.38, P=.003). Bone marrow as a graft source was associated with a higher risk of relapse (HR 5.04, P<0.001, Fig 2), but did not significantly affect OS (HR 0.78, 95% CI: 0.18-3.46), RFS (HR 1.89, 95% CI: 0.71-5.02) or NRM (HR 0.58, 95% CI: 0.09-3.84). JAKi use prior to HCT, spleen size or type of driver mutation did not significantly affect outcomes. Conclusions: Based on this study, we conclude that haplo-HCT with PTCy is a valid option in pts with MF. The graft failure rates appear to be similar to those reported with sibling and unrelated donors. Older age, higher HCT-CI and bone marrow as graft source were associated with inferior outcomes. JAKi use prior to HCT or type of driver mutation did not significantly affect outcomes. Disclosures Grunwald: Trovagene: Consultancy; Daiichi Sankyo: Consultancy; Merck: Consultancy; Agios: Consultancy; Janssen: Research Funding; Cardinal Health: Consultancy; Incyte: Consultancy, Research Funding; Daiichi Sankyo: Consultancy; Forma Therapeutics: Research Funding; Amgen: Consultancy; Celgene: Consultancy; Incyte: Consultancy, Research Funding; Celgene: Consultancy; Celgene: Consultancy; Pfizer: Consultancy; Incyte: Consultancy, Research Funding; Merck: Research Funding; Astellas: Consultancy; Genentech/Roche: Research Funding; Premier: Consultancy; Premier: Consultancy; Astellas: Consultancy; Premier: Consultancy; Daiichi Sankyo: Consultancy; Agios: Consultancy; Abbvie: Consultancy; Merck: Consultancy; Pfizer: Consultancy; Trovagene: Consultancy; Trovagene: Consultancy; Abbvie: Consultancy; Abbvie: Consultancy; Agios: Consultancy; Forma Therapeutics: Research Funding; Forma Therapeutics: Research Funding; Astellas: Consultancy; Amgen: Consultancy; Amgen: Consultancy; Merck: Consultancy; Cardinal Health: Consultancy; Pfizer: Consultancy; Cardinal Health: Consultancy; Janssen: Research Funding; Genentech/Roche: Research Funding; Genentech/Roche: Research Funding. Dholaria:J&J: Research Funding; Takeda: Research Funding; Angiocrine: Research Funding; bms: Research Funding; Poseida: Research Funding. Abedin:Jazz Pharmaceuticals: Honoraria; Agios: Honoraria; Helsinn Healthcare: Honoraria; Pfizer: Research Funding; Helsinn Healthcare: Research Funding; Actinium Pharmaceuticals: Research Funding. Gupta:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy; Incyte: Honoraria, Research Funding; Bristol MyersSquibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sierra Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees. DeZern:MEI: Consultancy; Celgene: Consultancy, Honoraria; Astex: Research Funding; Abbvie: Consultancy. Gerds:Sierra Oncology: Research Funding; Pfizer: Research Funding; Celgene: Consultancy, Research Funding; CTI Biopharma: Consultancy, Research Funding; AstraZeneca/MedImmune: Consultancy; Incyte Corporation: Consultancy, Research Funding; Apexx Oncology: Consultancy; Roche/Genentech: Research Funding; Imago Biosciences: Research Funding; Gilead Sciences: Research Funding. Jain:Bristol Myer Squibb: Other: for advisory board participation; Takeda: Consultancy, Honoraria; CareDx: Other: Advisory Board.

Introduction The molecular basis for the clinical heterogeneity observed in DLBCL was initially elucidated with gene expression profiling, identifying three distinct subgroups with prognostic relevance based on COO namely activated B-cell like (ABC), germinal center B-cell like (GCB) and a type 3 subtype. Shortly afterwards the Han's algorithm was developed allowing for widespread applicability and correlation of gene expression with protein expression. GCB profile at diagnosis is generally associated with superior long term outcomes compared to non-GCB in patients treated with conventional chemo-immunotherapy. Patients with relapsed/refractory disease (R/R) after front-line therapy undergo salvage treatment and, upon demonstration of objective response, proceed with high dose therapy and autologous transplantation (auto-HCT). Whether COO by Han's algorithm retains its prognostic significance post auto-HCT in patients with R/R DLBCL is not well established. Methods A retrospective analysis was carried out using the Mayo database across all three sites. It included all patients between 18-75 years of age who were diagnosed with de-novo DLBCL and underwent first auto-HCT for R/R disease. Patients must have received salvage treatment and shown chemotherapy sensitive disease. Patients with transformed DLBCL or other variants and those who underwent auto-HCT in first complete remission for high risk disease were excluded. Patients who had less than a partial response at time of transplantation and still underwent auto-HCT were also excluded. Primary endpoints included overall survival (OS); relapse and relapse-free survival (RFS). Continuous variables were summarized as mean (standard deviation) and median (range). Categorical variables were reported as frequency (percentage). Continuous baseline variables were compared between GCB and non-GCB using Wilcoxon rank sum test and categorical baseline variables were compared with Chi-squared test. Kaplan-Meier method was used to estimate 5 and 10-year rates of freedom from long-term events and draw corresponding survival curves. Multivariate Cox regression models were used to evaluate the impact of cell of origin on long-term survival after adjusting for baseline factors. All tests were two-sided with alpha level set at 0.05 for statistical significance. Results A total of 357 patients underwent auto-HCT between 2005 and 2018. Cell of origin was determined for 284 patients and these were included in the analysis. Median age was 61 (range: 19-78) years, and 64% patients were male. GCB and non-GCB patients did not differ significantly with regards to baseline factors (Table 1). During a median follow up of 1.7 years, 139 patients died, 151 had relapse and 175 either died or had relapse. Five year OS for GCB patients versus (vs) non-GCB was at 44% vs 64% (p=0.004) (Figure 1); relapse was at 67% vs 49% (p=0.012) and RFS was at 28% vs 50% (p=0.003). The difference between GCB and non-GCB groups remained statistically significant in multivariate analysis, with GCB patients 60% more likely to die and 50% more likely to experience relapse compared to non-GCB patients. The only other factor that retained significance in multivariate analysis for both endpoints was response at the time of transplant (Table 2A-C). Conclusions In this analysis, GCB DLBCL results in worse OS and higher relapse vs. non-GCB DLBCL following an auto-HCT. It is unclear if relapse/progression of GCB subtype after front-line therapy alters its natural history into a more aggressive disease. Disclosures Ansell: Trillium: Research Funding; ADC Therapeutics: Research Funding; Affimed: Research Funding; Bristol Myers Squibb: Research Funding; AI Therapeutics: Research Funding; Takeda: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding. Foran:Xencor: Research Funding; Trillium: Research Funding; Takeda: Research Funding; Kura Oncology: Research Funding; Aptose: Research Funding; Aprea: Research Funding; Actinium: Research Funding; Boehringer Ingelheim: Research Funding; Abbvie: Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Revolution Medicine: Consultancy; H3Biosciences: Research Funding; Agios: Honoraria, Research Funding. Tun:Celgene: Research Funding; Mundipharma: Research Funding; Curis: Research Funding; TG Therapeutics: Research Funding; Acrotech: Research Funding; DTRM Biopharma: Research Funding; Bristol-Myers Squibb: Research Funding. Kharfan-Dabaja:Daiichi Sankyo: Consultancy; Pharmacyclics: Consultancy.

AbstractIntroductionLenalidomide maintenance, commonly prescribed in the postautologous transplantation (AHCT) setting for multiple myeloma (MM), is associated with development of secondary primary malignancies (SPM). Proteasome inhibitor maintenance (PIM) has also been evaluated in MM. We conduct a systematic review/meta‐analysis to assess the efficacy of PIM in MM.MethodsPerforming a comprehensive search of the medical literature using PubMed/Medline and EMBASE on September 11, 2019, we extracted data on clinical outcomes related to benefits (OS, PFS, and depth of hematologic response [DOHR]) and harms (SPM and adverse events). 2144 references were identified; three studies were eligible for inclusion.ResultsA total of 1760 patients were included in the analysis; 507 patients received bortezomib and 395 received ixazomib maintenance. Control arms were either placebo (n = 261) or thalidomide (n = 358). PIM did not improve OS (HR 0.88, 95% CI 0.73‐1.05, P = .15) but improved PFS (HR 0.77, 95% CI 0.69‐0.86, P ≤ .00001) and DOHR (HR 0.88, 95% CI 0.79‐0.98, P = .02) compared with control. There were no significant differences between PIM and control regarding SPM (p = NS) and ≥grade 3 peripheral neuropathy (PN) (p = NS).ConclusionsPIM following AHCT in MM improves PFS and DOHR without an increase in development of SPM or severe PN compared with placebo/thalidomide.

Background: Sickle cell disease (SCD) is an inherited hemoglobinopathy which affects over 300,000 children born each year worldwide. In spite of improvement in supportive care in recent years, there is still a lack of effective treatment options. SCD leads to debilitating and cyclic episodes of erythrocyte sickling with progressive organ injury, contributing to lifetime morbidity and shortened life expectancy. Allogeneic HCT (allo-HCT) is a potentially curative therapy for SCD because engraftment is associated with resolution of the clinical phenotype of the disease and abrogation of its complications. Medical literature on allo-HCT for SCD is largely limited to children. Recent studies have evaluated the efficacy of allo-HCT in the adult population. Here, we conduct a systematic review/meta-analysis to assess the totality of evidence pertaining to the efficacy (or lack thereof) of allo-HCT in children and adults. Materials and methods: We performed a comprehensive search of the medical literature using PubMed/Medline, EMBASE and Cochrane library on July 3rd, 2019. We extracted data on clinical outcomes related to benefits (overall [OS] and disease free/event free survival [EFS/DFS]) and harms (non-relapse mortality [NRM] and graft failure [GF]), independently by two authors. Our search strategy identified 1001 references but only 30 studies (n= 1995 patients) were included in this systematic review/meta-analysis. We also performed a sub analysis on clinical outcomes for studies that included only pediatric patients (defined as <18 years) and those in patients ≥18 years of age. Results: Median age for patients enrolled in all the studies was at 10 years. Recurrent veno-occlusive crises represented the most common indication for allo-HCT followed by acute chest syndrome and stroke; nevertheless, most patients had more than one indication. Matched related donors (MRD) were the most common donor source (93%). Bone marrow was the most common source of hematopoietic stem cells (77%). Majority of patients underwent conditioning with myeloablative regimens (77%). Pooled OS rates (n=29 studies, 1681 patients) after allogeneic HCT was 95% (95%CI=93-96%) with low heterogeneity (I2=6.4%) among included studies (Figure 1). Pooled EFS/DFS rates (n=29 studies, 1894 patients) post-allografting was 90% (95%CI=87-93%) with moderate heterogeneity (I2=54%). Pooled NRM rates from 30 studies (1995 patients) was 4% (95%CI=2-6%) with low heterogeneity (I2=29.4%). Pooled GF rates from 28 studies (1851 patients) was 4% (95%CI=2-6%) with moderate heterogeneity (I2=55%). A subset analysis specifically for pediatric patients (n= 11 studies, 1009 patients, median age at 9.7 years) showed a pooled OS rate of 96% (95%CI=94-97%) with low heterogeneity (I2=0%); and for adult patients (n=3 studies, 51 patients, median age at 33.4 years) the pooled OS was 94% (95%CI=80-100%) with moderate heterogeneity (I2=52%). Pooled EFS/DFS for pediatric patients (n= 11 studies, 1009 patients) was at 89 %( 95%CI=84-93%) with moderate heterogeneity (I2=55.1%); and for adult patients (n=2 studies, 30 patients) was at 95% (95%CI=83-100%) with high heterogeneity (I2=96.5%). Pooled NRM from 10 studies with pediatric patients (281 patients) was at 6 % (95%CI=3-10%) with low heterogeneity (I2=0%); and from 3 studies with adult patients (51 patients) was at 1% (95%CI=0-7%) with low heterogeneity (I2=15.1%). Pooled GF from 10 studies with pediatric patients (281 patients) was at 3 % (95%CI=1-7%) with moderate heterogeneity (I2=40%); and from 2 studies with adult patients (30 patients) was at 5% (95%CI=0-17%) with high heterogeneity (I2=95.4%). Conclusions: The results of our systematic review/meta-analysis show excellent OS, EFS/DFS in children and adults undergoing allo-HCT with pooled OS rates exceeding 90%. The main limitation to offering an allo-HCT in SCD remains the availability of a suitable donor as 85% of patients meeting criteria do not have a MRD. We anticipate that with emergence of haploidentical transplantation the number of allo-HCT will increase in the future. GF remains a significant concern in this population and future studies should focus on novel immune suppression strategies to help reduce GF. Disclosures Kharfan-Dabaja: Pharmacyclics: Consultancy; Daiichi Sankyo: Consultancy.

Abstract Background: Therapeutic advancements have led to significant improvement in outcomes for MM patients. Revised diagnostic criteria from International Myeloma Working Group focus on initiating treatment before the onset of end-organ damage. Thus, timeliness of initial therapy can significantly improve patient morbidity and outcomes. Such an analysis has not been reported for MM. Methods: We analyzed patients diagnosed with MM between 2004-2015 from the National Cancer Database (NCDB). Patients who received systemic treatment any time within the first year of diagnosis were included; those treated later than one year were considered possibly initially diagnosed with smoldering myeloma and hence, excluded. Time to initial treatment was divided into centiles with the 4 centiles analyzed being 0-7 days, 8-18 days, 19-37 days and >37 days. We performed univariate and multivariate analyses to compare sociodemographic and clinical factors influencing patient distribution across these timeliness categories and trends over time. Results: A total of 53,665 patients were included with 15,282 in 0-7 days, 12,462 in 8-18 days, 12,723 in 19-37 days and 13,198 in the >37 days treatment categories. Distribution across these centiles over time is shown in Figure. Univariate analyses showed a significant difference in distribution across the timeliness categories by year of diagnosis, patient age, gender, race/ethnicity, education level, insurance type, comorbidity score, treatment facility type, geographical location and distance to treating facility (all p<0.001) but no effect of income level. Multivariate analysis showed that there was a significantly higher likelihood of being in 4th centile (>37 days to treatment) for women (p<0.001), African Americans (p<0.001) or Hispanics (p=0.03; reference: Whites) or diagnosed in more recent years (p<0.001). Patients were less likely to be in the 4th centile if they were ≥80 years (HR 0.89, 95% CI 0.81-0.98, p=0.02), had >0 Charlson comorbidity score (p<0.001), were uninsured (p=0.02) or had Medicaid (p=0.03) as compared to having private insurance, were in non-community treatment facilities or geographical location other than Northeast (p<0.001). Patient education, income level or distance from treating facility was no longer significant. Conclusions: Several factors were found to affect timeliness of treatment in MM. We noted relatively faster time to initial treatment in elderly, uninsured or those who were treated in academic/comprehensive cancer programs but a delay in treatment for women and racial/ethnic minorities among other factors. These factors need to be addressed for equitable access and treatment practices and to realize improved outcomes for all. Figure. Figure. Disclosures Ailawadhi: Amgen: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Takeda: Consultancy; Pharmacyclics: Research Funding.

Abstract INTRODUCTION: Significant burden of pain syndromes are reported in patients with hematological malignancies undergoing HSCT mostly due to underlying disease and associated treatments. Opioid analgesics and benzodiazepines are routinely used for symptomatic management in this patient population. The use of narcotic analgesics and benzodiazepines in non-transplant hospitalized patients has been shown to adversely affect health related outcomes such as length-of-stay (LOS), falls and other complications. However, there is a significant knowledge gap regarding the patterns of opioid and benzodiazepine use and their impact on health outcomes in HSCT patients. METHODS: We identified 275 patients from the year 2015-2018 who underwent HSCT (allogeneic and autologous transplants) at our center for a variety of hematological malignancies. Opioid exposure was defined in three groups of patients 1) Opioid naïve: those did not report prior use of opioid at admission and who were not prescribed opioid during hospitalization, 2) Previous Opioid users: those who reported active use of opioid at admission and continued during hospitalization 3) New Opioid users: Patients who did not report opioid use at admission but were prescribed opioid during hospitalization. Multivariable analysis was performed to identify differences in opioid status, opioid use, benzodiazepine use, disease diagnosis, Karnofsky score, gender, age, race, and marital status with associated complications (Poisson regression), emergency department visits (Logistic Regression) and length of stay (Ordinal Logistic Regression) Figure 1 and Figure 2. RESULTS: The median age of patients was 59 (range: 25-74 ) years with slight male predominance (57%). Patients undergoing autologous transplants for multiple myeloma (MM) comprised 48% of the population. The majority (72 %) were exposed to opioid during hospitalization. Ninety two percent of the opioid naïve population (28% of the total population) underwent autologous transplant. Conversely, 36% of patients undergoing autologous transplants never received opiates during hospitalization as compared to 7% of those who received an allogeneic transplant. Median morphine milligram equivalent daily dose was 3.1 mg. Median diazepam equivalent daily dosage in patients that were opiate exposed was 2.07 milligram. Of the total transplant population, 55% received benzodiazepine concurrently with opiates during hospitalization. 76 % of the population was exposed to both opioid and benzodiazepine. Twenty five percent of those who were exposed to opioid did not receive benzodiazepines. Sixty four percent of the MM patients were exposed to opioid of which majority (59%) were previous opioid users. Of the non-MM patients undergoing HSCT, 80% were exposed to opioid of which 36% were previous opioid users and 64% were new users. A wide range of complications from neutropenic fever to death, were seen in 89% of all patients (opioid users and non-users) but all the falls occurred in patients who were on opioid medications. Autologous transplant recipients had higher odds of having a greater number of complications compared to Allogeneic transplant patients (OR 1.25, 95% CI: 1.01 - 1.55, p=0.04), as well as a reduced odds of having a medium or high length of stay (OR 0.03, 95% CI: 0.02 - 0.07). Of the opioid naïve patients, 6% presented to the ED within 30 days of discharge versus 15% of those that were exposed to opiates during hospitalization. Benzodiazepine use at admission for HSCT was associated with greater odd of presenting to ED within 30 days of discharge (OR 3.94, 95% CI: 1.55-10.04) and this was more significant in patients with MM (OR 4.08, 95% CI: 1.01-16.44). Finally, we also saw a trend towards longer stay in patients who were exposed to opioids as compared to opioid naïve (40% vs. 17%). CONCLUSION: Our study, albeit limited due to its retrospective design, is among the first to report the patterns of use and the impact of opioids and benzodiazepines in patients undergoing HSCT. Our results indicate that the use of these medications is frequent in this population and as in the non-transplant hospitalized patients and is associated with more emergency room visits post discharge, along with other potentially adverse outcomes. Disclosures Kharfan-Dabaja: Incyte Corp: Speakers Bureau; Seattle Genetics: Speakers Bureau; Alexion Pharmaceuticals: Speakers Bureau. Ailawadhi:Amgen: Consultancy; Pharmacyclics: Research Funding; Celgene: Consultancy; Takeda: Consultancy; Janssen: Consultancy.

Abstract INTRODUCTION: Treatment of chronic lymphocytic leukemia (CLL) has expanded significantly with the approval of multiple small molecule inhibitors. This is of great significance for patients with adverse cytogenetic features who tend to respond poorly to standard chemo-immunotherapy (CIT). While single agent ibrutinib and venetoclax (V) have shown high rates of overall response, complete remission and minimal residual disease (MRD) eradication rates remain low. This argues for further testing and development of various combination strategies. The MURANO trial compared venetoclax and rituximab (VR) versus bendamustine and rituximab (BR) in patients with relapsed/refractory CLL reporting clear superiority of VR over BR. MRD rates in the bone marrow were reported to be 27.3% for VR versus 1.5% for BR. Given much higher rates of MRD eradication with combination of small molecule inhibitors and monoclonal antibodies (mAb) compared to standard CIT, we performed a comparative investigation into the direct and immune-mediated cytolytic effects of VR versus V + Obinutuzumab (O, type II anti-CD20 mAb) in primary CLL cells and B-lymphoid cell lines. METHODS: CD19+ B-cells were isolated from PBMCs of CLL patients (N=3). For all experiments using primary CLL cells, concentration of VR and VO was 3nM (V) and 10ug /ml (R, O), respectively. For cell lines, VR and VO was used at 5uM (V) and 10ug /ml (R, O), respectively. Apoptosis was determined by annexin-V/PI staining followed by flow cytometry. Antibody-dependent cell-mediated cytotoxicity (ADCC) induced by VR and VO was assessed in Calcein AM labeled CLL cells or cell lines co-cultured with healthy donor PBMCs (E:T ratio, 40:1); complement-dependent cytotoxicity (CDC) was measured using 10% serum from a healthy human donor. RESULTS: We assessed the ability of V+/-O or V+/-R to induce apoptotic cell death in the CD20+ BCWM.1 cell line (Waldenström's macroglobulinemia [WM] phenotype) and the MEC-1 cell line (B-PLL phenotype); with CD20- RPCI-WM1 (WM cells, negative control). Notably, Bcl-2 protein is expressed in all the aforementioned cell lines. We observed that single agent V, O and R induced ~30%, 61% and 13.64% annexin V/PI positivity in BCWM.1 cells, respectively. However, a significant degree of cell death was noted in VO-treated cells (~74%) compared to VR-treated cells (~40%) (p<0.01). Next, we examined for apoptosis in MEC1 cells and noted a similar trend; where the VO combination induced markedly more cell death (~71%) than VR (~57%). Contrastingly, in RPCI-WM1 cells neither single agent O or R could elicit >12% annexin V/PI positivity and where the addition of V increased apoptosis by only 3 - 4%. We also examined the apoptotic potential of VO or VR in tumor cells from low, intermediate and high-risk CLL patients. In low and intermediate-risk CLL cells from low and intermediate-risk patients, V alone induced ~30% cell death, which increased significantly with the addition of O (VO) to between 48 - 52%. Contrastingly, the combination of VR did not induce more than 29 - 32% apoptosis. In CLL cells from high-risk patient, we noted that exposure to single agent V induced ~ 28% cell death and in VO-treated cells, this number increased to 47%. We also examined for ADCC and CDC in the same cell lines and primary CLL cells. Despite considerable variability, single agent O and VO treatment of tumor cells resulted in greater ADCC than VR treatment. By contrast, in single agent R or VR-treated cells, more CDC was observed. CONCLUSION: Our preliminary investigation in VR- and VO-treated cell lines and primary CLL cells suggests the VO combination may be superior to VR in induction of direct tumor cell death. Mechanistic experiments underway will provide further insight and can aid in design of future VO-based clinical studies in CLL. Disclosures Ailawadhi: Pharmacyclics: Research Funding; Takeda: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Amgen: Consultancy.

Abstract Background: DLBCL is the most common adult NHL and despite significant advancements, outcomes in ethnic minorities remain suboptimal. Factors responsible for these disparities in ethnic minorities, especially variability in clinical and pathological features with evaluation of patient-level data have not been studied. Methods: A multi-institutional database of DLBCL patients seen at Mayo Clinic in Florida, University of Miami and University of Southern California between 1996-2016 was developed. Patient demographics, clinical disease characteristics and details of DLBCL immunophenotype [CD10, MUM1, BCL6 (Han's classification), Ki 67, MYC, BCL2) were reviewed. Comparisons between Hispanic and Non-Hispanic patients were made by Chi-square, Fischer's exact and Signed rank tests, where applicable. Patients with missing data on a certain feature were not included in the statistical analysis of that specific characteristic. Results: A total of 966 DLBCL patients with 69 Hispanics and 752 non-Hispanics were identified. These included 52% males (N=36) and 48% females (N=33) in Hispanics versus 58% males (N=436) and 42% females (N=316) in Non-Hispanics (p=0.35). Median age at diagnosis was significantly lower at 61 years (range 27-89) in Hispanics versus 66 in non-Hispanics (p=0.014). Extranodal disease was seen significantly more commonly in Hispanics (74%) than in non-Hispanics (60%) (p=0.037). There was no significant difference in disease stage at presentation between the two cohorts (p=0.189) although the proportion of patients with stage III and IV disease was higher among Hispanics (80.4%) as compared to non-Hispanics (68.5%). Similarly there was no significant difference in presence of primary CNS DLBCL at diagnosis between the two groups (p=0.74). GCB phenotype per the Hans' classification was seen in 59% (N=29) in both, Hispanics and Non-Hispanics (N=241) (p=0.99). Similarly, the median ki67 index of 80% was seen in both cohorts (p=0.48). MYC was positive in 59% in Hispanics versus only 37.5% in non-Hispanics (p=0.024). BCL2 expression by itself and also combined BCL2 and MYC double expression were not significantly different between the two groups (p=0.58 and p=0.11, respectively). Median overall survival (OS) was 22.5 months in Hispanics compared 54.9 months in Non-Hispanics (p<0.0001) (Figure 1). Conclusion: Survival outcome disparities in racial and ethnic minorities have been previously reported from population-based analyses. Lack of patient-level clinical data makes these analyses hypothesis generating, but not conclusive. We confirmed some prior findings including younger age at diagnosis for Hispanics with DLBCL. We also reported greater incidence of extranodal as well as stage III or IV disease at the time of presentation among Hispanics which may contribute to poor outcomes in this population. From DLBCL pathology standpoint, we found increased expression of MYC among Hispanics but no other significant immunohistochemical differences including double expression or non-GCB phenotype. The inferior OS despite uniform treatment practices at large Cancer Centers suggest multifactorial influences on patient outcomes which may at least in part include some of the differences we report here. Disclosures Ailawadhi: Pharmacyclics: Research Funding; Janssen: Consultancy; Takeda: Consultancy; Celgene: Consultancy; Amgen: Consultancy.

Abstract INTRODUCTION: Autologous hematopoietic stem cell transplantation can heavily impact the quality of life (QOL) of an individual. However, this procedure may be the only hope for a cure or a longer life for some individuals. When these patients develop severe neutropenia during transplantation, protective isolation is recommended to reduce the risk of infection. During protective isolation, patients may be confined to their hospital room which can decrease their physical activity. For autologous hematopoietic stem cell receipts (AHSCR), severe neutropenia may last several days to weeks. During this time, patients often experience social isolation, emotional encumbrances and also physical deconditioning.Data is inconsistent whether protective isolation does reduce the incidence of infections. In this study, we sought to investigate the impact of physical activity during hospitalization on Quality of Life in AHSCR with severe neutropenia using the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) questionnaire. METHODS: We conducted a prospective observational study of 15 patients admitted to Mayo Clinic Florida during November 2017 to May 2018 for autologous hematopoietic stem cell transplantation, wherein we monitored the activity of each patient during hospitalization by recording the number of steps taken each day by using an activity tracker worn by the patient. Informed consent was obtained on admission before enrolling patients. Patients completed a Quality of Life (QOL) questionnaire (FACT-BMT version 4) on admission and prior to discharge from the hospital. RESULTS: Of the 15 patients that were enrolled, 5 walked ≤ 100 steps/day (group A, median, 71) and 10 walked > 100 steps/day (group B, median, 406). While there was no difference in the median time to engraftment and length of hospital stay, the mean QOL score decreased from 89.2 on admission to 81.4 on discharge in less active neutropenia patients compared to the ones who were more active. (Table 1; Figure 1) CONCLUSION: Lack of physical activity decreases QOL in AHSCR. During hospitalization, AHSCR should be encouraged to increase their activity to improve QOL. Having an activity tracker may make it easier for patients to monitor their activity, and thus lead to a better QOL. Figure. Figure. Disclosures Sher: Affimed: Research Funding. Ailawadhi:Pharmacyclics: Research Funding; Janssen: Consultancy; Takeda: Consultancy; Amgen: Consultancy; Celgene: Consultancy.

Abstract Background: CLL is the most common leukemia diagnosis in adults and its treatment has undergone significant change from chemotherapy, to immunotherapy and now targeted kinase inhibitors, leading to improved overall survival (OS). With improving survivorship, SPMs can occur but an in-depth analysis of risks and trends of SPMs in CLL survivors is lacking. We performed a population-based analysis to evaluate this. Methods: Patients in the Surveillance, Epidemiology and End Results (SEER) database diagnosed with CLL between 1973-2015 were included. Due to variation in management techniques over time, the cohort was divided in four time periods: 1973-1982, 1983-1992, 1993-2002 and 2003-2015. We evaluated differences in risk for SPMs among CLL survivors compared to risk of individual malignancies expected in the general population during these time periods and studied the effect of demographics and time since CLL diagnosis. Results: Over a nearly 270,000 person-year follow up, 6,467 new SPMs were diagnosed with a standardized incidence ratio (SIR) of 1.2 (95% CI 1.17-1.23), which resulted in a 39 excess cancers per 10,000 population. The CLL survivors had a 20% overall increased risk of developing SPMs (excluding non-squamous skin cancer) compared to the general population. The risks for both solid (SIR 1.15 CI 95% 1.12-1.18) and hematological malignancies (SIR 1.61 95% CI 1.5-1.73) was higher than the expected in the general population. However, the risk for individual cancers was heterogeneous. The tumors associated with the highest risk were Hodgkin lymphoma (almost 8 times higher), Kaposi Sarcoma (4 times), non-epithelial skin cancers (4 times), salivary gland cancer (3 times) and acute lymphocytic leukemia (3 times). In contrast, tumors in the hepatobiliary system, female breast and female genital system were associated with a lower risk than the general population. The highest SIR across the study periods was observed in the younger population (ages 15-49). Although the risk increased in all ethnicities, it was statistically significant only in Caucasians. There was no gender-wise difference in SIR during any of the four time periods. A statistically significant increase in SIR was observed for both men and women from 1973-1982 to 2003-2015. This was mostly due to an increase in risk of hematological malignancies from 1.08 early in the study to 2.56 in the most recent study period. The SIR in solid tumors did not change significantly over time; in absolute terms, however, lung carcinoma contributed the most to the excess risk, followed by non-epithelial skin cancers and non-Hodgkin's lymphoma. The risk of developing a SPM was higher for the CLL survivors during most of the latency periods, but it was statistically significant during the 2-5 months and 12-59 months after diagnosis. A multivariate analysis was conducted to evaluate the impact of period of diagnosis on the development of SPMs among these patients. After adjusting for gender, ethnicity, radiation therapy, chemotherapy, and age at diagnosis of CLL, patients diagnosed with CLL in the most recent time period were at 45% higher risk of developing SPMs as compared to the patient diagnosed during 1973-1982 (Hazard ratio(HR) =1.45 95%CI:1.34-1.6, p<0.001). Moreover increased HRs were also observed for 1983-1992 and 1993-2002 time periods (Fig. 1) Conclusions: With improving therapeutics for cancer treatment, survivorship is improving as well and the risk of SPMs needs to be better understood and addressed. This is truer for CLL, where majority of patients have a favorable survival. The risk of SPMs was 20% higher in CLL survivors than in the general population and was most prominent in the survivors aged 15-49 years at the time of CLL diagnosis. The risk of individual malignancies may be heterogenous but there has been an increase in risk of SPMs over time, mainly due to an increase of secondary hematological malignancies in recent years. Active survivorship plans and long-term surveillance for SPMs is crucial for improved outcomes of patients with a history of CLL. Disclosures Ailawadhi: Janssen: Consultancy; Celgene: Consultancy; Amgen: Consultancy; Takeda: Consultancy; Pharmacyclics: Research Funding.