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PURPOSE To present primary and final analyses from the randomized, double-blind, placebo-controlled, phase III iNTEGRATE study, which evaluated the safety and efficacy of ibrutinib with prednisone in previously untreated patients with chronic graft-versus-host disease (cGVHD). METHODS Patients (age ≥ 12 years) with newly diagnosed moderate or severe cGVHD, requiring systemic corticosteroid therapy, and with no prior systemic treatment for cGVHD were randomly assigned 1:1 to receive ibrutinib 420 mg once daily plus prednisone, starting at 1 mg/kg once daily or placebo plus prednisone. The primary end point was response rate at 48 weeks according to 2014 National Institutes of Health Consensus Development Project Criteria. Other end points included event-free survival, duration of response, time to withdrawal of immunosuppressants, improvement in Lee cGVHD Symptom Scale score, overall survival (OS), and safety. RESULTS Ninety-five and 98 patients enrolled in the ibrutinib-prednisone and placebo-prednisone arms, respectively. At 48 weeks, response rates were 41% (ibrutinib-prednisone) and 37% (placebo-prednisone; P = .54). At 33 months of follow-up, median duration of response was 19 months (ibrutinib-prednisone) and 10 months (placebo-prednisone; P = .10). Median event-free survival was 15 months (ibrutinib-prednisone) and 8 months (placebo-prednisone; hazard ratio, 0.76; 95% CI, 0.54 to 1.1; P = .11). Improvement in overall Lee cGVHD Symptom Scale was 43% (ibrutinib-prednisone) and 31% (placebo-ibrutinib; P = .07). Median OS was not reached in either arm. The 24-month Kaplan-Meier OS estimates were 80% for both arms (hazard ratio, 1.06; 95% CI, 0.59 to 1.90). Grade ≥ 3 serious adverse events occurred in 49% (ibrutinib-prednisone) and 47% (placebo-prednisone) of patients. CONCLUSION There was no statistical difference observed in the primary and secondary end points with ibrutinib-prednisone treatment. No new safety signals were observed with ibrutinib treatment in previously untreated patients with cGVHD. The primary end point of iNTEGRATE was not met.

The relative efficacy of autologous hematopoietic cell transplant (auto-HCT) vs chimeric antigen receptor T-cell (CAR-T) therapy in patients with diffuse large B-cell lymphoma (DLBCL) who achieve a partial remission (PR) after salvage chemotherapy is not known. Using the Center for International Blood & Marrow Transplant Research registry database, we identified adult patients with DLBCL who received either an auto-HCT (2013-2019) or CAR-T treatment with axicabtagene ciloleucel (2018-2019) while in a PR by computed tomography or positron emission tomography scan. We compared the clinical outcomes between the 2 cohorts using univariable and multivariable regression models after adjustment for relevant baseline and clinical factors. In the univariable analysis, the 2-year progression-free survival (52% vs 42%; P = .1) and the rate of 100-day nonrelapse mortality (4% vs 2%; P = .3) were not different between the 2 cohorts, but consolidation with auto-HCT was associated with a lower rate of relapse/progression (40% vs 53%; P = .05) and a superior overall survival (OS) (69% vs 47%; P = .004) at 2 years. In the multivariable regression analysis, treatment with auto-HCT was associated with a significantly lower risk of relapse/progression rate (hazard ratio = 1.49; P = .01) and a superior OS (hazard ratio = 1.63; P = .008). In patients with DLBCL in a PR after salvage therapy, treatment with auto-HCT was associated with a lower incidence of relapse and a superior OS compared with CAR-T. These data support the role of auto-HCT as the standard of care in transplant-eligible patients with relapsed DLBCL in PR after salvage therapy.

Secondary hemophagocytic lymphohistiocytosis (HLH) is a life-threatening immune dysregulation disorder. Use of chimeric antigen receptor T-cell therapy (CAR-T) is associated with cytokine release syndrome (CRS), Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS) and secondary HLH. However, application of HLH scoring systems (H-score, HLH-2004 criteria) are not validated in this setting. We analyzed the utility of applying the H-score and the HLH-2004 criteria to identify patients with possible HLH post-CAR-T for Relapsed/Refractory Diffuse Large B-cell Lymphoma. Only two of four patients with post CAR-T HLH met five or more of the diagnostic criteria for HLH by HLH 2004 criteria. In contrast all four post CAR-T HLH patients had a high H-score (169); however, an additional ten patients that did not have HLH also had a high H-score. Thus, in this patient population, both scoring systems were demonstrated to have low prognostic significance in differentiating between high grade CRS and HLH.

Aim: Characterize follicular lymphoma (FL) treatment patterns among elderly patients using a dataset with longer follow-up time. Materials & methods: Using the linked Surveillance, Epidemiology and End Results-Medicare data, we identified patients diagnosed with FL between 2000 and 2013 with claims data until 2014. We investigated the treatments received and assigned them to lines of treatment. Results: We identified 10,238 elderly patients. Over a 4.7-year median follow-up, 78% of the patients received at least first-line treatment. Fewer individuals received second-line (47%) and third-line (30%) treatments. RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone), RCVP (rituximab, cyclophosphamide, vincristine and prednisolone) and rituximab monotherapy were the most common treatment regimens. Conclusion: One in five elderly patients did not receive FL-directed therapy. The most common treatment regimens were limited to RCHOP, RCVP and rituximab monotherapy.

Background: Nonmyeloablative (NMA) and reduced-intensity conditioning (RIC) regimens are offered for patients with hematologic malignancies requiring allogeneic stem cell transplantation (HSCT) but are not candidates for myeloablative conditioning (MAC). The intensity of the conditioning regimen (CR) is important and contributes to the ability of HSCT to provide a cure. There is no consensus regarding the best RIC regimen and efficacy is not equal amongst RIC regimens. The combination of 2 days of intravenous Busulfan (total of 6.4 mg/Kg) and Fludarabine (total of 120-160 mg/m2) (Flu/Bu2) has been validated and widely adopted. While this regimen is well tolerated, relapses are common and remain the leading cause of death. Total body irradiation (TBI) has been widely used in the CR and provides the advantage of potent anti-cancer effect, immunosuppression and the ability to reach certain 'sanctuary sites' for chemotherapy (i.e. CNS). The 2 most commonly used TBI levels are 1200 cGy in MAC regimens and 200 cGy in NMA and RIC regimens. We hypothesize that the addition of 400 cGy (200 cGy two fractions per day, 6 hours apart) TBI to Flu/Bu2 will reduce the relapse rate without increasing its toxicity. In this retrospective study, we compared the safety and efficacy of Flu/Bu2/TBI400 with Flu/Bu2 CR amongst a diverse group of hematologic diseases. Methods: From 2006 to 2018, 137 adult patients with different hematological diseases were treated using one of two RIC regimens, either Flu/Bu2/TBI400 or Flu/Bu2 followed by HSCT from HLA-matched related or unrelated donors. The primary endpoint was OS defined as the time from the date of transplant to death from any cause. The secondary endpoints included PFS, relapse rate, cumulative incidence of relapse (CIR), non-relapse mortality (NRM), causes of death, aGVHD, cGVHD and engraftment. PFS was defined as the time from the date of transplant to disease progression as documented by the treating physician, based on pathological, imaging or clinical findings of the individual disease, or death from any cause. NRM was defined as time of death without evidence of progressive disease with relapse or progressive disease as a competing risk event (data not shown in the abstract). Relapse was defined as progression or disease relapse with NRM as a competing risk event. These endpoints were censored at the time of last follow-up. Results: A total of 137 patients were included in this study. 74 patients were treated with Flu/Bu2/TBI400 and 63 patients were treated with Flu/Bu2. The 2 groups were comparable in terms of patient-, disease- and transplant-related characteristics; however, Flu/Bu2/TBI400 patients had a higher HCT-CI score and a lower KPS. CNI-MTX GVHD prophylaxis was used in a higher proportion in Flu/Bu2/TBI400. Most of the Flu/Bu2 transplants occurred from 2006 to 2012. The median age was 62 in both groups and patients had comparable disease type distribution and DRI (Table 1). The median follow-up time was 4.62 years. Flu/Bu2/TBI400 showed improvement of PFS over Flu/Bu2; the 5-year PFS was 50% in the TBI arm vs. 34% in the no-TBI arm (p=0.06 of marginal statistical significance). There was a numerical improvement of OS in favor of the TBI arm but this was not statistically significant; The 5-year OS was 53% with TBI vs. 39% without TBI (p=0.13). Cumulative incidence of relapse was not different between the 2 groups (p=0.29), see figures 1, 2 and 3. There was no difference in aGVHD incidence between the 2 groups (p=0.21). The TBI arm had significantly lower incidence of cGVHD compared to no-TBI arm (29% vs. 54%, p=0.005). Advanced DRI, grade III-IV aGVHD, cGVHD, use of ATG and MUD were associated with worse OS (univariate analysis). The same factors, with the exception of cGVHD, were associated with worse PFS. Multivariable Cox regression model revealed that grade III-IV aGVHD was associated with worse OS (p=0.001) while advanced DRI was associated with marginally inferior OS (p=0.07) (Table 2). Conclusion: This is the largest retrospective study of RIC Flu/Bu2/TBI400 regimen for HSCT with a median follow-up approaching 5 years. Our data suggests that RIC Flu/Bu2/TBI400 is safe and efficacious for different hematological malignancies. When compared to Bu/Flu2 without TBI, Flu/Bu2/TBI400 had lower incidence of cGVHD and showed a strong trend towards improved PFS and OS though not statistically significant at this time. Grade III-IV aGVHD was associated with poor OS in both groups. Disclosures Hardy: Incyte Corporation: Other: Advisory Board Member; Kite/Gilead: Other: Advisory Board Member; American Gene Technologies: Other: DSMB Member.

There is limited information on the cost burden associated with follicular lymphoma (FL) and how it compares to other non-Hodgkin lymphoma (NHL) subtypes. We examined the direct medical costs associated with FL and estimated the incremental 3-year cost of FL compared to other NHL subtypes. Using the linked Surveillance, Epidemiology and End Results-Medicare dataset, we identified 16,691 NHL patients aged 66 years or older who were diagnosed with NHL between 2007 and 2013. The mean 3-year cost among the full NHL sample was $120,120 (standard error (SE) 839). The mean 3-year cost per patient was $114,443 (SE 1738) for FL and $121,402 (SE 950) for non-FL subtypes. The incremental 3-year cost of FL compared to non-FL was US$-5458 (95% confidence interval: US$-9325 to US$-1590). Longitudinally, FL was less costly than other NHL subtypes in the first year only, and became more expensive in the second and third years.

Background: Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are known complications of chimeric antigen receptor T-cell (CAR-T) therapy. These clinical syndromes develop as a result of CAR-T activation, proliferation, and tumor lysis with resultant cytokine secretion. In prior reports of CD19 CAR-T therapy patients, those who developed ICANS showed evidence of endothelial activation and disruption of the blood-brain barrier as a result of cytokine release while only approximately one-third demonstrated changes on Brain MRI (Gust et al. Cancer Discov 2017). As such, further predictive markers and studies are needed to identify patients at risk for ICANS to allow for expedited management and improved outcomes. Herein we report a single-center analysis exploring glycolytic activity on PET/CT and the association with clinical outcomes for patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) after CAR-T therapy. Methods: An organ-based evaluation of uninvolved sites was conducted in R/R DLBCL patients (n=32) who underwent CD19 CAR-T therapy with evaluable PET/CT imaging at baseline immediately prior to CAR-T therapy and at 30 days post-infusion (D+30). All patients in this analysis were treated with axicabtagene ciloleucel as standard of care therapy after 2 or more lines of therapy. Tumor metabolic volume (TMV) and mean standard uptake value (SUVmean) of various organs were quantified using ROVER [Region of interest (ROI) visualization, evolution, and image registration] software (ABX advanced biochemical compounds GmbH, Radeberg, Germany). Statistical analysis was completed using STATA 14 (StataCorp. 2015. Stata Statistical Software: Release 14. College Station, TX: StataCorp LP). All tests were performed after testing the normality distribution assumption. Temporal changes were assessed using paired t-tests, and between-group analyses were completed with two-sample t-tests. Results: SUVmean increased significantly after CAR-T therapy in the following organs (D+30 v baseline pre-CAR-T PET/CT): cerebral cortex (8.23 v 7.09, p=0.036), cerebellum (6.26 v 5.56, p=0.024), basal ganglia (9.22 v 7.61, p=0.005), parotid gland (1.61 v 1.42, p=0.004), liver (2.47 v 2.17, p=0.002), spleen (2.08 v 1.84, p=0.043), and pancreas (1.76 v 1.48, p Conclusion: For patients with R/R DLBCL undergoing CD19 CAR-T therapy, significantly increased CNS glycolytic activity is seen on PET/CT at D+30 post-infusion when compared to baseline. Interestingly, these changes do not correlate with development of ICANS or lymphoma response; however, changes in cortical activity were associated with CRS grade ≥2. Overall, our findings illustrate a functional and radiographic link between cytokine release and subsequent disruption of the blood-brain barrier as quantified by increased cortical glycolysis 30 days post-CAR-T therapy. While findings are limited by small sample size, further validation in a larger data set is warranted. Disclosures Hutnick: Kite/Gilead: Other: Yescarta Speakers Bureau, Speakers Bureau. Badros:Celgene Corporation: Consultancy; Amgen: Consultancy.

7560 Background: Axicabtagene Ciloleucel (Axi-cel), an anti-CD19 CART cell therapy, achieved 58% complete response (CR) rate, in patients with relapsed refractory (r/r) LBCL on the ZUMA-1 study (Neelapu, NEJM 2017). Early response assessment (PET-CT) at day 30 is a common clinical practice. Patients with partial response (PR) at day 30 pose a therapeutic dilemma. ZUMA-1 analysis showed 1/3rd PR patients would convert to a CR. No biomarkers exist to predict eventual response. We report comprehensive PET-CT biomarker analysis on patients with PR at day 30 treated with Axi-cel for r/r LBCL. Methods: Ten patients with PR based on PET-CT imaging at day 30 were retrospectively assessed. Day 30 PET-CT was compared to baseline and a day 90 PET-CT. Global burden of disease of each patient at every time-point were quantified using Total Tumor Glycolysis (TTG) methodology as the imaging biomarker. Using adaptive-thresholding method, each lesion on FDG PET image was segmented and the following parameters were quantified: metabolic-volume (MV), SUVmax, SUVpeak, Partial-Volume-Corrected SUVmean and five other imaging biomarkers. To evaluate the effect of baseline and early imaging biomarkers to predict the subsequent burden of disease multiple regression analysis was performed (STATA 15). Results: Day 90 PET-CT assessment revealed, 4 patients had progressive disease (PD), 4 had CR, and 2 had PR. TTG of patients with PD at day 90 was 900 vs. 29 in patients with non-PD (CR, PR). The Global-SUVmean of the patients with PD at day 90 was 725 vs. 86 in patient with non-PD. Regression analysis showed early-TTG as a significant predictor of subsequent-TTG (beta-coefficient = 1.26 (0.39-2.13); P-value = 0.02; adjusted-R-squared = 0.97), while the baseline-TTG didn’t have any effect on subsequent-TTG (P-value = 0.3). Additionally, the regression analysis didn’t show any significant predictive value in SUVmean and SUVmax of baseline and day 30 scans to predict subsequent burden of disease (TTG or Global-SUVmean) with P-values > 0.8. Conclusions: Early post-axi-cel TTG, rather than baseline, can predict subsequent response to treatment. None of the SUV indices, commonly used in daily practice, were predictive of eventual response.

Introduction The PRIMA (Primary Rituximab and Maintenance) study established 2 years of maintenance rituximab (MR) as a standard of care for follicular lymphoma (FL) patients who achieve an objective response after induction chemotherapy. A 17% improvement in progression-free survival (PFS) compared with those who did not receive MR was observed. However, the decision to stop MR after 2 years was arbitrary, and the PRIMA study reports only short-term follow-up of 3 years. Longer series on FL outcomes describe ubiquitous relapse and death following recurrence. The optimal duration of MR is under investigation. Herein, we report our experience with prolonged MR in FL. Patients and Methods In this retrospective analysis, the outcome of 25 consecutive, unselected, previously untreated patients with low-grade high tumor burden FL in need for treatment is described. All patients achieved a partial or complete response to induction immunochemotherapy and received ongoing MR therapy. Results With a median follow-up of 5.0 years and 5.2 years mean duration of MR, there are no relapses. Five deaths have occurred, unrelated to lymphoma or therapy. Prolonged MR treatment has been well-tolerated. Hypogammaglobulinemia is the only observed adverse event, with only one patient requiring monthly intravenous gamma globulin infusions due to recurrent pneumonia. There has been no discontinuation of MR or refusal to remain on MR. Conclusion These provocative long-term results suggest that continuous MR beyond 2 years is safe and may be associated with prolonged PFS in patients with FL who achieve an objective response after immunochemotherapy.

Background: Sickle cell disease (SCD) is a common hemoglobinopathy, characterized by vaso-occlusive crises and affects over 100,000 people in United States. It afflicts long-lasting organ damage with a spectrum of clinical severity. Median survival for SCD is shortened to the 6th decade of life despite advances in medical care (Elmariah et al Am J Hematol 2014). Allogeneic stem cell transplant (SCT) is a potentially curative option and is increasingly considered in patients with severe symptomatic SCD. The use of SCT is limited by donor availability and treatment related complications. Several advancements in conditioning regimen and use of alternate donor source have favorably impacted the feasibility of this approach. We identified SCT performed for sickle cell disease in the Healthcare Cost and Utilization Project National Inpatient Sample (HCUP-NIS) from 2002-2014 in an attempt to identify hospitalization outcomes, factors affecting length of stay and healthcare utilization. Methods: HCUP-NIS is a 20% stratified sample of all discharges from hospitals across 46 states in the United States and incorporates weighting algorithms to predict nationwide estimates. We used International Classification of Diseases, Ninth Revision (ICD-9) procedure codes to identify HCT hospitalizations {Bone marrow (BM):41.02, 41.03, Peripheral blood (PB): 41.05, 41.08 and Cord blood (CB): 41.06} for sickle cell disease (282.5,282.6X -282.6X). We excluded patients who underwent SCT for indications other than SCD. Surveyfreq was used to calculate proportions and surveymeans was used to calculate median length of stay and hospital charges. Kruskal-Wallis test was used for non-parametric data. Chi-square for categorical data frequency, P value of < 0.05 was statistically significant. All analysis was performed using SAS 9.4. Results: Outcomes were analyzed from a total of 742 hospitalizations for SCT from 2002-2014 (table 1). Median age for stem cell transplant was 9 years. GVHD occurred in 14% of stem cell transplants. Overall, in-hospital mortality was low at 2.6% while mortality in patients who developed GVHD was 14%. Bacterial infections (including C.difficile) occurred more commonly than viral or fungal infections (table 2). Patients who developed graft vs host disease (GVHD) were also more likely to have bacterial, viral and fungal infections than those without. Pain crisis was noted in 9% of total admissions while stroke occurred in 6%. Median length of stay (LOS) was 35 days and median charges were $359,646. If GVHD developed, median LOS increased to 54 days while median charges increased to $712,324. Similarly, bacterial sepsis was associated with a longer median LOS of 63 days while median charges increased to $626,986 (table 3). Conclusions: The rate of inpatient mortality with SCT in sickle cell disease is lower than the overall inpatient mortality rate for allogeneic SCT (7%; Godara et al bbmt 2018), indicating a favorable outcome for these patients. Infections do occur commonly during the course of hospitalization, especially in association with GVHD. Length of stay is adversely impacted by occurrence of GVHD, bacterial sepsis, C.difficile infection and viral infections. While we are limited by duration of follow up in our study, these patterns suggest some essential modifiers for inpatient morbidity and mortality, therefore require validation in a large prospective study. Disclosures No relevant conflicts of interest to declare.

7563 Background: There are multiple treatment regimens approved for the management of follicular lymphoma (FL). However, there is limited information available to describe the course of therapy (COT) that patients receive following FL diagnosis. Methods: Using the linked Surveillance, Epidemiology, and End Results (SEER) registry & Medicare claims dataset, we analyzed patients 66 years and older diagnosed with FL from 2000 to 2011. In order to characterize FL treatments, we identified first, second and subsequent-lines of therapy listed in the National Comprehensive Cancer Network guidelines 2.2016. We identified the first COT (COT1) as the first regimen that a patient receives after diagnosis. We identified the second and third COT (COT2 and COT3) as new treatment received following/interrupting COT1 or COT2, respectively. Using visual analytics software, we investigated and reported the proportion of patients receiving each COT, the top three regimens within each COT, and the median time to starting a COT from diagnosis or end of a previous COT. Results: 10,836 FL patients were identified after applying the inclusion/exclusion criteria. Sixty-two percent (N=6,756) of the patients received FL-directed treatment. Among patients receiving COT1, 65% received COT2. Among patients receiving COT2, 79% received COT3. The table below provides additional information on the COT received. Conclusions: Analysis of real-world data indicates that almost 4 out of 10 elderly FL patients do not receive the listed FL-directed treatments. In contrast to rituximab, there was limited use of RCHOP and RCVP after COT1 during the study period. Additional research is needed to understand the differences across demographic groups and associated health outcomes. [Table: see text]

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Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of non-Hodgkin's lymphoma that carries, except for ALK-positive anaplastic large cell lymphoma, a poor prognosis. Only a third of patients live 5years past diagnosis. The incidence of PTCL has been increasing during the last two decades. In recent years, there was a rising interest in PTCL manifested by the abundance of publications dedicated exclusively to this disease. The international T-cell lymphoma project was formed with an aim of unifying efforts towards a better understanding of the diagnosis and management of this disease. Given the poor outcomes of PTCL patients, high-dose chemotherapy and autologous stem-cell transplantation (HDT/ASCT) have been used in the up-front and salvage settings, with different success rates. However, there are no prospective randomized controlled trials addressing the role of HDT/ASCT in a PTCL-restricted population. This article critically reviews the data available from the retrospective and prospective studies addressing this topic. We will emphasize the favorable prognostic factors of HDT/ASCT such as a solid remission at the time of transplantation, a chemotherapy sensitive disease and a low prognostic index score. As novel agents and new therapeutic strategies are introduced, there is a continued need for prospective randomized trials to define the optimal use of HDT/ASCT in managing PTCL.