ALBERT

Description: Background: Prior studies have demonstrated unique clinicopathologic features of the BV of MCL including an inferior response to chemotherapy and poor long-term outcomes as compared to other MCL variants in the pre-rituximab era. A paucity of data precludes whether the use of rituximab or intensified therapy can overcome the inferior outcome associated with the BV. Methods MCL patients (n=169) treated by NLSG between 1983 and 2010 were included. Morphologic variants were classified based on published WHO criteria. We compared disease characteristics, therapy and outcomes according to MCL subtypes using the Kruskal Wallis or Chi-square tests. Univariate probabilities of progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan Meier method. Multivariate analyses were performed using Cox proportional hazards regression to evaluate differences in outcomes of MCL subtypes while adjusting for prognostic covariates. Results The study population included 19% BV, 37% diffuse and 44% nodular subtypes. BV, diffuse and nodular subtypes differed in the median age (61 vs. 68 vs. 59, p=.002) and stage III/IV disease (81% vs. 79% vs. 93%, p=.05) at diagnosis, but did not differ in the distribution of sex, Karnofsky performance status (KPS), MCL international prognostic index (MIPI), lactate dehydrogenase (LDH) level, B-symptoms, or extranodal involvement. Patients received the following therapies: intensified therapy such as Cyclophosphamide, Vincristine, Doxorubicin, and Dexamethasone (Hyper-CVAD) +/- Rituximab (R) (30%), Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-R-like (24%), CHOP-like (35%) or others (11%). Approximately one-third received autologous (25%) or allogeneic (8%) SCT. There was a significant difference in the type of chemotherapy given in each group (p=.002) but not in the use of radiation therapy or proportion in each group receiving autologous/allogeneic stem cell transplant (SCT). Median follow-up across MCL subtypes was similar. Overall response rate was similar for BV, diffuse and nodular subtypes (68% vs. 65% vs. 80%, p=.44). The 5-year progression-free survival for BV vs. diffuse vs. nodular was 16% vs. 22% vs. 31%; p=.06, (Figure 1) and 5-year OS was 24% vs. 32% vs. 56% respectively; p=.005, (Figure 2). In multivariate analysis, compared to BV, diffuse subtype had similar risk of disease progression or death (hazard ratio, HR of 0.78, 95% confidence interval (CI) of 0.48-1.26) whereas nodular subtype had lower risk (HR 0.62, 95% CI 0.39-0.99). Additionally, low or intermediate MIPI, good KPS, absence of B-symptoms and undergoing SCT were associated with lower risk of progression or death. A subset univariate analysis of BV demonstrated no survivors beyond 5 years after conventional chemotherapy, whereas 33% remained alive at 10 years after intensified therapy. Conclusions BV and nodular MCL presented at a somewhat younger median age compared to diffuse MCL, and BV and diffuse MCL was more likely to present as stage I/II disease, compared to nodular MCL. The PFS and OS of BV MCL are similar to diffuse MCL but OS is worse than nodular MCL. The use of SCT may improve survival in MCL including BV variant. Figure 1. PFS of different subtypes of MCL Figure 1. PFS of different subtypes of MCL Figure 2. OS of different subtypes of MCL Figure 2. OS of different subtypes of MCL Disclosures Armitage: Ziopharm Oncology: Consultancy; GlaxoSmithKline: Consultancy; Spectrum Pharmaceuticals: Consultancy; Roche: Consultancy; Tesaro bio Inc: Membership on an entity's Board of Directors or advisory committees.

Description: Introduction: Whether adults aged ≥60 years with AML benefit from multiagent (or intensive) chemotherapy is a matter of controversy. Prior studies have demonstrated conflicting results. We performed analysis of a large National Cancer Data Base (NCDB) to determine the value of multiagent vs. single agent chemotherapy. Methods: NCDB captures approximately 70% of all cancer diagnoses in US, and undergoes rigorous quality monitoring. We utilized NCDB to identify patients aged 60-79 years, who were newly diagnosed with AML (other than APL) between the years 2004-2014. Logistic regression model was used to determine factors associated with the use of multiagent chemotherapy. Kaplan-Meier curves were generated and compared using the log rank test. Logistic regression model and Cox Proportional Hazard model were used for one-month mortality and OS analyses, respectively. In a separate analysis, patients who received single agent (n=6743) vs. multiagent chemotherapy (n=6743) were matched based on the variables age, Charlson comorbidity score, and AML subtypes (good-risk AML, therapy-related AML/AML with myelodysplasia related changes, and other intermediate/high-risk AML). A Cox Proportional Hazard model was used for OS analysis of the matched cohort. Results: Of a total of 25,621 patients, 70% received multiagent chemotherapy. The receipt of multiagent chemotherapy declined with increasing age, Charlson comorbidity score, AML subtypes other than good-risk, female, non-academic center, shorter distance traveled to receive care, lower rate of high school graduation, and more recent year of diagnosis. Patients treated with multiagent chemotherapy had higher likelihood of receiving hematopoietic cell transplant (HCT) (9% vs. 1%); lower one-month mortality (11% vs. 19%); and greater 1-year OS (43% vs. 28%) (Figure 1). The use of multiagent chemotherapy had particularly higher 1-year OS in patients aged 60-64 and 65-69 years, in good-risk AML, patients with Charlson comorbidity score of 0-1 and those who did not receive upfront HCT consolidation (Table 1). One-month mortality (odds ratio 1.64, 95% confidence interval, CI 1.51-1.78) and OS (hazard ratio, HR 1.32, 95% CI 1.28-1.36) remained more favorable for multiagent chemotherapy group in multivariable analyses. Other factors that affected OS included age, comorbidity, AML subtypes, median household income, insurance, use of HCT, academic status of facility, distance traveled to receive care, sex and year of diagnosis. In a matched analysis of 13,486 patients, the use of single agent vs. multiagent chemotherapy resulted in a higher risk of mortality (HR 1.28, 95% CI 1.23-1.32). Conclusions: In one of the largest real-world studies, we demonstrate an association between factors such as age, comorbidity and AML subtypes and the use of multiagent chemotherapy. After adjusting for covariates, the use of multiagent chemotherapy among older adults was associated with higher receipt of HCT, and improved one-month mortality and OS. Improved OS was confirmed in a matched analysis. Certain groups such as patients younger than 70 years, good-risk AML and those with low Charlson comorbidity score had the greater OS benefit with the use of multiagent chemotherapy. Further studies to determine the role of multiagent or intensive chemotherapy are particularly important with approvals of several new drugs in the recent years and integration of many novel drugs in both low-intensity and intensive chemotherapy regimens. Disclosures Bhatt: Tolero Pharmaceuticals: Research Funding; Incyte: Consultancy, Research Funding; Partner therapeutics: Consultancy; Abbvie: Consultancy; Agios: Consultancy; CSL Behring: Consultancy; National Marrow Donor Program: Consultancy; Pfizer: Consultancy. Holstein:Celgene: Consultancy; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy; Genentech: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Sorrento: Consultancy. Al-Kadhimi:Celldex Biotech: Other: Stocks; Seattle Genetics: Other: Stocks. Armitage:Union Pacific: Consultancy; Tesaro bio: Membership on an entity's Board of Directors or advisory committees; Ascentage: Consultancy; Samus Therapeutics: Consultancy; Oncology Analytics: Consultancy; Partner Therapeutics: Consultancy. Gundabolu:Pfizer: Consultancy; Novartis: Consultancy; Jazz pharmaceuticals: Consultancy; Samus Therapeutics: Research Funding.

Description: Abstract 2947 Poster Board II-923 Introduction: DLBCL occasionally presents in leukemic phase, and the prognostic significance of circulating lymphoma cells is unknown. We herein report characteristics and outcomes of newly diagnosed DLBCL presenting in leukemic phase at 2 Institutions. Methods: Flow cytometry database analysis and retrospective chart reviews were carried out with IRB-approval for cases accrued between 2001 and 2008. Leukemic phase DLBCL patients were matched on a 3:1 basis with control DLBCL with no circulating lymphoma cells based on IPI, year of diagnosis, and age ± 10 years. Results: 18 patients, median age 48 years (range 34-80), ECOG PS-1 (22%), 2(38%) and 3(40%), and IPI - 3(56%), 4(40%) and 5(4%) presented in leukemic phase. Extranodal sites included bone marrow (100%), spleen (83%), pleura (61%) and CSF (22%). 61% had B symptoms, and LDH was 6xULN (range, 1-56). WBC was 13,000/microL (range, 7,100-127,400), with 50% lymphoma cells (range, 2-92); these cells were immunophenotypically similar to those in the histologically confirmed DLBCL node, and co-expressed CD19, CD20, CD22, CD38, CD45, HLA-DR and FMC7 in 〉90% of cases, and kappa or lambda light chain restriction in 〉 50%. Karyotype was abnormal and complex in 61%. One patient expired before treatment began. Treatment consisted of R-CHOP (10), R-HCVAD (6), and single agent rituximab (1). 8 (44%) achieved CR (5 R-HCVAD and 3 R-CHOP), 5 (28%) PR, and 4 (22%) had resistant disease. 1 patient was autografted in CR1 and remains in remission. With a median follow-up of 32 months, 2 relapsed in leukemic phase, 1 of whom achieved CR2, but relapsed at the time of conditioning for a consolidative allograft. 10 (56%) patients died from progressive disease, 2 (11%) were lost to follow-up and 6 (33%) remain alive in remission. Overall (Panel A) and progression-free (Panel B) survival curves the 18 leukemic (solid line) and 54 non-leukemic phase (dashed line) DLBCL are depicted in the Figure. Conclusion: DLBCL presenting with circulating lymphoma cells is associated with chemo-resistance (44% CR) and poor outcomes with the exception of those who achieve complete remission. These patients are candidates for alternative therapies. Disclosures: Kaufman: Millenium: Consultancy; Genzyme: Consultancy; Celgene: Consultancy, Research Funding; Merck: Research Funding. Lonial:Millennium: Consultancy, Research Funding; Celgene: Consultancy; BMS: Consultancy; Novartis: Consultancy; Gloucester: Research Funding. Armitage:Eisa: Consultancy; Allo: Consultancy; Ziopharm: Consultancy.

Description: Abstract 288 This is phase I/II trial designed to evaluate the safety and clinical activity of Dasatinib, a potent, broad spectrum inhibitor of 5 critical oncogenic tyrosine kinase families: BCR-ABL, SRC, c-KIT, PDGF receptors (α and β) and ephrin (EPH) receptor kinases, in NHL. The primary end point was maximum tolerable dose (MTD) of dasatinib in the phase I stage and overall response rate (ORR) in phase II stage of the study. Eligible patients must be at least 19 y/o with relapsed or refractory NHL after at least one prior systemic therapy, ECOG performance status 0–2, and able to take oral medications. The Phase I trial utilized a 3+3 design where patients received Dasatinib once daily for 28 day cycles in one of 3 dose cohorts (100, 150, 200 mg daily). Patients continued on Dasatinib until disease progression. NCI grade IV non-hematological toxicity defined dose-limiting toxicity (DLT) in phase I. The phase II stage used a two-stage design. Patients who are in complete or partial remission (CR or PR) after one cycle were considered responders. The study enrolled 27 patients until June 2010. The median age was 58 years (range 34–87). 12 were females and 15 were males. The median number of prior therapies was 4 (range 1–20). The median follow-up period for survivors was 24 months (range 2–30 months). 14 patients were treated in the phase I part of the study and 13 patients were enrolled in phase II so far. 3 patients received 100 mg, 3 patients received 150 mg, and 8 patients received 200 mg daily. The MTD was determined to be 200 mg PO daily. This was later reduced to 150 mg PO daily when a higher incidence of grade 3 pleural effusions was noted (2 of 10 patients receiving 200 mg dose in the first stage of phase II) . 19 patients were evaluable for clinical response after 2 cycles of treatment and are as follows: CR 2, PR 4, SD 8, and PD 5. The ORR was 6/19 (32%). PFS was 17% (with a 95% CI of 5–34%) at 1 year, and 13% (3-29%) at 2 years. Overall survival was 60% (95% CI 38–76%) at 1 year and 50% (95% CI 29–68%) at 2 years. The 2 patients who sustained a CR had peripheral T-cell lymphoma (PTCL). Both patients remained alive, and disease free, for over 2 years since start of treatment. The histological subtypes of the 4 patients who had a PR were: diffuse center follicular lymphoma (2), marginal zone lymphoma (1), and peripheral T-cell lymphoma (1). NCI grade III-IV toxicities noted were hematological (5 thrombocytopenia, 2 anemia, 1 leukopenia, 3 neutropenia), pleural effusion (6), rash (1), diarrhea (2), weakness/orthostasis (1), prolonged QTc interval (1), flash pulmonary edema (1), and skin graft failure (1). In conclusion, Dasatinib shows encouraging activity in heavily pre-treated, recurrent or refractory NHL patients. Toxicity is acceptable and pleural effusions, in addition to cytopenias, were the major toxicities. Dasatinib may be particularly effective in patients with PTCL; possibly because of high expression of PDGFR-α. Phase II of the study is ongoing. Disclosures: No relevant conflicts of interest to declare.

Description: PURPOSE: Rheumatoid arthritis (RA) has been associated with an increased risk of non-Hodgkin’s lymphoma (NHL). We describe the characteristics of NHL patients with antecedent RA. METHODS: Records of the Nebraska Lymphoma Study Group (NLSG) registry between 1982–2004 and the Mayo Clinic lymphoma registry between 1988–1998 were systematically reviewed for RA diagnosis and classified by the quality of supporting evidence. We abstracted available follow-up data through July 1, 2004. Definite cases had either a documented RA diagnosis from a trained rheumatologist or met 4 of 7 American College of Rheumatology criteria. Probable RA cases had a non-rheumatologist diagnosis of RA in addition to one of the following: 1) radiographic joint erosions; 2) disease-modifying anti-rheumatic drug (DMARD) use or; 3) RA-associated deformities (i.e., ulnar drift, swan-neck deformities). Five-year overall survival (OAS), event-free survival (EFS), and rates of treatment response were determined. RESULTS: We identified 74 RA cases (54 definite and 20 probable) with concomitant NHL. These patients had a mean age of 67 + 8 years and were predominantly Caucasian (82%) and female (64%). Of the probable RA cases, a majority had documented DMARD use (n=17). Approximately half of the cases used methotrexate (55%) and were deceased (52%) by the common closing date. The most common NHL subtypes included B-DLCL (n=31), B-FL-1/B-FL-2 (n=12), B-FL-3 (n=6), and B-BL/B-BLL (n=4). Of the remaining 21 cases, most were of B-cell origin (n=13) and included B-EMZL (n=3), B-LPL (n=3), B-UCL (n=2), B-UCL-LG (n=2), B-DFL-2 (n=1), B-MCL (n=1), and B-SLL (n=1). The remaining NHL subtypes included NHL-NOS (n=7) or T-PTCL-LC (n=1). B-symptoms were present for 6 (19%) patients with B-DLCL and none of the patients with B-FL-1/B-FL-2. Complete response rates to NHL treatment were 48% in B-DLCL and 33% in B-FL-1/B-FL-2. For B-DLCL and B-FL-1/B-FL-2, respectively, the five-year OAS was 54% (95% CI 36%–69%) and 65% (95% CI 31%–85%) while the five-year EFS was 48% (95% CI 36%–69%) and 56% (95% CI 24%–79%). For all NHL cases the 5-year OAS was 58% (95% CI 47%–69%) and the 5-year EFS was 49% (95% CI 37%–59%). CONCLUSIONS: Lymphomas developing in the context of RA most often include diffuse large B-cell and follicular subtypes. Complete response rates to standard treatment for these major subtypes ranged from 33 to 48%. For RA patients developing NHL, five-year overall- and event-free survival rates are approximately 50%.

Description: Background: Given the elective nature of hematopoietic stem cell transplantation (HSCT), the increased mortality and the potential loss of decision making capacity, patients undergoing HSCT are encouraged to have advanced care planning (ACP). This however could result in undue anxiety for the patient and their families since going through the process of having ACP explicitly raises the possibility of death. We compared the outcomes of patients with or without ACP who received HSCT for hematologic malignancies. Study Design: Patients age ≥19 yrs undergoing first allogeneic or autologous HSCT for a hematological malignancy between 2001 and 2003 were included in this study. Psychosocial assessments, including discussions about ACP, defined as having living will, power of attorney for health care, and life support instructions, conducted prior to transplant, were reviewed. Patients were classified according to presence or absence of ACP at HSCT. Multivariate Cox regression analysis was used to compare the risk of 100-day mortality between those with and without ACP while controlling for patient-, disease-, and transplant-related variables. Other outcomes evaluated include: days of hospitalization and in-hospital mortality. Results: Of the 380 eligible patients, psychosocial assessments were available for 343 patients (90%). Of these, 146 either had ACP (n=138, 40%) or completed it (n=8, 2%) during the pre-transplant process, while 197 did not have it but were open to the idea of having it in the future (n=161, 47%) or did not plan to have ACP (n=36, 11%). Older patients (p