ALBERT

Description: Purpose: We assessed the survival outcome of patients with anaplastic large cell lymphoma (ALCL) who experienced disease progression or relapse after first line and subsequent therapy. We sought to evaluate the impact of brentuximab vedotin (BV), and survival outcome of patients with ALCL who experienced progression after BV. Patients and Methods: A total of 176 patients (74 ALK+, 102 ALK-) initially diagnosed between 1999 and 2014 were retrospectively analyzed. Progression-free survival (PFS) and overall survival (OS) after the progression/relapse following first-line chemotherapy (PFS1 and OS1), after first salvage therapy (PFS2 and OS2) and after second salvage therapy (PFS3 and OS3) were calculated. Outcome was separately analyzed according to the ALK status focusing on the use of BV. Results: The median age of the patients was 50 (range: 18-89). With a median follow up of 64 months, 111 patients (38 ALK+, 73 ALK-) experienced progression/relapse after the first-line therapy, of which 4 ALK- patients were post upfront stem cell transplant (SCT). Thirty and 15 patients eventually underwent autologous and allogeneic SCT after salvage chemotherapy, respectively. The median PFS1 and OS1 in patients with ALK+ALCL and ALK-ALCL were 8.4 and 28.5 months, and 13.1 and 47.7 months, respectively. In patients with ALK+ALCL, the median PFS1, PFS2 and PFS3 were 53.6, 5.2 and 2.3 months, respectively. The median OS1, OS2 and OS3 were not reached, 47.3 and 6.1 months, respectively. In patients with ALK-ALCL, the median PFS1, PFS2 and PFS3 were 12.9, 3.0 and 2.0 months, respectively. The median OS1, OS2 and OS3 were 54.3, 10.8 and 5.8 months, respectively. Interestingly, there were no significant difference in PFS2 between ALK+ALCL and ALK-ALCL. However, OS2 was significantly longer in patients with ALK+ALCL, suggesting possibly continued chemosensitivity of recurrent ALK+ALCL. A total of 30 patients received BV in 1st salvage (15 patients) and after 2nd salvage (15 patients).The use of BV at 1st salvage was associated with significantly longer PFS2 and OS2 both in patients with ALK-ALCL but not with ALK+ALCL likely due to small number of cases. Mutivariate analysis adjusting baseline PIT risk factors and the duration of the response to first line therapy revealed that use of BV (at any point in the salvage setting) is significantly associated with longer OS2 (HR: 0.43, 95%CI: 0.23-0.80). Overall, 12 patients experienced relapse/progression after BV treatment. The median OS after BV failure was 1.4 months (95%CI: 0.5-9.5 months) (Figure). Summary: Survival outcome for relapsed/refractory patients with ALK+ and ALK- patients is improved with BV. However, survival outcome after BV failure is very poor. A new treatment strategies to consolidate or maintain the response after BV and to develop more safe and better therapeutic options are needed. Figure 1. Figure 1. Disclosures Fanale: Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Research Funding; Infinity: Membership on an entity's Board of Directors or advisory committees; Spectrum: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Research Funding; Genentech: Research Funding; Medimmune: Research Funding; Novartis: Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Molecular Templates: Research Funding; ADC Therapeutics: Research Funding; Onyx: Research Funding; Gilead: Research Funding. Westin:Spectrum: Research Funding. Nastoupil:Celgene: Honoraria; Genentech: Honoraria; AbbVie: Research Funding; Janssen: Research Funding; TG Therapeutics: Research Funding. Wang:Celgene: Research Funding.

Description: Background: The addition of rituximab (R) has improved results for pts with relapsed DLBCL who undergo high-dose chemotherapy followed by ASCT (Khouri, JCO, 2005). Recently, the incorporation of radio-labeled antibodies such as Yttrium 90 (90Y) Ibritumomab Tiuxetan (Zevalin®) to conditioning regimens has been evaluated. Herein, we compare the outcome in pts treated with these 2 regimens. Methods: Pts with relapsed chemosensitive DLBCL were treated on 2 consecutive trials. Between 1999 and 2003, 53 pts were enrolled on a protocol with BEAM combined with R at 1000 mg/m2 and on days +1 and +8 after ASCT (R-BEAM). Between 2004 and 2006, 25 pts were entered onto a trial of Zevalin given at the fixed dose of 0.4 mCi/Kg on day -14 followed by BEAM (days −7 to −1) with R on days +1 and +8 after ASCT (Z-BEAM). Both groups received R during stem cell collection at a dose of 375 mg/m2 the day before chemotherapy for stem cell mobilization and at 1000 mg/m2 7 days later. There was no statistical difference in age, sex distribution, # of prior therapies between the 2 groups. LDH, PET and remission status at transplant were comparable. However, serum b2- microglobulin level was higher in R-BEAM pts [median 2.2 vs 1.9, (p=.02)] and they were also more likely to have an IPI ≥ 1: 39% vs 8% (p=0.005). Results: Median follow-up: 18 mos (range, 6–35) in Z-BEAM and 52 mos (range, 21–74) for R-BEAM. Both groups were staged with CT, PET scan and marrow biopsies, every 3 mos for a year, and then every 6 mos. OS and DFS @ 2 yrs were 92% (95% CI, 72–98) and 84% (95% CI, 62–93) for Z-BEAM vs. 83% (95%CI, 70–91) and 72% (95% CI, 57–82) for R-BEAM (P = 0.5 for both OS/DFS). Within the R-BEAM group, PET status and IPI at transplant were important prognostic factors for OS {91% vs 50% for PET (−) and (+), P = 0.004; 94% vs 67% for IPI 0 vs. ≥1, P = 0.02} and DFS. DFS of pts with IPI 0 were 86% vs 81% for Z-BEAM and R-BEAM, respectively (P = 0.9). A comparison for high IPI pts could not be done due to the small number of such pts in the Z-BEAM group. DFS for pts who were PET (+) were 75% vs 44% within the Z-BEAM and R-BEAM groups, respectively: a difference that did not reach significance due to the small number of pts (4 vs 10). Treatment-related mortality was comparable with only one early death within the Z-BEAM group due to sepsis. Results suggest a faster WBC recovery with Zevalin {ANC 〉 500, day +9 vs. day +11 (p

Description: RAD001 (everolimus, Novartis) is an orally bioavailable derivative of rapamycin with demonstrated anti-proliferative activity against a broad panel of tumor cell lines and antitumor activity in experimental animal models of human cancer. RAD001 inhibits the mammalian target of rapamycin (mTOR) signaling pathway, which is involved in regulating many aspects of cell growth and cell cycle progression. Several lines of evidence implicate the importance of the PI3K/Akt/mTOR pathway in hematological malignancies. As there has been extensive experience with this agent in the solid organ transplantation setting, two dose levels (5 and 10 mg/day) were evaluated in the Phase I portion of this study to determine the maximum tolerated dose (MTD) to be used in the Phase II portion. RAD001 was administered orally once a day at the starting dose level of 5 mg. Fifteen patients have been enrolled, of which 14 (3 B-CLL, 4 MDS, 1 MF, 1 NK/T cell lymphoma/leukemia, 1 MCL, 3 AML, 1 T-PLL) were evaluable for safety and toxicity. Median age was 65 years (range, 56 to 76 years). Twelve patients (86%) had received prior therapy (median, 2 regimens; range, 0 to 6 regimens). Median time on study was 29 days (range, 12 to 105 days). No dose-limiting toxicities were observed in the 6 patients enrolled in the Phase I portion of the study (cohorts of 3 patients per dose level). The most common adverse events were grade ≥ 2 and consisted of hyperglycemia, hyperlipidemia, hypocalcemia, hypomagnesemia, hypophosphatemia and hypokalemia, transaminitis, diarrhea, dermatitis, and mucositis. Grade 3 toxicities consisted of asymptomatic hypophosphatemia (2), and hyperglycemia (3). No patient experienced grade 4 toxicities or death from RAD001. Of the 14 evaluable patients, 2 patients with B-CLL had a 33% and 65% reduction in the size of lymph nodes, respectively, and 1 patient with MDS had decreased transfusion requirements. At the time of analysis, only 1 patient had discontinued therapy due to disease progression. These preliminary findings indicate that RAD001 is well tolerated at a daily dose of 10 mg/day and may have clinical activity in patients with hematologic malignancies. Enrollment is ongoing.

Description: We evaluated the safety and efficacy of NMT vs. AUTO as a treatment modality for patients (pts) with relapsed chemosensitive FL. Pts were considered for AUTO if they did not have a matched sibling donor. Pts were eligible for NMT if they had a donor, especially if pts were 〉 1st relapse or failed a prior AUTO. Between March 1999 and April 2005, 68 consecutive pts were treated. 47 received a NMT after conditioning with fludarabine, cyclophosphamide, HD-R (Blood89:3595, 2001). Twenty-one other pts received AUTO after either Cy/TBI/HD-R (N=8) or BEAM/HD-R (N= 13) (JCO23:2240,2005). The HD-R regimen consisted of 2 injections pre-transplant in NMT or during cell mobilization for AUTO, at 375 mg/m2 and 1000 mg/m2, respectively. Pts then received two additional doses of 1000 mg/m2 at days +1 and +8 post-transplant. Median age of pts (53 yrs), time from diagnosis to transplant (3yrs), % pts in PR (57%) at study entry were equal in both groups. There was no statistically significant difference in gender distribution, histology subtypes of FL grades, history of marrow involvement, beta-2 microglobulin (b2-m), IPI and LDH levels between the two groups. There were however more pts in the NMT group who had 〉 1 relapse (38% vs 19%, P = 0.09), or had 〉 3 lines of therapy (28% vs none). Eight pts (17%) in the NMT group had failed a prior AUTO. Sixty-six pts (97%) had peripheral blood (PB) transplant, two other pts with NMT received marrow from an unrelated donor. With a median follow-up time of 34 months, overall survival rates at 3-year were 88% and 84% for the NMT and AUTO groups, respectively (P=0.8). DFS and risk of progression were comparable between the two groups (85% vs 84%, and 3% vs 5%, respectively). DFS for the 8 pts who received NMT after failing a prior AUTO was 87% at 4-year. Causes of death varied between the AUTO group [Secondary leukemia (2), viral encephalitis (1)] and the NMT group [acute GVHD (2), chronic GVHD (2), unknown (1)]. We compared the outcome of AUTO in this study [AUTO Study Group), to a historical group [AUTO Control Group] of pts who received an AUTO under an immediately preceding protocol (years of therapy: 1994-1998). Pts in the AUTO Control Group were younger [Median age was 47 vs. 53 yrs, respectively, P = 0.007)], received Cy/VP-16/TBI without HD-R as conditioning regimen, and mostly (84% of pts) received in-vitro purged marrow as the source of graft (P 〈 0.001). Other disease characteristics were not statistically different between them. Results at 3-years demonstrated a higher risk of progression in the AUTO Control Group compared to the AUTO Study Group (26% vs. 5%, respectively, P = 0.09), an inferior DFS (58% vs. 84%, respectively, P = 0.04), and a tendency for a shorter survival (74% vs 84%, respectively, P = 0.2). These data suggest that NMT has a spectrum of safety that becoming comparable to AUTO. HD-R appears to improve the outcome after AUTO. Longer follow-up is needed to assess remission duration in the 2 study groups. A prospective controlled trial of AUTO vs. NMT using HD-R in each arm is warranted to assess the optimal strategy for treatment of relapsed FL.

Description: Introduction CAR-T cells targeting CD19 positive B-cells have improved outcomes and remission rates in relapsed/refractory non-Hodgkin lymphoma (NHL) and B-cell acute lymphoblastic leukemia (B-ALL). Although toxicities contributing to non-progression related mortality (NRM) have been reported in the pivotal trials, its incidence in the standard of care setting post-approval is unknown. The following data includes toxicity profiles implicated in events leading to NRM obtained from the FDA adverse event reporting system (FAERS) with comparison to MD Anderson (MDACC-L) CAR-T Lymphoma cohort and to the pivotal CAR-T trials. Methods We retrospectively queried FAERS for all adverse events (AE) associated with tisagenlecleucel (T) and axicabtagene ciloleucel (AC) reported from January 1, 2013-June 30, 2019. FAERS contains AEs from clinical trials and healthcare providers and is standardized according to the Medical Dictionary for Regulatory Activities (MedDRA), a clinically validated AE classification dictionary for pharmacovigilance monitoring. All cases with the outcome of death as reported by FAERS were queried. Cases in which the time to event with NRM was greater than 30 days or unknown were excluded. Total events recorded with NRM and disease progression were categorized according to the MedDRA coding system and compared using the chi-squared and a two-sided Fisher's exact test (statistical significance: p

Description: Introduction: Mantle cell lymphoma (MCL) is a rare and incurable subtype of B-cell lymphoma. Intense chemo-immunotherapy with 8 cycles of Rituximab-HyperCVAD alternating with Rituximab-Methotrexate-Ara C is associated with an overall survival of 10.7 years but the 10-year cumulative incidence of therapy-related myeloid neoplasm was 6.2%. The ibrutinib-rituximab combination has produced durable responses in 88% of patients with relapsed and refractory MCL with acceptable toxicity. This gives rise to a "Window" of opportunity to use chemotherapy-free induction with ibrutinib plus rituximab followed by fewer cycles of chemo-immunotherapy consolidation in young and fit patients with newly-diagnosed, untreated MCL. Methods: Enrolment began in June 2015 for a Phase II single-center clinical trial consisting of an initial chemotherapy-free phase (window) of ibrutinib and rituximab combination treatment in Part 1 until best response, followed by a shortened course of intense chemo-immunotherapy in Part 2 among young newly diagnosed MCL patients of ≤65 years. The primary objective was to evaluate the response rate of ibrutinib plus rituximab. The secondary objectives were to evaluate the progression free survival (PFS) of ibrutinib plus rituximab after consolidation with a shortened number of cycles of intense chemo-immunotherapy, and to further evaluate the toxicity profile. Ibrutinib is dosed at 560 mg orally, daily, continuously. Rituximab is dosed at 375 mg/m2 IV weekly x 4 during cycle 1 (28 days cycle), then day 1 of cycles 3-12. Intense chemo-immunotherapy consists of rituximab plus cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD); alternating every 28 days with rituximab plus high-dose methotrexate-Ara C. If in complete remission (CR) after initial ibrutinib and rituximab treatment, a total of 4 additional treatments of intense chemo-immunotherapy are given. If the patient is in partial response or progression, and if responding to intensive chemo-immunotherapy, a total of 2 cycles of chemo-immunotherapy therapy are administered beyond achievement of CR. Results: As of August 2, 2016, we have completed the target enrolment by accruing 50 out 50 patients with newly-diagnosed untreated MCL. Forty one (n=41) patients have begun treatment and 36 are evaluable for response. Of the 36 evaluable patients, overall response rate (ORR) to Part 1 alone (Ibrutinib plus rituximab) is 100% (n=36) with PR in 28% (n=10) and CR in 72% (n=20). Nineteen 19 patients have completed both Part 1 (ibrutinib and rituximab) and Part 2 (chemo-immunotherapy). The ORR to both Part 1 and Part 2 (n=19) was 100% and was equal to the CR rate (100%, n=19), i.e. all have achieved a CR to Part 1 and Part 2. Toxicities are recorded as the number of patients experiencing a certain adverse event. Regardless of their relation to study drug in Part 1, the most common grade 1-2 non-haematological (non-heme) adverse effects (AEs) are fatigue (n=40), diarrhea (n=25), rash (n=24), myalgia (n=22), oral mucositis (n=17), peripheral neuropathy (n=15), nausea (n=14), blurred vision (n=14), edema (n=13), constipation (n=12), headache (n=11), dry eyes (n=9), dizziness (n=9) and watery eyes (n=6). Grade 3 non-heme AEs included fatigue (n=3), nausea (n=0), rash (n=1), pleural effusion (n=1), infection (n=2) and dyspnea (n=1). There was no grade 4 or grade 5 non-heme toxicities in Part 1. In part 2, common grade 1-2 hematological (heme) AEs was anemia (n=13). Grade 3-4 haematological AEs included neutropenia (n=2), ALT increase (n=1) and febrile neutropenia (n=1). In Part 2, there was no grade 5 hematologic toxicity. The toxicity after intensive immune-chemotherapy in shortened cycles are much improved compared to historical controls but longer follow-up is needed. Conclusions: Preliminary data indicate that the chemotherapy-free induction with ibrutinib and rituximab in newly diagnosed, young MCL patients was efficacious and well-tolerated. This unprecedented efficacy and safety may provide a window of opportunity for less chemo-immunotherapy needed for consolidation. Table Preliminary findings form the Window Study: a phase II clinical trial Table. Preliminary findings form the Window Study: a phase II clinical trial Disclosures Wang: Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Onyx: Research Funding; BeiGene: Research Funding; Pharmacyclics: Research Funding; Kite Pharma: Research Funding; Asana BioSciences: Research Funding; Juno Therapeutics: Research Funding; Acerta Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding. Fayad:Seattle Genetics: Consultancy, Research Funding.

Description: Background: Patients with advanced indolent non-Hodgkin lymphoma (iNHL) can develop chemoresistance and most relapse following standard therapy. Lenalidomide activates NK cells ± T cells and leads to in vivo expansion of immune effector cells in NHL models. In preclinical studies, we have shown the synergistic anti-tumor effect of combining lenalidomide with anti-CD20 molecules. (Wang 2007) The combination of rituximab and lenalidomide (R2) in relapsed and untreated iNHL is highly active. (Fowler 2014) We hypothesize these responses are related to augmentation of immune response and ADCC through alteration of immune cell subsets in tumor and peripheral blood. Obinutuzumab is a glycosylated type II anti-CD20 molecule with enhanced affinity for the FcγRIIIa receptors leading to improved ADCC. The primary objective of this study was to determine the safety and maximum tolerated dose of lenalidomide and obinutuzumab in patients with relapsed/refractory iNHL. Methods: Patients with relapsed SLL, marginal zone, and follicular lymphoma (gr 1-3a) were eligible. Patients enrolled in three predefined dose cohorts of lenalidomide (10mg,15mg, 20mg) given on days 2-22 of a 28 day cycle. Obinutuzumab was given at a fixed dose (1000mg) IV on days 1,8,15 and 22 of cycle 1 and day 1 of subsequent cycles. All patients received prophylactic steroids prior to obinutuzumab. In the absence of toxicity or progression, the combination was continued for up to 12 cycles. The standard '3+3' design was used with dose limiting toxicities (DLT) assessed during cycle 1. Patients attaining ≥partial response continued obinutuzumab every 2 months for up to 24 months. Prophylactic growth factors were not used. Adverse events were graded using CTCAE version 4.03. Results: 15 patients ( 9 during dose escalation, 6 during dose expansion at target dose) were enrolled; all were evaluated for safety and efficacy (all having had at least 1 post-baseline response assessment). The median age was 60 (36-82) years, and 7 (47%) were male. 21% of patients with follicular lymphoma had low, 29% intermediate, and 50% high FLIPI scores at study entry, 1 patient had SLL. No DLTs were observed during dose escalation. The most common grade 1-2 non-hematologic toxicities were fatigue 12/15 (80%), constipation 9/15 (60%), diarrhea 7/15 (47%), dyspnea 7/15 (47%), and myalgia 7/15 (47%). Grade ≥ 3 events included neutropenia (n=3, 20%), infection (n=2, 13%),thrombocytopenia (n=1, 6%), and two infusion related reactions (13%), both occurring during the first infusion of obinutuzumab. With a median follow up of 8.2 (4.1-14 mo), the overall response rate was 93% with 27% (4/15) achieving a complete response and 67% (10/15) with a partial response, all responding patients remain on active therapy. One patient progressed after 8 months and was withdrawn from study. Conclusion: The combination of 20 mg of lenalidomide and 1000mg obinatuzumab is safe and effective in patients with relapsed iNHL. Adverse events appeared similar to our prior experience with lenalidomide and rituximab. Overall response rates were high, with complete responses increasing with prolonged duration of therapy. Correlative efforts are ongoing to study the immunomodulatory potential of the combination and to identify biomarkers of response. The phase II portion of this study is currently enrolling with dose expansions in relapsed iNHL. Disclosures Off Label Use: Lenalidomide off label in low grade lymphoma Obinutuzumab off label in low grade lymphoma. Fanale:Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Research Funding; Infinity: Membership on an entity's Board of Directors or advisory committees; Spectrum: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Research Funding; Genentech: Research Funding; Medimmune: Research Funding; Novartis: Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Molecular Templates: Research Funding; ADC Therapeutics: Research Funding; Onyx: Research Funding; Gilead: Research Funding. Nastoupil:Celgene: Honoraria; Janssen: Research Funding; AbbVie: Research Funding; TG Therapeutics: Research Funding; Genentech: Honoraria.

Description: Background MCL is incurable. Bortezomib has shown single agent activity of 33% in relapsed MCL. Pre-clinical published data shows additive/synergistic activity of BCR. Materials and methods   MCL pts  ages 18 through 85, with adequate organ function unless due to lymphoma, and without HIV-1 infection or any significant medical/mental condition, were treated under an IRB-approved study, consisting of Bortezomib  1.3 mg/m2 IV given on days 1, 4, 8, and 11 (dose on day 11 omitted early on study); fractionated cyclophosphamide 300 mg/m2 q 12 hrs days 1, 2, and 3, and rituximab 375 mg/m2 day 1. Cycles were repeated every 21 days for a total of 6 or less if a response was achieved and patient qualified for SCT. Results From  9/2009 to 8/2012, twenty-one patients were entered in the study. Their clinical characteristics are as follows: Overall response (OR)/CR rates:  71%/53%. One patient had stable disease and 4 patients progressed. With a Median follow-up of 31 months, the median TTP was 15.8 months and the median OS was 36.4 months. Toxicity was mainly hematologic. With 77 cycles given, grade 3 anemia was 5%, grade 3 / 4 neutropenia was 16%/9%, and grade 3 / 4 thrombocytopenia was 19%/8%. Early in the study, day 11 dose of bortezomib was omitted because of low counts by day 11 of cycle. Non-hematologic toxicity included grade 3 neutropenic fever (1%), and grade 3 fatigue (3%). No patient developed sensory neuropathy grade ¾. Conclusion Bortezomib can be safely combined with cyclophosphamide and rituximab and results in high rates of overall/complete responses in patients with relapsed/refractory MCL. Disclosures: Off Label Use: Gemcitabine, fludarabine and melphalan for transplant conditioning. Younes:Seattle Genetics, Inc.: Advisory/Scientific Board Membership Other, Honoraria, Research Funding. Pro:Seattle Genetics, Inc.: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Travel expenses Other.

Description: Background: Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma. As the incidence of DLBCL increases with age, the number of elderly patients with DLBCL in our aging society continues to increase. However, patients aged ≥ 80 years old are often frail and carry multiple comorbidities, and are generally underrepresented in prospective clinical trials. Patients and Methods: 207 patients, age ≥80 years of age at diagnosis of de novo DLBCL were identified between 2002 and 2014 at MD Anderson Cancer Center and included in this retrospective analysis. Failure-free survival (FFS) and overall survival (OS) were examined; baseline characteristics and frontline therapy were evaluated for the association with survival outcomes by hazard ratio (HR). Results: Median age was 83 years (range 80-96). Fifty-five percent of the patients were male, 66% had advanced stage and 37% had poor performance status (ECOG PS≥2). Forty-five percent of the patients were IPI high-intermediate or high risk. Eighty patients (39%) were GCB and 49 patients (24%) were non-GCB subtype, respectively, according to the Hans criteria, with 78 patients lacking data for classification. Thirty-two patients (15%) had ≥4 scores by Charlson comorbidity index (CCI, Charlson 1987). Treatment received included R-CHOP (n=144, 70%), R-EPOCH (n=12, 6%), and non-anthracycline based therapies including R-CEOP and R-CVP (n=20, 10%). Sixteen patients (8%) did not receive any treatment due to deteriorated condition or patient's decision. Fifteen patients received other treatment such as radiation and rituximab monotherapy. With a median follow up of 38.1 months, 88 patients (43%) experienced progression/relapse and 123 patients (59%) died. Sixty-two patients (50%) died of lymphoma, 32 patients (26%) died of other co-morbid conditions while in remission and 17 patients (14%) died as a result of treatment complication during frontline therapy. Thirteen patients died during R-CHOP, 2 patients each died during R-CEOP or R-CVP and R-EPOCH, respectively, most were the result of infection or multi-organ failure. The 3-year FFS and OS were 55% and 54%, respectively. After 3-years, almost all deaths were attributed to other diseases (Figure A). Patients who received R-CHOP or R-EPOCH had a significantly longer FFS than patients who received R-CEOP or R-CVP (Figure B). CCI ≥4 was not associated with inferior FFS but was significantly associated with inferior OS. Multivariate analysis for OS adjusted by IPI and frontline treatment revealed that being female was associated with significantly longer OS (HR: 0.50, 95% CI, 0.33-0.75, p2.0mg/l had significantly inferior OS (HR: 7.21, 95% CI, 1.67-31.1, p=0.01). Conclusion: Patients with DLBCL aged ≥80 years who received anthracycline-based regimens such as R-CHOP or R-EPOCH had outcomes similar to younger patients with de novo DLBCL. Although they carry higher risks of therapy-related mortality, anthracycline-based regimens are moderately well tolerated, and their use should not be minimized based solely on age. Inclusion of very elderly patients in prospective clinical trials is warranted to identify the most effective management strategy for this population. Figure 1. Figure 1. Disclosures Westin: Spectrum: Research Funding. Fanale:Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Research Funding; Infinity: Membership on an entity's Board of Directors or advisory committees; Spectrum: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Research Funding; Genentech: Research Funding; Medimmune: Research Funding; Novartis: Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Molecular Templates: Research Funding; ADC Therapeutics: Research Funding; Onyx: Research Funding; Gilead: Research Funding. Rodriguez:Orthobiotech: Research Funding. Wang:Celgene: Research Funding. Nastoupil:AbbVie: Research Funding; TG Therapeutics: Research Funding; Genentech: Honoraria; Celgene: Honoraria; Janssen: Research Funding.

Description: Background: CNS relapse is a rare but fatal complication of patients with peripheral T-cell lymphoma (PTCL). Several large studies have identified risk factors for CNS relapse in PTCL, such as elevated serum lactate dehydrogenase (LDH), 〉1 extranodal sites of involvement and high International Prognostic Index (IPI) score. We performed an analysis of histologic type of PTCL to identify additional risk factors for CNS relapse. Patients and Methods: A total of 616 patients with PTCL diagnosed between 1999 and 2014 were analyzed retrospectively including: 174 not otherwise specified (NOS), 144 angoimmunoblastic T-cell lymphoma (AITL), 76 ALK+ anaplastic large cell lymphoma (ALCL), 103 ALK-ALCL, 55 nasal type T/NK cell lymphoma (NK/T), 23 hepatopslenic T-cell lymphoma (HSTL), 16 enteropathy-type T-cell lymphoma (EATL), 13 adult T-cell leukemia/lymphoma (ATLL), and 12 subcutaneous panniculitis-like T-cell lymphoma (SPTL). Patients with CNS involvement at diagnosis (n=15) were excluded from this study. Progression-free survival (PFS) and overall survival (OS) were calculated and pretreatment characteristics were evaluated for association with survival outcomes by hazard ratio (HR). Cumulative incidence of CNS relapse was calculated by competing risk (death without CNS relapse) regression analysis. Results: The median age of the patients was 56 years (range, 17-93 years). With a median follow up of 57 months, 15 patients (4 PTCL-NOS, 1 AITL, 4 ALK+ALCL, 2 ALK-ALCL, 2 NK/T, and 2 ATLL) experienced CNS relapse, and 321 patients (52%) died without having had CNS relapse. One-year and 5-year cumulative incidence of CNS relapse were 1.8% (95%CI: 1.0-3.1%), 2.4% (95%CI: 1.3-3.8%), respectively. The 5-year cumulative incidence of CNS relapse was 1.8% in PTCL-NOS, 0.7% in AITL, 5.3% in ALK+ALCL, 2.1% in ALK-ALCL and 3.6% in NK/T (Figure). All patients with CNS relapse eventually died, with median OS duration from CNS relapse of 1.6 months. Extranodal sites of involvement 〉1 (HR: 6.0, 95%CI: 2.0-17.4) and higher IPI score (HR: 1.8, 95%CI: 1.1-3.1, by one increase in IPI score) were risk factors of CNS relapse by univariate analysis. ALK+ALCL patients who had 〉 1 extranodal site of involvement (N=19) had very high risk of CNS relapse with one year cumulative incidence of 15% (95%CI: 3.7%-33.5%), with all occurring within six months after diagnosis. Summary: CNS relapse in patients with PTCL is rare as reported previously. However, the risk varies by histologic type. Specifically ALK+ALCL patients with 〉 1 extranodal site of involvement have a very high risk of CNS relapse in early phase of treatment, and CNS evaluation at the time of diagnosis and possibly CNS targeted prophylaxis may be appropriate. Figure Figure. Disclosures Westin: ProNAi: Membership on an entity's Board of Directors or advisory committees; Chugai: Membership on an entity's Board of Directors or advisory committees; Spectrum: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Fayad:Seattle Genetics: Consultancy, Research Funding. Wang:BeiGene: Research Funding; Kite Pharma: Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Asana BioSciences: Research Funding; Dava Oncology: Honoraria; Asana biosciences, Beigene, Celgene, Juno, Kite, Onyx, Pharmacyclics: Research Funding; Acerta: Consultancy, Research Funding; Juno Therapeutics: Research Funding. Fowler:Roche: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Jannsen: Consultancy, Research Funding; Gilead: Research Funding; Infinity: Consultancy, Research Funding; TG Therapeutics: Consultancy. Oki:Novartis: Research Funding.