ALBERT

Description: Abstract 1689 Poster Board I-715 Introduction The use of the proteasome inhibitor bortezomib has demonstrated activity in multiple myeloma and lymphomas. The HDAC inhibitor romidepsin is being evaluated in CTCL and PTCL, though its activity in B-cell lymphomas is less clear. We hypothesized that the combination of bortezomib and romidepsin would result in synergistic apoptosis in different B-cell NHL cell lines based upon the observed activity of this combination in more mature B-cell malignancies such as myeloma. Experimental Design Daudi, HT, Ramos and SUDHL-4 cell lines were exposed to different concentrations of bortezomib and romidepsin, separately, concurrently, and sequentially. Cell viability was assessed using MTT-assay, induced apoptosis was evaluated using Annexin V and PI staining from 24-48 hours. Apoptosis was also evaluated using western blot analysis of caspases and PARP cleavage. LC3 and HDAC6 level expressions were performed to determine if the effect of the combination was a result of the aggresome or autophagy pathway. Cell cycle studies were also performed to study if there were any changes after treating cells with the combination. Results The combination of bortezomib and romidepsin resulted in synergistic B-cell apoptosis as measured by MTT-assay with combination indices of 〈 0.5. This was associated with increased caspases and PARP cleavage as early as 24 hours after exposure. Order of addition experiments demonstrated definite sequence specificity. When romidepsin was added first, and 6 hours later followed by bortezomib, apoptosis was enhanced, compared to both agents being given concurrently or when bortezomib was administered first. Cell cycle analysis studies demonstrated that pretreatment of cells with romidepsin for 6 hours followed by the addition of bortezomib arrested the cells in G2M phase. HDAC6 expression was significantly reduced following combination therapy, and LC3-I was cleaved to LC3-II in treated cells suggesting that the combination affected aggresome formation and autophagy. Conclusion The combination of romidepsin and bortezomib at low nanomolar concentrations suggests that this may be an important clinical combination to test in patients with relapsed or refractory B-cell malignancies. Sequence of administration data is currently being tested to determine if the effect is a result of autophagy inhibition as is seen in myeloma cell lines. Additional mechanistic studies will be presented with the goals of identifying predictors of response that can then be validated in prospective clinical trials. Disclosures Lechowicz: Gloucester: Consultancy. Kaufman:Millennium: Consultancy; Genzyme: Consultancy; Celgene: Consultancy; Merck: Research Funding; Celgene: Research Funding. Lonial:Gloucester: Research Funding; Novartis: Consultancy; BMS: Consultancy; Millennium: Consultancy, Research Funding; Celgene: Consultancy. Flowers:Millennium: Research Funding.

Description: Introduction: Tenalisib (RP6530) is a novel, highly specific, dual PI3K δ/γ inhibitor with nano-molar inhibitory potency at the enzyme and cellular level. PI3K plays a critical role in T-cell development and activation and several studies have validated the PI3K-AKT pathway as a potential therapeutic target in T cell lymphomas. Preliminary results of the ongoing Phase 1/1b T-cell lymphoma (TCL) study demonstrated an acceptable safety profile with encouraging clinical activity in relapsed/refractory TCL (Oki, ASCO 2018 and Iyer, ASH 2018). We now present the final results of the study (NCT02567656). Methods: This study comprised of four-dose escalation cohorts, followed by two dose expansion cohorts at MTD enrolling 20 patients each in PTCL and CTCL cohorts. Patients had histologically confirmed TCL, ECOG PS ≤2, and had received ≥1 prior therapy. Patients received Tenalisib [200 mg BID-800 mg BID (fasting), 800 mg (fed only)] orally until progression or unacceptable toxicity. The primary objectives were to determine the MTD and pharmacokinetic profile. The secondary objective was to evaluate overall response rate (ORR) and duration of response. Responses were evaluated for PTCL and CTCL based on IWG criteria (Cheson 2007) and mSWAT respectively. Adverse events were graded according to CTCAE v4.03. Results: Fifty-eight patients were enrolled in study, 19 in dose escalation and 39 in dose expansion (28 PTCL and 30 CTCL). Median number of prior therapies was 4 (range, 1-15). Safety assessment of 58 patients receiving at least one dose of Tenalisib demonstrated an acceptable safety profile. Treatment related Grade≥3 AEs were elevated ALT/AST (21%), rash (5%), and hypophosphatemia (3%). These events were reversible and managed by withholding study drug. Additionally, in few patients (N=9), steroids were used to manage elevated ALT/AST. There were six treatment related serious adverse events, none of these led to fatal outcome. At end of the study, four (3 CTCL; 1 PTCL) patients who completed minimum 8 cycles of therapy were rolled over to a compassionate use study (NCT03711604) and were followed up. Efficacy assessments demonstrated an ORR of 46% (3 CR and 13 PR) and clinical benefit rate (CR+PR+SD) of 77%. Subset efficacy analysis showed an ORR in PTCL of 47% (3 CR; 4 PR) and in CTCL of 45% (9 PR). The median time to initial response was 1.8 months and was similar in both sub-types. The overall median DOR was 4.91 months (range 0.9-26.6); in PTCL patients the DOR was 6.53 months, (range: 0.97-21.0) and 3.8 months (range: 1.67-25.67) in CTCL patients. In 3 PTCL patients who achieved CR, the median DOR was 19.5 months (range 7.5-21). Conclusion: Tenalisib demonstrated promising clinical activity and an improved safety profile in patients with relapsed/ refractory TCL. Currently, a phase I/II combination study to further evaluate safety and efficacy with romidepsin is ongoing in this target population. Disclosures Iyer: Arog: Research Funding; Bristol-Myers Squibb: Research Funding; Novartis: Research Funding; Seattle Genetics, Inc.: Research Funding; Genentech/Roche: Research Funding; Incyte: Research Funding. Zain:Spectrum: Consultancy; Seattle Genetics: Consultancy. Korman:Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Glaxo: Honoraria, Membership on an entity's Board of Directors or advisory committees; Immune Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kyowa: Research Funding; Leo: Research Funding; Menlo: Research Funding; Merck: Research Funding; Novartis: Consultancy, Honoraria, Speakers Bureau; Pfizer: Research Funding; Principia: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Prothena: Research Funding; Regeneron: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Rhizen: Research Funding; Sun: Honoraria, Membership on an entity's Board of Directors or advisory committees; Syntimmune: Research Funding; UCB: Research Funding; Valeant: Honoraria, Membership on an entity's Board of Directors or advisory committees; Eli Lilly: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Dermira: Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Research Funding; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Routhu:Rhizen Pharmaceuticals S.A.: Employment. Barde:Rhizen Pharmaceuticals S.A.: Employment. Nair:Rhizen Pharmaceuticals S.A.: Employment. Huen:Galderma Inc: Research Funding; Glaxo Smith Kline Inc: Research Funding; Rhizen Pharmaceuticals: Research Funding; Innate Pharmaceuticals: Research Funding.

Description: Abstract 364 Patients (pts) with advanced stage CTCL have a poor prognosis with standard therapy whereas AHCT possibly is curative. Published experience with AHCT for CTCL is modest. We report the outcomes of a large cohort of CTCL pts receiving AHCT (N=133) reported to the CIBMTR from 2000–2009. The majority of pts 129 (97%) were diagnosed with Mycosis Fungoides or Sezary Syndrome. Only 8 (6%) received AHCT in a complete remission (CR) while 46 pts (35%) never achieved CR pre-AHCT. Most pts (83%) were transplanted beyond 12 months from diagnosis. Median (range) time from diagnosis to transplant is 29 (4-206) months. Peripheral blood was the main graft source (83% vs. 14% marrow and 3% cord blood). Donor types included: 66 HLA-identical siblings (50%), 56 unrelated donors (42%), 11 from other related donors (8%). Reduced intensity conditioning (RIC) was used in 64%. Recipients of RIC were on average older (median age 51 vs. 44 yr for myeloablative) and transplanted in later study years. Among the myeloablative regimens, cyclophosphamide with total body irradiation was the most common (38%) whereas among RIC, fludarabine in combination with busulfan, cyclophosphamide or melphalan was used in 50%. GVHD prophylaxis regimens varied. Overall mortality at 30 and 100 days was 7% and 16%, respectively. Overall survival at 6 mo and 2 yr was 75% (95% CI 67–82%) and 44% (95% CI 34–53%), respectively. Conditioning intensity was not different statistically for the overall survival of these pts (figure 1). Treatment related mortality (TRM) at 6 mo and 2 yr was 10% (95% CI 5–17%). Progression/relapse of CTCL was 44% (95% CI 34–54%) at 6 mo and 58% (95% CI 47–68%) at 2 yr. Progression free survival at 6 mo was 46% (95% CI 36–57%) and at 2 yr 32% (95% CI 23–42%). The incidence of grade II-IV acute GVHD was 36% (95% CI 22–50%) and of chronic GVHD 31% (95% CI 19–45%) in a subset of reported pts. Infection as a cause of death does not seem to be increased in CTCL transplanted pts. Conditioning intensity did not impact TRM or the risk of progression. This very large series of allogeneic HCT demonstrates feasibility in pts with advanced CTCL with a low TRM and long term progression free survival in approximately one third of pts. Progressive disease was the primary cause of treatment failure in this cohort of pts with advanced disease. Figure 1. Figure 1. Disclosures: No relevant conflicts of interest to declare.

Description: Background: Bortezomib-containing combination chemotherapy regimens are effective in non-Hodgkin's lymphoma (NHL), although there are limited data on toxicity in the front-line setting for indolent NHL when combined with reduced-dose vincristine-containing chemotherapy. Our group (Sinha et al, Cancer 2012) reported outcomes from a phase I study of bortezomib combined with rituximab, cyclophosphamide, doxorubicin, modified vincristine, and prednisone (VR-CHOP) and found a maximum tolerated dose (MTD) of bortezomib (V) of 1.6mg/m2 with vincristine capped at 1.5 mg with an overall response rate (ORR) of 100%. Herein we report the results of our phase II study of this regimen. Patients and Methods: Eligible patients had untreated indolent NHL (small lymphocytic lymphoma [SLL], marginal zone lymphoma [MZL], or follicular lymphoma [FL] grades 1-3) meeting standard criteria for treatment or with FL international prognostic index (FLIPI) ≥3. Patients received V administered at a dose of 1.6mg/m2 on days 1 and 8 as well as rituximab (R) 375mg/m2, cyclophosphamide 750mg/m2, doxorubicin 50mg/m2, and vincristine 1.4mg/m2 (capped at 1.5mg/dose) on day 1 and prednisone 100mg on days 1-5 of a 21-day cycle. Patients received at least 6 cycles and up to 8 cycles of therapy at the discretion of the treating physician. Patients who achieved a complete response (CR) after induction were assigned to receive maintenance R 375mg/m2 every 12 weeks for 2 years while patients with a partial response (PR) or stable disease received R 375mg/m2 along with V 1.6mg/m2 (VR), both administered weekly for 4 weeks every 6 months for up to 2 years. Response was assessed by Cheson 1999 criteria, and toxicity assessed by CTCAE version 3.0. One FL patient discontinued study therapy after cycle 2 when a central pathology review revised the diagnosis to diffuse large B-cell lymphoma. This patient was not included in the efficacy analysis but is included in the safety reports. CR rate and ORR were determined at the conclusion of induction therapy, and progression-free survival (PFS) and overall survival (OS) were evaluated by the Kaplan-Meier method from the date of study entry. Results: Thirty patients received at least 1 treatment of VR-CHOP, including 16 males and 14 females. The median age was 58 (range: 31-71), and histologies included MZL (n=5), SLL (n=4), and FL (Grade 1, n=7; Grade 2, n=12; Grade 3, n=2). FLIPI score for patients with FL were 1 (n=2), 2 (n=4), 3 (n=12), and 4 (n=3). Twenty-nine were evaluable for response, including 19 patients with CR and 10 patients with PR at the conclusion of induction therapy (CR rate of 66%; ORR of 100%). For 20 evaluable patients with FL, the CR rate was 75%. Twenty-five patients proceeded with maintenance therapy, including 6 patients who received VR and 19 patients who received R alone. Three patients with PR to induction converted to CR after maintenance with VR. Four patients received no maintenance due to refusal/lost to follow-up (n=2), toxicity (n=1), and progression (n=1). Three patients with PR received only R due to neuropathy. Four patients have relapsed or progressed on therapy, including 1 patient prior to starting maintenance, 2 patients during VR maintenance, and 1 patient who achieved a PR but was receiving R maintenance. One additional patient progressed after completing R maintenance. With a median follow-up of 39 months, 3-year PFS rate is 85.8%, and the 3-year OS rate is 96.4% (Figure). Grade ≥3 peripheral neuropathy was noted in 2 patients (7%), while grade 1-2 neuropathy occurred in 17 patients (57%). Grade 3-4 hematologic toxicities included neutropenia (n=14, 47%), thrombocytopenia (n=3, 10%), anemia (n=1, 3%), and febrile neutropenia (n=1, 3%). Eight patients experienced additional grade 3 non-hematologic toxicities, including the following which occurred in more than 1 patient: vomiting (n=3, 10%), abdominal pain (n=2, 7%), fatigue (n=2, 7%), hyperglycemia (n=2, 7%), hypokalemia (n=2, 7%), and nausea (n=2, 7%). Conclusion: VR-CHOP is highly efficacious in the front-line setting for management of patients with untreated indolent NHL, and toxicities are expected and manageable. Incidence of grade 3 peripheral neuropathy is low with incorporation of a decreased dose of vincristine, and the PFS compares favorably with previously reported outcomes in FL and indolent NHL for R-CHOP, R-Bendamustine, and R-CHOP plus maintenance R. Figure 1 Figure 1. Disclosures Cohen: Janssen: Research Funding; BMS: Research Funding; Seattle Genetics: Consultancy; Pharmacyclics: Consultancy. Off Label Use: Bortezomib is not currently approved for follicular lymphoma, marginal zone lymphoma, or small lymphocytic lymphoma and is being evaluated in combination with a standard induction regimen.. Kaufman:Millennium: Consultancy; Janssen: Consultancy. Nastoupil:TG Therapeutics: Research Funding; Celgene: Honoraria; Genentech: Honoraria; Janssen: Research Funding. Lechowicz:Millennium: Consultancy. Lonial:Millennium, Celgene, Novartis, BMS, Onyx: Consultancy, Research Funding. Flowers:Gilead, Spectrum, Millennium, Janssen: Research Funding; Celgene, Prescription Solutions, Seattle Genetics, Millennium (unpaid), Genentech (unpaid) : Consultancy.

Description: Introduction: MAVORIC was an open-label, multicenter, randomized phase 3 study evaluating the safety and efficacy of mogamulizumab (moga) compared to vorinostat (vori) in patients with mycosis fungoides (MF) or Sézary syndrome (SS) who had failed at least one prior course of systemic therapy (NCT01728805). Primary results have been reported (Kim et al. Lancet Oncol 2018) and were based on a data cutoff date of December 31, 2016. The primary endpoint was progression-free survival (PFS); patients in the moga treatment arm experienced significantly longer PFS compared to patients in the vori treatment arm (median 7.7 months vs 3.1 months; p

Description: Abstract 2686 Background: DLBCL is the most commonly occurring form of non-Hodgkin lymphoma and is a highly curable disease, but one that is universally fatal if untreated or improperly treated. In a series of studies, we have reported racial disparities in the clinical presentation and the treatment outcomes for patients (pts) with DLBCL in the United States (Shenoy Cancer 2010; Flowers CEBP 2012). These studies showed that black pts with DLBCL are diagnosed at an age a decade younger than whites, are more likely to have advanced stage disease, and are less likely to survive 5 years. One explanation is that black patients in the US less often receive standard of care therapy (Flowers CEBP 2012). However, in a cohort study of 533 white and 144 black patients with DLBCL managed at Emory and University of Alabama-Birmingham (UAB) black race predicted worse overall survival (OS) even when black and white pts received the same therapy (CHOP; Hazard ratio [HR] 1.8, p 60 years of age (p=0.04), 73% had stage III/IV disease vs. 56% (p=0.03), and 77% had an LDH〉ULN vs. 51% (p=0.04). There were no significant differences between the two racial groups in terms of sex, ECOG PS, presence of B-symptoms (38% vs. 29%p=0.46), extranodal sites (50% vs. 78% ≤ 1, p=0.27), IPI risk, or treatment received (RCHOP 46% vs. 40% p=0.93). By the Hans, Natkunam, Tally, and Choi algorithms black patients more commonly presented with the poor-risk ABC/non-GCB subtype (by Choi black 64% ABC vs. white 37%; p= 0.01, Table). After controlling for clinical confounders including age, sex, stage, LDH, performance status, presence of B-symptoms, race, treatment (RCHOP vs. other), and ABC subtype, being 〉60 years of age [HR 3.1 95% CI 1.3–7.2], being black (HR 3.5 95% CI 1.5–8.2), and receiving treatment other than RCHOP (HR 12.8, 95% CI 3.2–50.6) were associated with inferior OS. Conclusions: The rate of ABC DLBCL is significantly higher in black pts compared to white pts in this university-based cohort from the Southern United States. Additional studies confirming these findings in larger populations and examining the mutations associated with these differences are underway to address biological differences intrinsic to DLBCL that may in part explain comparatively adverse features and outcomes for black pts with DLBCL. Disclosures: Flowers: Celgene, Spectrum, Millennium, Gilead, Janssen: Research Funding; Genentech/Roche (unpaid), Millennium (unpaid), Celgene: Consultancy. Bernal-Mizrachi:Empire Genomics (not related to current work): Patents & Royalties. Sinha:Celgene: Research Funding. Jaye:Millenium Pharmaceuticals (For single lecture on immunohistochemical subtyping of large B cell lymphomas): Honoraria.

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: Targeted therapy is increasingly incorporated into the chemotherapy regimens of adult ALL. While the prognosis of BCR/ABL + (Philadelphia) ALL is well recognized; the significance of CD 20 postivity is unknown. We report the characteristics of 76 patients treated at Emory University between January 1999 and March 2005, divided into 2 groups based on CD 20 expression, as determined by flow cytometry. The CD 20+ patients presented with a higher WBC count and LDH, and lower platelet counts (table). In the CD 20+ group, 65% had pre B cell ALL and 8% had high grade B cell leukemia/lymphoma, whereas the CD 20- group consisted of 30% pre B cell ALL, 24% T cell ALL, and 10% had high grade leukemia/lymphoma. Of the 35 Ph+ ALL patients, 27 were CD20+ (20%) and 18 CD20- (51%). Patients were treated on clinical trials L20, ALL2, and more recently with the Hyper-CVAD regimen (n=32). Only 5 of the CD 20+ patients received rituximab in addition to chemotherapy. With a median follow-up of 320 days, 46% of patients in each group are alive, 35% and 38% relapsed in the CD 20+ and CD 20- group, respectively. In summary, we found that CD 20+ ALL patients present with higher WBC count and LDH, and a lower platelet count; although, due to our small sample size, these differences were not significant. Further follow up is needed to provide mature results on survival and remission. CD 20+ CD 20- p= Total numbers 26 50 Median Age (yrs) 45.2 (18–74) 44 (19–76) NS Median WBC (103/μl) 29.1 10 0.09 Median Platelet (103/μl) 35 65 0.11 Median LDH (IU) 894 500 0.05 Normal Cytogenetics 13 (50%) 21 (42%) NS Ph+ ALL 7 (26%) 18 (35%) NS CR within 60 days 20 (77%) 27 (54%) NS Primary Refractory 2 (8%) 6 (12%) 0.7 Relapse 9 (35%) 19 (38%) NS Alive at last follow up 12(46%) 23 (46%) NS Expired by d270 8 (36%) 11 (25%) NS

Description: Background Waldenstrom Macroglobulinemia (WM) is a hematological malignancy that affects 1500 people each year in the United States. Due to lack of literature on era comparative population-based analysis, we have analyzed Surveillance Epidemiology and End Results (SEER) data to evaluate the changes in incidence and survival patterns in the new millennium where modern therapeutic agents such as rituximab, immunomodulatory drugs and proteasome inhibitors were offered to WM patients; in contrast to the earlier period when they were non-existent. Methods The SEER 18 registry which includes data from 1973-2010 from 18 geographic areas including 28% of US representative population was used in analysis. ICD-O-3 code 9761 was used for identifying patients for this analysis. SEER* Stat 8.0.4 is used to calculate age-adjusted incidence and mortality rates based on race, gender, and age for patients. Age adjusted rates were used in this anlaysis to avoid confounding variables when comparing rates over time. Results We have included 4304 patients in the analysis (1244 patients diagnosed before 2000 and 3060 patients after 2000). The incidence rate of WM increased with age. The 10 year cumulative incidence rate per 100,000 by age stratification (80) are 0.02%, 0.40%, 1.01%, 2.14% and 2.98% respectively. Over the last decade the trend of incidence rate in WM has been steadily decreasing across all age groups (Figure 1). Median survival for all WM patients is 74 months (m) (70.2-77.8). Significant survival improvement was seen in the current era (median survival ≥2000 vs.

Description: Abstract 1628 Introduction: Historically, relapsed DLBCL and HL has been associated with a high cure rate with salvage regimens followed by high dose chemotherapy and stem cell transplant (ASCT). However, patients (pts) who relapse early following upfront chemotherapy and pts who fail to respond to salvage have a poor overall response rate (ORR) with additional salvage regimens and a poor prognosis even when consolidated with ASCT (von Tresckow & Engert, 2011; Gisselbrecht et al., 2010). At present there is no standard therapy in the third-line setting for pts with DLBCL and HL. We designed a regimen: vinorelbine (30mg/m2) & paclitaxel (175mg/m2) given on day 1; etoposide (100mg/m2) & cisplatin (20mg/m2) given on days 2–5; and cytarabine (2000mg/m2) on days 4 and 5 (VTEPA) for treatment of lymphoma pts with 1° refractory disease or relapse following salvage. In phase 1, VTEPA was safe with a 33% ORR following 1 cycle (Lonial et al, 2006). Design and Methods: To examine the effectiveness of VTEPA, we conducted an IRB approved retrospective review of consecutive cases of relapsed/refractory DLBCL and HL identified from our database from 1999–2011. All pts had evidence of primary refractory disease or stable or progressive disease following first line salvage therapy. Responses following salvage VTEPA were retrospectively assessed using International Working Group Criteria (JCO 1999) for all pts. Responding pts proceeded to ASCT. Survival curves were constructed using the Kaplan-Meier method and compared with the log-rank test. Results: 74 pts (44 DLBCL and 30 HL) with a median age at diagnosis of 30 years (range 18–63) for HL and 49 years (range 20–68) for DLBCL were included. 67% of HL pts had primary refractory disease and 33% of pts had relapsed disease; 60% were stage III/IV at diagnosis. 75% of DLBCL pts had primary refractory disease and 25% of pts had relapsed disease; 73% stage III/IV. Pts received a median of 2 prior therapies (range 1–4). 63% pts with HL received prior salvage therapy with ifosfamide, carboplatin, and etoposide (ICE) and 13% with other regimens. 16 pts with HL received 1 cycle of VTEPA, 13 received 2 cycles and 1 pt received 3 cycles of VTEPA. 70% pts with DLBCL had received prior salvage therapy with rituximab (R) + ICE and 16% received other salvage regimens. 32 pts with DLBCL received 1 cycle of R-VTEPA and 12 pts received 2 cycles. The most common reported grade 3/4 toxicities were pancytopenia (97%), nausea/vomiting (58%), fatigue (30%), infectious complications (26%), diarrhea (24%), electrolyte imbalance (19%), and mucositis (16%). 70 pts (43 DLBCL and 27 HL) were evaluable for response. The ORR for DLBCL pts was 44% (9% CR and 35% PR) while that for HL pts was 70% (26% CR and 44% PR, p=0.04). 4 DLBCL pts had treatment related mortality. 34 pts went on to collect ≥2 × 106 CD34+ cells/kg; 3 pts had inadequate stem cell collection. In 23 pts collection was not attempted, and 14 pts collected stem cells prior to R+/−VTEPA. 37 pts (47%) went onto planned ASCT, and 4 pts underwent allogeneic transplantation. The PFS at 2 years for pts with HL was 68% vs. 49% for pts with DLBCL (p