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Abstract Background: Patients (pts) with aggressive NHL who relapse after conventional chemotherapy or stem cell transplant have a poor prognosis. Novel agents are needed for this important subset. Tipifarnib is an orally available methylquinolone derivative that is an inhibitor of the farnesyl transferase enzyme that transfers the farnesyl group from farnesyl pyrophosphate to specific polypeptides including small GTPases of the Ras, Rho-B, and Rheb families, as well as nuclear lamins and kinetochore proteins. Tipifarnib has documented activity in acute leukemia and produces stable disease in relapsed multiple myeloma. The goal of this study was to evaluate the activity of single-agent tipifarnib in patients with relapsed aggressive NHL in the context of a phase II trial. Methods: Pts with relapsed diffuse large, follicular grade III, or mantle cell lymphoma were eligible for this study. Pts were treated with oral tipifarnib 300 mg twice daily d1–21 q 28 days until progression. Pts were restaged after 2 cycles, 6 cycles, and every 3 cycles thereafter. Tumor was sampled prior to tipifarnib and at day 8 in selected patients with accessible tumors. These paired samples were assayed for accumulation of unprocessed HDJ-2 and prelamin A, two polypeptides that require farnesylation for processing. Results: Forty-two pts were accrued between March 2004 and June 2006. Thirty-seven pts had diffuse large cell, 1 follicular grade III, and 4 had mantle cell. Of the 38 patients evaluable for response, 7 (18%) had a partial response and 8 (21%) had stable disease. The 7 responders all had diffuse large cell histology. Median progression-free survival (PFS) for all pts was 2 months (range, 0–25+). The PFS of the 7 responders was noteworthy at 4.2, 4.9+, 6.7, 9.6, 14.9+, 21.6+, and 25.1+ months, respectively. The primary toxicity was myelosuppression and 33% of pts required dose reductions. The median dose received in all pts was 300 mg twice daily (mean 275, range, 100–400). The median dose received by the 7 responders was 200 mg twice daily (range, 100–400). The dose of 300 mg twice daily resulted in accumulation of unfarnesylated forms of one or both markers in all pts studied to date. Conclusion: Oral tipifarnib has antitumor activity as a single agent with an excellent toxicity profile in pts with relapsed/refractory aggressive lymphoma. When given in this dose and schedule, tipifarnib is well-tolerated and can be taken for months without cumulative toxicity. This drug warrants further investigation in combination with conventional chemotherapy and other novel agents for the treatment of this important subset of patients.

Abstract Abstract 1222 Poster Board I-244 Background Survival for patients with primary CNS lymphoma (PCNSL), in general, is poor with patients requiring frequent chemotherapy treatments or receiving whole-brain radiation therapy, which can potentially result in significant neurologic decline and dementia. Because of the improved survival of high risk patients with aggressive lymphoma undergoing autologous stem cell transplant (ASCT), we began ASCT for patients with PCNSL in first or later remission with chemotherapy sensitive disease. We now update on outcomes of patients who have had at least 100 day follow up post ASCT. Baseline characteristics Between June, 2000 and January, 2009, 22 patients underwent ASCT for PCNSL. Median age at transplant was 50 years old (range 26-67). Median number of prior treatments 1 (range 1-3). Median time from diagnosis to transplant was 7.2 months (range 2.9 to 75.8). Median International Extranodal Working Study Group Prognostic Score: 2 (range 0-3). Disease status at transplant: First CR 10 patients, later CR or PR 12 patients. Results Twenty-two patients underwent ASCT for PCNSL and have a minimum of 100 days follow-up. All patients received BEAM conditioning. Median follow up post-transplant was 30 months (range 3-107 months). Eight patients have relapsed at a median of 217 days (range 40-1349). Of the patients who relapsed, four have died of disease progression and the remaining four are alive after additional therapy. Median overall survival from diagnosis or transplant has not been reached. Median progression free survival from transplant was 70 months. Conclusions Although limited by patient selection and retrospective biases, this review suggests that ASCT for PCNSL demonstrates improved overall survival when compared to historical controls with similar PCNSL Prognostic Scores (2 year survival for patients from diagnosis with PS 2-3 was 48% in a prior published study). ASCT in first remission in patients with PCNSL appears promising and may limit the need for additional therapy which can be myelosuppressive or result in neurologic decline secondary to radiation therapy in patients who are appropriate candidates. Disclosures No relevant conflicts of interest to declare.

AbstractBackgroundThe extent to which obesity and genetics determine postoperative complications is incompletely understood.MethodsWe performed a retrospective study using two population cohorts with electronic health record (EHR) data. The first included 736,726 adults with body mass index (BMI) recorded between 1990 and 2017 at Vanderbilt University Medical Center. The second cohort consisted of 65,174 individuals from 12 institutions contributing EHR and genome‐wide genotyping data to the Electronic Medical Records and Genomics (eMERGE) Network. Pairwise logistic regression analyses were used to measure the association of BMI categories with postoperative complications derived from International Classification of Disease‐9 codes, including postoperative infection, incisional hernia, and intestinal obstruction. A genetic risk score was constructed from 97 obesity‐risk single‐nucleotide polymorphisms for a Mendelian randomization study to determine the association of genetic risk of obesity on postoperative complications. Logistic regression analyses were adjusted for sex, age, site, and race/principal components.ResultsIndividuals with overweight or obese BMI (≥25 kg/m2) had increased risk of incisional hernia (odds ratio [OR] 1.7–5.5, p < 3.1 × 10−20), and people with obesity (BMI ≥ 30 kg/m2) had increased risk of postoperative infection (OR 1.2–2.3, p < 2.5 × 10−5). In the eMERGE cohort, genetically predicted BMI was associated with incisional hernia (OR 2.1 [95% CI 1.8–2.5], p = 1.4 × 10−6) and postoperative infection (OR 1.6 [95% CI 1.4–1.9], p = 3.1 × 10−6). Association findings were similar after limitation of the cohorts to those who underwent abdominal procedures.ConclusionsClinical and Mendelian randomization studies suggest that obesity, as measured by BMI, is associated with the development of postoperative incisional hernia and infection.

Abstract Background: Isolated brain parenchyma relapse as initial site of relapse is a rare complication of NHL and carries a poor prognosis. Few large series focus on treatment characteristics and outcomes of isolated brain parenchyma relapse of NHL. Methods: The IPCG conducted a retrospective review of patient and treatment characteristics and outcomes of this complication. Following initial diagnosis and treatment of NHL (1980–2004), cases with brain parenchyma relapse as initial relapse site, with no evidence of lymphoma elsewhere in the body at the time of brain relapse, were eligible. Cases with brain, spine or leptomeningeal involvement at NHL diagnosis were not eligible. Results: 113 cases were assembled from 13 investigators in 8 countries. Preliminary data summaries are: 94 (83%) cases had diffuse large B-cell NHL, 5 (4%) follicular lymphoma, 3 (3%) Burkitt’s lymphoma, other NHL subtypes (11) . Median age at NHL diagnosis was 61yrs (16–85 yrs). 55% were male. Median ECOG at NHL diagnosis was 1. Median time from NHL diagnosis to isolated brain relapse was 1.8 yrs (3 months–15.9 yrs). 76 (67%) relapsed in brain less than 3 yrs after NHL diagnosis. Symptoms at brain relapse included mental status changes in 37%, gait/balance disturbance (27%), motor/sensory symptoms (23%). Median ECOG at brain relapse was 2. Parenchyma relapse was documented by brain imaging plus biopsy in 54 (48%), or imaging without biopsy in 58 (52%); not reported (1). 53 (48%) cases had one brain lesion; 56 (50%) had two or more lesions; not reported (4). Site of relapse was cerebral hemispheres in 53 (48%) cases, deep brain structures (brain stem/cerebellum) in 30 (27%), cerebral hemispheres and deep brain structures in 23 (21%); not reported (7). At brain relapse, CSF was positive in 11 (10%) cases, negative in 56 (50%); not reported (46[40%]). Treatment for brain relapse was chemotherapy alone in 52 (46%) cases, WBRT alone in 34 (30%), chemotherapy followed by RT in 26 (23%), and brain surgery alone (1). 78 (69%) cases are deceased. Median survival from brain parenchyma relapse to death was 1.6 yrs (95% CI: 11 months–2.6 yrs). Effect of treatment type at brain relapse on survival, will be reported. Brain lymphoma was the cause of death in 49 (63%) cases; CNS toxicity was the cause in 6 (8%) cases. Conclusion: Though a rare relapse site, prospective studies are needed to improve understanding and outcomes of isolated brain parenchyma relapse of NHL.

Abstract Background: Absolute lymphocyte count (ALC) recovery is an independent prognostic factor for survival for different hematological malignancies treated with autologous stem cell transplantation. Recently, we reported superior overall survival (OS) in patients with follicular lymphomas that presented with a higher ALC (ALC ≥ 1 x 109/L) at diagnosis. The role of ALC at diagnosis on survival in T cell lymphomas is not known. Methods: All patients evaluated at the Mayo Clinic for T cell lymphomas from October 1984 until April 2005 were analyzed in the study. The primary objective of the study was to assess the role of ALC at diagnosis and survival in T cell lymphomas. ALC at diagnosis was obtained from the standard complete blood cell count (CBC). Results: 223 patients with T cell lymphomas were included in the study. The histology included: peripheral T-cell lymphoma-unspecified (40%), anaplastic large cell (13%), angioimmunoblastic (10%), angiocentric (4%), intestinal T-cell (2%), and other (31%). The median follow-up was 18.6 months (range: 1 month – 229 months [19 years]). The sample population included 60% male and 40% females with a median age of 60 years (15–90 years). The median ALC at diagnosis was 1.2 x 109/L (range: 0.04–6.7 x 109/L). ALC as a continuous variable was identified as predictor for OS in the univariate analysis (HR= 0.690, 95%CI: 0.542–0.862, p < 0.0006). ALC ≥ 1 x 109/L was selected as the dichotomized value because it yielded the maximum difference in survival by c2 analysis looking at different cut-point from 0.6 to 1.7 x 109/L that were included between the 25% and 75% quartiles. Univariately, ALC ≥ 1 x 109/L was also identified as a predictor for OS (HR = 0.682, 95%CL= 0.578–0.804, p < 0.0001). Patients (N = 122) with an ALC ≥ 1 x 109/L experienced superior survival compared to patients (N = 101) with an ALC < 1 x 109/L [median OS: 76.3 vs 10.6 months, respectively; and 5 years OS estimates of 53% vs 23%, respectively, p < 0.0001]. When ALC ≥ 1 x 109/L was compared to the international prognostic index (IPI), ALC ≥ 1 x 109/L remained an independent predictor for survival in the multivariate analysis (HR = 0.779, 95%CL: 0.655–0.925, p < 0.004). Conclusion: This study demonstrates ALC as an independent predictor for OS in T cell lymphomas, suggesting that the host immune system affects survival in this group of patients.

Background: Treatment outcomes and risk factors for neurological deficits in pediatric patients with an os odontoideum are unclear. Methods: We reviewed the data for 102 children with os odontoideum who were managed at 11 centers between 2000 and 2016 and had a minimum duration of follow-up of 2 years. Thirty-one children had nonoperative treatment, and 71 underwent instrumented posterior cervical spinal arthrodesis for the treatment of C1-C2 instability. Nonoperative treatment consisted of observation (n = 29) or immobilization with a cervical collar (n = 1) or halo body jacket (n = 1). Surgical treatment consisted of atlantoaxial (n = 50) or occipitocervical (n = 21) arthrodesis. One patient also underwent transoral odontoidectomy. Results: Thirty children (29%) presented with neurological deficits, 28 of whom had radiographic atlantoaxial instability (atlantoaxial distance >5 mm) or limited space (≤13 mm) available for the spinal cord (risk ratio, 7.8 [95% confidence interval, 2.0 to 31] compared with children with no radiographic risk factors). The 27 children without neurological deficits or atlantoaxial instability at presentation underwent nonoperative treatment and remained asymptomatic. Of the initial nonoperative cohort, one child developed atlantoaxial instability, and another had a persistent neurological deficit; both children underwent spinal arthrodesis during the study period. One child with cervical instability declined surgery and remained asymptomatic. Spinal fusion occurred in 68 patients in the surgical group by the end of the study period (mean, 3.7 years; range, 2.0 to 11.8 years). Surgical complications occurred in 21 children, including nonunion in 12, new neurological deficits in 4, cerebrospinal fluid leak in 2, symptomatic instrumentation requiring removal 2, and vertebral artery injury in 1. Nine children underwent revision surgery. In the surgical group, Japanese Orthopaedic Association neurological function scores improved significantly from preoperatively to the latest follow-up for the upper extremities (p = 0.026) and lower extremities (p = 0.007). Conclusions: The risk of developing a neurological deficit was strongly associated with atlantoaxial instability and limited space available for the spinal cord in children with os odontoideum. Nonoperative treatment was safe for asymptomatic patients without atlantoaxial instability. Spinal arthrodesis resolved the neurological deficits of children with symptomatic os odontoideum. Level of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

We showed in a phase I trial that the maximum tolerated dose of the ProMACE-CytaBOM regimen in patients with aggressive lymphoma was 200% (Gordon et al, J Clin Oncol 14:1275, 1996). Based on these observations, we initiated a phase II trial designed to determine response, toxicity, and dose intensity using this regimen. We analyzed 74 patients with advanced-stage (III or IV) or bulky stage II aggressive lymphoma. The overall complete response rate was 69% (72% in evaluable patients). With a median follow-up of 4.5 years, the median survival has not yet been reached. The 4-year survival rate is 73% (95% confidence interval [CI] 62, 83%) and no difference was observed among International Prognostic Index (IPI) groups. The 4-year disease-free survival was 71% (95% CI 58, 84%) with no statistical difference between patients with IPI 0 to 1 versus 2 to 4. The toxicity was acceptable, though the grade 4 hematologic toxicity rate for this regimen was 100%. Grade 4 nonhematologic toxicity was 36%. Three cases of either myelodysplastic syndrome or acute leukemia occurred at 7 months, 3.4 years, and 4.2 years after registration. Cytogenic analysis was available in two cases, showing inv(16) without French American British classification (FAB) M4 EO histology in one patient and a 5q-syndrome in the other. These data suggest that 200% ProMACE-CytaBOM with either granulocyte-macrophage colony-stimulating factor (GM-CSF) or G-CSF results in a high complete remission rate and a disease-free survival comparable to any prior risk-based analysis in aggressive lymphoma. Before using this regimen in general practice, phase III clinical trials should be conducted.

Abstract Abstract 1527 Interim Positron-Emission Tomography (PET-scan), as a functional imaging test for tumor activity, has been shown to be a predictor for progression-free survival (PFS) and time to progression (TTP) in classical Hodgkin lymphoma (HL). The peripheral blood absolute lymphocyte/monocyte ratio (ALC/AMC) at diagnosis, as a surrogate marker of host immunity (i.e., ALC) and tumor microenvironment (i.e., AMC), has been recently reported [Porrata et al, Hematologica 2012; 97(2): 262–9] and confirmed [Koh et al, Oncologist 2012; 17(6): 871–80] to be also a predictor for PFS and TTP in classical HL. Therefore, we evaluated the combination of ALC/AMC ratio at diagnosis and the interim PET-scan to further stratify the clinical outcomes of PFS and TTP in patients with classical HL. To participate in the studies, patients were required to be diagnosed, treated, and followed at Mayo Clinic, Rochester, Minnesota. The treatment consisted of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) with or without radiation therapy. Patients were required to have an interim PET-scan performed. An ALC/AMC ratio ≥1.1 cut-off was used in the study based on our previous publication [Porrata et al, Hematologica 2012; 97(2): 262–9]. From 2000 until 2008, 111 classical HL patients qualified for the study. The cohort included 54% males and 46% females. The median age at diagnosis was 37 years (range: 18–83 years). The median follow-up was 2.8 years (range: 0.3–10.4 years). Patients with a negative interim PET-scan (N=98) presented with a higher ALC/AMC ratio at diagnosis (median of 2.32, range: 0.26–37.5) compared with patients with a positive interim PET-scan (N = 13) (median of 0.9, range: 0.29–3.10), p < 0.004. By univariate analysis, the ALC/AMC ratio at diagnosis and the interim PET-scan were predictors for PFS [ ALC/AMC ratio, R =0.13, 95% CI (0.05–0.35), p < 0.0002; and interim PET-scan, HR = 0.13, 95% CI (0.05–0.37), p < 0.0003] and TTP [ALC/AMC ratio, R =0.07, 95% CI (0.02–0.24), p < 0.0001; and interim PET-scan, HR = 0.05, 95% CI (0.01–0.18), p < 0.0003]. By multivariate analysis, ALC/AMC ratio at diagnosis and the interim PET-scan were independent predictors for PFS [ ALC/AMC ratio, R =0.13, 95% CI (0.07–0.63), p < 0.006; and interim PET-scan, HR = 0.11, 95%CI (0.02–0.47), p < 0.003] and TTP [ALC/AMC ratio, R =0.11, 95% CI (0.02–0.71), p < 0.02; and interim PET-scan, HR = 0.10, 95% CI (0.02–0.46), p < 0.003] when compared to the International Prognostic Score, limited versus advanced stage, and radiation. Patients were stratified into four groups: group 1 included patients with a negative interim PET-scan and ALC/AMC ratio at diagnosis ≥1.1 (N = 88); group 2 included positive interim PET-scan and ALC/AMC ratio at diagnosis ≥1.1 (N = 5); group 3 included negative PET-scan and ALC/AMC ratio at diagnosis < 1.1 (N = 10); and group 4 included positive PET-scan and ALC/AMC ratio at diagnosis <1.1 (N = 8). The three year PFS rates for each group were for goup1 95% (Events = 6); group 2 40% (Events = 3); group 3 56% (Events = 4); and group 4 50% (events = 4), p < 0.0001. The three year TTP rates for each group were: for group1 was 100% (Events = 0); for group 2 of 40% (Events = 3); for group 3 of 65% (Events = 3); and group 4 of 50% (events = 4), p < 0.0001. In conclusion, the ALC/AMC ratio at diagnosis is independent of the interim PET-scan to predict PFS and TTP in classical HL. Further studies are warranted to confirm our findings and to assess if the combination of the ALC/AMC ratio at diagnosis and interim PET can be use for planning of risk-adapted treatment. Disclosures: Ansell: Seattle Genetics, Inc.: Research Funding.

Abstract Background: We recently clarified the use of consolidative autologous stem cell transplantation (ASCT) as first remission consolidation therapy for high grade diffuse aggressive T and B non-Hodgkin's lymphoma (NHL)in patients with high-intermediate (HI) or High (H) age adjusted IPI disease (Stiff et al, NEJM 369:1681). After receiving CHOP or R-CHOP for 5 cycles responding patients were randomized to either 3 more induction cycles or 1 cycle followed by an ASCT using either a BCNU or TBI based preparative regimen. We found a PFS but not OS advantage for those randomized to transplant and no differential treatment effect for those with T-NHL patients as compared to B-NHL in the initial analysis of this study. In light of Phase II data suggesting a value of early ASCT for T-NHL, a lack of randomized ASCT trials for T-NHL and the inferior prognosis for T-NHL as compared to B cell disease, we further evaluated this sub group, since a post hoc analysis of the entire trial did find a survival advantage for those with H IPI disease. This then provided a unique opportunity to evaluate the role of ASCT consolidation for T-cell NHL in the setting of a prospective randomized trial. Method: Among the 370 eligible B-NHL and T-NHL patients with HI/H IPI disease treated on this trial, 40 had a T-NHL phenotype and were the subject of this analysis. Individual patient files were re-reviewed and those randomized after the first 5 cycles of CHOP were further analyzed for stage, IPI group, histology (centrally reviewed), and response to induction and consolidation and updated survival outcome. Results: Of the 40 T-NHL patients enrolled on study, 28 (70%) were randomized after induction therapy, a similar ratio to the entire trial (68%). Twelve were not randomized; 1 was ineligible for study, and of the eligible 11, 9 were HI IPI and 8 had peripheral T cell (PTCL-NOS). These 11 were not randomized due to patient choice in 2, and all of the remaining 9 pts progressed early: 2 after C1; 3 after C3, 1 after C4, and 3 after C5. For the 28 randomized, their median age was 50 and 19 were males. Of the group, 21/28 had B symptoms at diagnosis, 14 had stage IV disease, and 18 and 10 were in the HI and H IPI groups respectively. Histologies included 11 with PTCL-NOS, 7 angioimmunoblastic and 10 anaplastic large cell NHL. At randomization 13 were to continue CHOP and 15, ASCT. Of the 15 assigned to ASCT, 3 did not undergo transplant (2-refusals, 1- unable to mobilize); 7 received the BCNU-etoposide-cyclophosphamide and 5 the TBI-etoposide-cyclophosphamide preparative regimen. The 5 year estimates of PFS and OS for the randomized ASCT vs CHOP only groups (intent to treat) were 40% vs 38% (p=0.56) and 40% vs 45% (p=0.98) respectively. We found no difference in outcome based on IPI group, histology or stage of disease. Interestingly, only 1/7 patients who received BCV as the ASCT preparative regimen are long term survivors vs 4/5 receiving the TBI-based regimen. Conclusions: We did not observe a PFS/OS advantage for those with high-risk T-NHL in first remission randomized to ASCT following CHOP induction vs CHOP alone in this retrospective analysis. In addition, the 30% early drop out rate before randomization due primarily to early progression strongly suggests that more optimal induction regimens need to be developed for this disease. While the numbers are small the finding that TBI based preparative regimens might be associated with a higher PFS is of interest and deserves further study. Support: NIH/NCI grants CA180888 and CA180819; Bristol-Myers Squibb. Contributions of Dr. Raymond R Tubbs, deceased, are gratefully acknowledged. Figure 1 Figure 1. Disclosures Porcu: miRagen: Other: Investigator in a clinical trial; celgene: Other: Investigator in a clinical trial; Millenium: Other: investigator in a clinical trial; Innate Pharma: Other: Investigator in a clinical trial. Winter:Pharmacyclics: Research Funding; Medivation: Other: Provision of investigational agent for clinical trial; Seattle Genetics: Research Funding; GSK: Research Funding. Kahl:This study was coordinated by the ECOG-ACRIN Cancer Research Group (Robert L. Comis, MD and Mitchell D. Schnall, MD, PhD, Group Co-Chairs) and supported by the National Cancer Institute of the National Institutes of Health under the following award number: Research Funding. Smith:Juno: Consultancy; TGTX: Consultancy; AbbVie: Consultancy; Celgene: Consultancy; Genentech: Consultancy, Other: on a DSMB for two trials ; Gilead: Consultancy; Portola: Consultancy; Amgen: Other: Educational lecture to sales force; Pharmacyclics: Consultancy. Rimsza:NCI/NIH: Patents & Royalties: L.M. Rimsza is a co-inventor on a provisional patent, owned by the NCI of the NIH, using Nanostring technology for determining cell of origin in DLBCL.. Fisher:Gilead: Consultancy; Seattle Genetics: Consultancy; Johnson and Johnson: Consultancy. Friedberg:Bayer: Honoraria, Other: Data Safety Monitoring Board.

Abstract Abstract 2740 Background: Historically, treatment options for the approximately 30% of patients with Hodgkin lymphoma (HL) who have primary refractory disease or relapse after experiencing initial response have been limited to high-dose chemotherapy with autologous hematopoietic stem cell transplant (AHSCT). Development of novel therapeutic options is needed to improve outcomes in patients whose disease is refractory to or relapses after initial chemotherapy or subsequent high-dose chemotherapy with AHSCT. The oral mammalian target of rapamycin inhibitor everolimus showed promising efficacy and acceptable toxicity in 19 patients with heavily pretreated HL enrolled in a phase 2 study of everolimus monotherapy for relapsed, rare lymphomas (Johnston et al. Am J Hematol 2010;85:320-4). To confirm the efficacy and safety of everolimus monotherapy in patients with relapsed/refractory classical HL, we conducted a multicenter, open-label, 2-step, phase 2 study. Methods: Adults with classical HL that progressed after high-dose chemotherapy with AHSCT or a gemcitabine-, vinorelbine-, or vinblastine-containing regimen received everolimus 10 mg/day until disease progression or unacceptable toxicity. Response was assessed every 12 weeks via computed tomography with contrast or integrated positron emission tomography/computed tomography with contrast. The primary study endpoint was the overall response rate (ORR) evaluated according to the modified response criteria for malignant lymphoma (Cheson et al. J Clin Oncol 2007;25:579-86). Secondary endpoints included the disease control rate (DCR), duration of overall response, duration of disease control, progression-free survival (PFS), and safety. Results: A total of 57 patients were enrolled in this study; 57.9% were women, the median age was 32.0 years, 57.9% were pretreated with AHSCT, and 100% were pretreated with gemcitabine, vinorelbine, or vinblastine. Overall, 66.7% of patients experienced disease progression during previous therapies or discontinued previous treatment due to progression. At the time of analysis, 48 patients discontinued study treatment, most commonly due to disease progression (n = 25). The ORR and DCR were 42.1% and 77.2%, respectively (Table). The median time to response was 57 days. Median PFS was 9.0 months. Adverse events experienced by >25% of patients were fatigue (56.1%), thrombocytopenia (47.4%), cough (38.6%), rash (38.6%), pyrexia (31.6%), anemia (29.8%), dyspnea (28.1%), back pain (26.3%), and diarrhea (26.3%). Grade 3/4 adverse events were observed in 33 patients (57.9%); the most common were thrombocytopenia (21.1%) and anemia (12.3%). Stomatitis was experienced by 14 patients (24.6%) and was of grade 3 severity in 2 patients (3.5%). Pneumonitis was observed in 6 patients (10.5%) and was of grade 1 severity in 2 patients (3.5%) and grade 2 severity in 4 patients (7.0%). Conclusions: In this phase 2 study, everolimus monotherapy demonstrated favorable efficacy and a short time to response in patients with heavily pretreated, relapsed/refractory classical HL. The overall safety profile was consistent with that previously observed for everolimus in patients with HL and other cancers. The results of this study confirm previous results and support the further evaluation of everolimus in patients with classical HL. Disclosures: Johnston: Novartis: Consultancy. Off Label Use: Everolimus is an mTOR inhibitor indicated in the US for the treatment of postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer in combination with letrozole after failure of letrozole or anastrozole; adults with progressive pancreatic neuroendocrine tumors that are unresectable, locally advanced, or metastatic; adults with advanced renal cell carcinoma after failure of treatment with sunitinib or sorafenib; adults with renal angiomyolipoma and tuberous sclerosis complex not requiring immediate surgery; and adults and children aged 3 years or greater with subependymal giant cell astrocytoma associated with tuberous sclerosis complex who require therapeutic intervention but are not candidates for curative surgical resection. Pinter-Brown:Millennium: Consultancy. Rogerio:Novartis: Employment; Novartis: Equity Ownership. Warsi:Novartis: Employment; Novartis: Equity Ownership. Chau:Novartis: Employment. Ramchandren:Seattle Genetics: Honoraria.