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We present the rare case of a 71 year old man with intracranial primary dural Hodgkin lymphoma (PDHL). He underwent subtotal resection of the mass, followed by adjuvant chemotherapy and consolidative radiotherapy, with no recurrence at 5 years follow up.

e18780 Background: Patients with hematologic malignancies have a lower vaccine response and higher rates for SARS CoV-2 morbidity and mortality. We present preliminary data focusing on humoral vaccine responses and correlates with disease subtype and treatment exposure. Methods: We analyzed data from 332 patients with a hematologic malignancy from May 1, 2021 – Jan 31, 2022 who received SARS-CoV-2 vaccination and performed a prospective cohort serologic study with the Elecsys® Anti-SARS-CoV-2-S test. Patients received homologous or heterologous vaccine combination of BNT162b2, mRNA1273, ChAdOx1 nCoV-19, and/or Ad26.COV2.S. Blood samples were obtained before any vaccination, 2-6 weeks after the second vaccine (2V), before third vaccine (3V), and 2-6 weeks after 3V. Results: The median age was 67 years (range 18-91years) with 41.9% female. At 2V, 11.5% and at 3V, 23.8% received heterologous vaccines. Treatment status at first vaccine dose significantly affected peak 2V antibody response (p < 0.05). Seropositive rate and median antibody titer after 2V for previously untreated patients were higher compared to patients on active therapy or had previously been treated. Treatment naïve (n = 60; seropositivity 85.1%; median titer 1306 U/mL; [Q1-Q3:11.4- > 2499]); first-line (1L) active therapy (n = 127;65.4%; 41.25 U/mL; [ < 0.8-592.5]); second-line and beyond (2L+) active therapy (n = 56; 60.7%; 2.6U/mL; [ < 0.8-154]); previous treatment with 1L (n = 66;64.8%; 118 U/mL; [ < 0.8- > 2499]); previous treatment with 2L+ (n = 23; 59.1%; 4U/mL; [ < 0.8-229.5]). Of 61 patients that were seronegative at 2V, 17 (27.9%) seroconverted after 3V. Anti-CD20 monoclonal antibody (mAb) containing therapy as the most recent treatment from 2V had the greatest impact on humoral response. Exposure to anti-CD20 mAb based regimens or as monotherapy revealed low antibody responses (n = 84; seropositivity 22.6%; median titer < 0.8 U/mL; Q1-Q3 [ < 0.8- < 0.8]). On analysis of indolent B-cell Non-Hodgkin Lymphomas whereby antiCD-20 mAb are often incorporated, treatment proximity to 2V impacted responses: < 3 months (n = 33; 22%; < 0.8 U/mL; [ < 0.8- < 0.8]) vs. 12-24 months (n = 4; 60%; 228 U/mL; [ < 0.8-232]). In contrast, tyrosine kinase inhibitor (n = 38; 100%; 858 U/mL; [221- > 2499]), proteosome inhibitor monotherapy (n = 4;100%; median titer 1520 U/mL; [462- > 2499]) were among the subgroups with the highest numerical responses, however, the addition of corticosteroids impacted vaccine response as seen in proteosome inhibitor with corticosteroids (n = 7; 85.7%; 6.6 U/mL; [1.8-115.2]). Conclusions: The humoral response from our single institution cohort identifies diminished responses depending on treatment status and the type of treatment including the proximity of treatment exposure to receipt of vaccination. Furthermore, vaccine boosters can induce antibody responses in patients who were previously seronegative.

Background Treatment of recurrent/refractory (r/r) DLBCL remains an unmet clinical need, and new effective and well-tolerated treatments are required. DPX-Survivac is a unique T cell activation therapy that targets survivin-expressing tumor cells and has shown anti-tumor activity in clinical trials. This trial is evaluating a novel immunotherapy combination with DPX-Survivac, intermittent low dose CPA and pembrolizumab. Methods ‘SPiReL’ is a Phase 2 non-randomized, open label, efficacy and safety study of a novel immunotherapy combination with DPX-Survivac (a unique T cell activation therapy that targets survivin-expressing tumor cells), intermittent low dose CPA and pembrolizumab, treatment regimen as described in figure 1. Subjects with r/r incurable DLBCL and survivin expression are eligible for participation. This study was approved by the Ontario Cancer Research Ethics Board, approval number 0981.ORR is assessed by modified Cheson criteria. For translational analyses, baseline and on-treatment PBMCs, along with tumor biopsy samples are collected from each subject. Survivin-specific systemic T cell responses are assessed using IFNγ-ELISPOT assay and tumour immune-infiltrate profile by multiplex-IHC. Results Twenty-two subjects have been enrolled to date, 19 are included in the intent to treat (ITT) population and 11 subjects are evaluable in the per protocol (PP) population. In the PP, the ORR is 63.6% including 3 CRs (27.3%), 4 PRs (36.4%) and the DCR is 81.8% (9/11). In the ITT, the ORR is 35% (7/19), and DCR is 52.0% (10/19). Preliminary results show that non-GCB subjects had a higher proportion of clinical response (4/8, 50%), compared to 3/10 (30%) in GCB subjects.DPX-Survivac-induced T cell responses were observed in 8/19 subjects (42.1%) including 6 subjects with clinical response (PR, CR), one SD and one PD. Multiplex-IHC analyses demonstrated baseline tumor PD-L1 expression in 6/7 subjects with a clinical response (85.7%, p Conclusions DPX-Survivac, intermittent low-dose CPA and pembrolizumab is generally well tolerated and can induce clinical responses in subjects with r/r DLBCL (7/11, 63.6% of evaluable subjects), including subjects with both non-GCB and GCB subtypes. Pre-treatment biopsies of clinical responders were characterized by higher baseline tumor PD-L1 expression and CD4 and CD8 infiltration. Extending this exploratory data in a larger cohort may define a r/r DLBCL patient population with a higher likelihood to respond to this novel combination immunotherapy. Trial Registration NCT03349450 Ethics Approval This study was approved by the Ontario Cancer Research Ethics Board, approval number 0981.

Introduction: Febrile neutropenia (FN) is a serious potential adverse event of myelosuppressive chemotherapy. Dose-adjusted EPOCH-R (DA-EPOCH-R: etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab, with doses adjusted to induce neutropenia of < 0.5 x 10 9/L) is a chemoimmunotherapy regimen used for aggressive lymphomas including diffuse large B-cell lymphoma, double/triple hit, Burkitt, primary mediastinal, and HIV-associated large cell lymphoma. It is associated with high rates of FN (13-25% of cycles) despite use of prophylactic Septra and granulocyte colony stimulating factor (G-CSF). Fluoroquinolone antibiotics have been used in various hematological malignancies to reduce infection rates while on chemotherapy, but this strategy has never been reported with DA-EPOCH-R. This study was conducted to assess the impact of adding routine Levofloxacin prophylaxis on FN and infection rates in patients receiving DA-EPOCH-R. Methods: This is a combined cohort study comparing the patients who received DA-EPOCH-R for newly diagnosed aggressive lymphoma at the London Regional Cancer Program in London, Ontario, Canada before and after the initiation of routine Levofloxacin prophylaxis in July 2020. The prospective cohort received Levofloxacin 500 mg x 7 days with each cycle starting on cycle day 8 in addition to standard supportive care with Septra and G-CSF. The primary objective was the rate of febrile neutropenia. Secondary objectives included days hospitalized, deaths related to infections, and adverse events secondary to Levofloxacin. Results: Thirty patients who received DA-EPOCH-R in the 5 years preceding the initiation of routine prophylactic Levofloxacin were included in the retrospective cohort. Median age was 58 (range 18-79), 66% were male, and 90% had stage III/IV disease. Total number of cycles of DA-EPOCH-R received was 110, with a median of 4 cycles per patient (range: 1-6). FN developed in 14 patients (46%), and complicated a total of 20 cycles (18%) of DA-EPOCH-R. There were 19 hospital admissions due to FN, with a median duration of hospitalization of 12 days (range 3-120). Two patients died, both due to infection. Thirteen patients have been treated so far in the prospective cohort, 12 of whom received levofloxacin prophylaxis. Median age was 59 (range 23-69), 66% were male, and 76% had stage III/IV disease. Total number of cycles of DA-EPOCH-R received was 60, with a median of 5 cycles per patient (range: 1-6 ). Only 1 patient (8%) developed FN, which complicated a total of 3 cycles (5%) of chemotherapy. All 3 episodes of FN resulted in hospitalization for a median duration of 30 days (range 20-49). There have been no deaths due to infection in this cohort thus far. No concerning adverse effects from Levofloxacin have been observed. Conclusions: Although enrollment in the prospective cohort is ongoing, preliminary data are highly encouraging, with significantly lower rates of FN and death due to infection observed since the introduction of routine Levofloxacin prophylaxis. The addition of Levofloxacin to standard prophylaxis with Septra and G-CSF seems to be an effective way to mitigate the risks to patients on DA-EPOCH-R for aggressive lymphomas, and this strategy is worthy of further study. Disclosures Lam: Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Hoffmann-La Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Beigene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: 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; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Honoraria, Membership on an entity's Board of Directors or advisory committees; SeaGen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Phua: NovoNordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria.

Introduction: Ibrutinib, an oral Bruton Kinase inhibitor, is a highly effective treatment for patients with chronic lymphocytic leukemia (CLL). Previous studies reported an increased risk of bleeding due to impaired platelet function. Patients with CLL experience significant thrombocytopenia, which increases their risk for bleeding. This population was excluded from major trials and data is lacking to inform management in this setting. Methods: This is a single center retrospective study of all adult patients with CLL who received single agent ibrutinib in London, Ontario, Canada between January 2014 to December 2020. The primary objective was to investigate the risk of major bleeding associated with thrombocytopenia. Secondary objective was to investigate potential predictors of bleeding. Bleeding events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) grading system. A major bleed was defined as CTCAE grade 3 or higher as well as bleeding in the central nervous system. To assess the effect of independent variables on the outcome of bleeding, univariate analysis using chi square and t-tests was performed. Multivariate analysis was then preformed with the variables that were significant (p Results: A total of 170 patients were included in this study. There were 54 bleeding events documented in 42 patients (24.7 %) of which 19(35 %) were major bleeding occurring in 17 patients. Median time to major bleeding was 2.4 months. Of the patients with major bleeding, 4(21%) were on anticoagulation, 2(10%) were on antiplatelet and 2(10%) were on combined anticoagulation and antiplatelet. There were 8 central nervous system (CNS) bleeding and 2 of them died. The mean platelet (PLT) nadir, defined as lowest PLT count at any point during ibrutinib treatment, was 73 x 10 9/Lin patients with major bleeding compared to 116 x 10 9/L in patients with minor and 91 x 10 9/L in patients with no bleeding events. On the univariate analysis, when compared patients with major bleeding to patients with no bleeding, potential predictors of major bleeding included PLT nadir (p=0.09), haemoglobin (Hb) < 100 g/L at ibrutinib initiation (p=0.027) and anticoagulation (p=0.009). When compared patients with major bleeding to patients with minor or no bleeding, potential predictors of major bleeding included PLT nadir (p=0.045), Hb To confirm the significance of these variables, multivariate analysis was performed. When compared patients with major bleeding to patients with no bleeding, PLT nadir (OR= 0.9, p=0.008) and anticoagulation (OR=4.02, p=0.001) were confirmed to be the potential predictors of major bleeding. When compared patients with major bleeding to patients with minor or no bleeding, PLT nadir (OR=0.9 p=0.005) and Hb Conclusions: Although not common, Ibrutinib is associated with increased risk of bleeding and identifying high risk patients is essential to prevent major bleeding events. This retrospective Canadian study was done with the primary objective to assess the association between PLT count and major bleeding in patients on ibrutinib for treatment of CLL. In this analysis patients with major bleeding tend to have lower PLT counts compared to patients with minor or no bleeding, with mean PLT nadir of 73x 10 9/L. However, grade 3 thrombocytopenia (PLT nadir Figure 1 Figure 1. Disclosures Louzada: Amgen: Honoraria; Pfizer: Honoraria; Celgene: Honoraria; Janssen: Honoraria. Lam: AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Hoffmann-La Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; SeaGen: 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; Bristol-Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Beigene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees. Phua: Amgen: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; NovoNordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria.

BACKGROUND Between March 2012 and March 2013, a miscommunication in labelling between the drug compounder supplier and cancer centre pharmacies resulted in accidental overdilution of cyclophosphamide and gemcitabine used by several cancer centres in Canada. At our centre, 177 hematology patients were affected, among whom the largest subset of patients was those with diffuse large B-cell lymphoma. In this study, we evaluated the effect of such underdosing on disease response. METHODS We conducted a retrospective cohort study involving all patients with diffuse large B-cell lymphoma who received at least 1 chemotherapy cycle containing diluted cyclophosphamide at our centre and compared them with a historical group of patients matched by stage and age. The primary outcome was event-free survival (a composite of disease progression or death). Secondary outcomes included complete remission and overall response rate. Groups were compared using unpaired Student t, χ2 or Fisher exact tests, as appropriate. Survival analysis was done using the Kaplan-Meier method. RESULTS Event-free survival was no different between groups (log-rank p = 0.99). At a median follow-up of 548 days, progression or death occurred in 21 of 77 patients in the case group (27.3%) and in 24 of 74 patients in the control group (32.4%) (p = 0.5). At the end of treatment, complete remission was achieved in 41 patients in the case group (53.2%) and 43 patients in the control group (57.3%) (p = 0.6), whereas overall response rate was 71.4% in the case group and 66.7% in the control group (p = 0.5). INTERPRETATION Compared with a historical control group, we found no differences in event-free survival or response rates among patients with diffuse large B-cell lymphoma who received 1 or more doses of accidentally diluted cyclophosphamide-containing chemotherapy.

Background: Recurrent/refractory (r/r) DLBCL presents a major treatment challenge, especially in the setting of patients who are ineligible for, or relapsing after, potentially curative treatments such as autologous stem cell transplant (ASCT) and chimeric antigen receptor T cell (CAR-T) therapy. Efficacious treatment options that are well-tolerated and easily accessible in this population represent a critical unmet medical need. DPX-Survivac is a targeted T cell activation therapy against cancers expressing survivin. Survivin plays an essential role in cancer biology and represents a target of choice to disrupt tumour progression. DPX-Survivac's mechanism of action relies on its ability to generate robust and durable survivin-specific T cells that migrate to, infiltrate and kill tumour cells. DPX-Survivac is administered with intermittent, low dose cyclophosphamide (CPA) used as an immunomodulator. In nonclinical studies, treatment with DPX-Survivac increases PD-L1 and PD-1 expression providing the rationale for combination with pembrolizumab. Methods: "SPiReL" is a Phase 2 non-randomized, open label, efficacy and safety study. Subjects with r/r DLBCL with confirmed survivin expression are eligible for participation. Subjects must also be ineligible for potentially curative therapy. The treatment and testing regimen is shown in the figre below. The primary objective of SPiReL is to document a minimum Objective Response Rate (ORR) of 24% (in 6/25 subjects) using the modified Cheson criteria (2007). Secondary objectives include safety, duration of response and time to next treatment. Exploratory endpoints include T cell response, tumour immune cell infiltration, and biomarker analysis. Results: At data cut-off, 22 subjects have been enrolled in the study. The median age is 75.5 years (50-82). Thirteen of 22 subjects (59.1%) are GCB sub-type, 8 subjects (36.4%) are non-GCB and 1 subject (4.5%) has primary cutaneous DLBCL, leg type. The median number of prior therapies is 2 (1-7), with 4 subjects having previously undergone ASCT and 5 subjects with transformed disease. Of the 22 enrolled subjects, 8 are not evaluable per protocol for clinical efficacy due to early disease progression. Four subjects are active on treatment, 3 of which have not yet reached the first time point for assessment. Clinical outcome was analyzed for the Full Analysis Set (FAS) (n=19) and in the Per Protocol (PP) analysis (n=11). Of 11 subjects in the PP, 7 subjects (63.6%) have achieved an objective response, meeting the study's primary endpoint; 3 subjects (27.3%) with a CR and 4 subjects (36.4%) with a PR. Three subjects (27.3%) achieved SD and thus clinical benefit was demonstrated in 10/11 (90.9%) of evaluable subjects. Two subjects (18.2%) have completed the 1 year treatment period, 8 subjects (72.7%) discontinued treatment due to disease progression, and 1 subject (9.2%) discontinued treatment due to an unrelated Adverse Event (AE). Including the entire FAS, the objective response rate was 7/19 (36.8%). This treatment combination is well-tolerated, only 11% of Treatment Related AEs (TRAEs) were assessed as Grade 3 or higher. The majority of the Grade 1 and 2 TRAEs were Injection Site Reactions (ISRs) related to DPX-Survivac. Ten serious AEs were reported, of which 3 were considered related to study treatment. No subjects have discontinued study treatment due to a TRAE. Analyses of peripheral blood T cell responses to survivin by ELISpot assay shows that 7/7 subjects who achieved an objective response have survivin-specific T cell response. One subject with PD also showed a survivin-specific T cell response, supporting the mechanism of action and the role of DPX-Survivac in anti-tumor activity. Summary: DPX-Survivac and low dose CPA in combination with pembrolizumab, demonstrates promising clinical activity in recurrent/refractory DLBCL with 10/11 (90.9%) of evaluable subjects deriving clinical benefit with minimal toxicity. The primary endpoint of this study has been reached with 7/11 (63.6%) of evaluable subjects achieving an objective response warranting further exploration of DPX-Survivac in this population. Enrollment is continuing to further define the patient population most likely to benefit from this well-tolerated therapy. Figure 1 Disclosures Bence-Bruckler: Merck: Membership on an entity's Board of Directors or advisory committees. Forward:Seattle Genetics: Research Funding; IMV: Research Funding; Merck: Research Funding; Astellas: Research Funding; Servier: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; IMV: Membership on an entity's Board of Directors or advisory committees; Calgene: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AstraZeneca: Membership on an entity's Board of Directors or advisory committees. Stewart:Roche: Honoraria; Janssen: Honoraria; Abbvie: Honoraria; Gilead: Honoraria; Celgene: Honoraria; Amgen: Honoraria; Sandoz: Honoraria; Novartis: Honoraria; AstraZeneca: Honoraria; Teva: Honoraria. Bramhecha:IMV Inc.: Current Employment. Conlon:IMV Inc.: Current Employment. OffLabel Disclosure: Keytruda (pembrolizumab). Indicated for use in melanoma, nonÃÆ'Ã'¢Ã¢ââ'¬Å¡Ã¢â€šâ'¬ÃƒÂ¢Ã¢â€šâ'¬Ã…“small cell lung cancer (NSCLC), head and neck squamous cell cancer (HNSCC), classical Hodgkin lymphoma (cHL), primary mediastinal B-cell lymphoma (PMBCL), urothelial carcinoma, microsatellite instability-high (MSI-H) or a mismatch repair deficient (dMMR) solid tumor, gastric or gastroesophageal junction (GEJ) adenocarcinoma, squamous cell carcinoma of the esophagus, cervical cancer, hepatocellular carcinoma, Merkel cell carcinoma (MCC), and renal cell carcinoma (RCC).

Introduction: Historically, CNS lymphomas have been associated with a very poor prognosis High-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) has been investigated in patients with primary central nervous system lymphoma (PCNSL) and secondary central nervous system lymphoma (SCNSL) with promising results in small recent small prospective phase 1/2 results and retrospective series. We hypothesized that the use of R-BuMelTt (rituximab, busulfan, melphalan, thiotepa) conditioning regimen with ASCT regimen will be effective for both patients with PCNSL and SCNSL as used in previously reported promising data by Oh et al 2016 for patients with SCNSL with higher remission and survival rates. Patients and Methods: A retrospective analysis was performed of 6 consecutive patients who had undergone R-BuMelTt conditioning regimen with ASCT for 3 patients with PCNSL and 3 patients with SCNSL from December 2017 to March 2020. The median age of this patient population was 62 years at the time of ASCT. The induction chemotherapy regimen used for patients with SCNSL was R-CHOMP except one patient who received DHAP, and for patients with PCNSL MATRix regimen was used. The median duration of chemotherapy cycles was 4, and all of them had achieved remission prior to transplant based on PET/CT scan/MRI scan. All patients were planned to undergo ASCT using the Conditioning Regimen of Rituximab 375 mg/m2 on Day-7, Thiotepa 250 mg/m2 on Day-6,-5, Busulfan 3.2 mg/kg on Day-4,-3,-2 and Melphalan 100 mg/m2 on Day-1. Supportive cares measures were given at treating physician's discretion. Results: Patients received a median cell dose of 4.4x106 CD34+cells/kg (range: 2.5-5.7), had neutrophil engraftment at 11.5 days (range:9-13), platelet recovery was achieved on days 11,15 and 16 for three patients but was delayed at 27, 46, 89 days for 3 patients. Infectious complications were common with documented bacteremia in in 3 out of 6 patients, 2 patients with c. difficile infection and with significant platelet support due to thrombocytopenia. At a median follow up of 24.5 months (range: 6-30 months), 5 out of 6 patients had complete metabolic response on radiological imaging with PET/CT in conjunction with MRI head. One of the patients with SCNSL died after transplant due to CNS relapse 223 days post ASCT giving an overall survival of 66.6%. Amongst the 2 patients with SCNSL that survived there was no relapse after 30 month follow-up. None of the patients with PCNSL died or relapsed during or after transplant therefore having a 100% overall survival. Although this is a small retrospective study, our results are comparable to current literature. Toxicities included nausea/vomiting, diarrhea, mucositis with 5/6 patients requiring TPN. Also busulfan PK levels were not done. Conclusions: R-BuMelTt regimen can be used successfully as conditioning regimen for ASCT for patients with PCNSL and SCNSL, however with increased hematological toxicity, most notably delayed platelet engraftment. The rate of progression free and overall survival is promising with short median follow up of 24 months. Disclosures Lam: Janssen: Honoraria, Speakers Bureau; Roche: Honoraria, Speakers Bureau.

Patients with mantle cell lymphoma (MCL) have a particularly poor prognosis when treated with standard chemotherapy, with a median overall survival of only 3 years. These patients have therefore been considered for first-line treatment with more aggressive or experimental strategies, such as high-dose therapy (HDT) with autologous stem cell transplantation (ASCT). While high rates of clinical remission have been achieved with HDT/ASCT, this procedure alone is not believed to be curative and different treatment strategies are being developed to improve outcomes in this group of patients. Single-agent rituximab is active in both newly diagnosed and relapsed MCL and therefore the addition of rituximab to chemotherapy regimens and/or HDT/ASCT may enhance their efficacy. Outside the transplantation setting, rituximab plus chemotherapy has been shown to be highly active in MCL, and preliminary data from randomized trials suggest that the combination may yield superior results compared with chemotherapy alone. The addition of rituximab to transplantation protocols appears to be a very promising strategy for patients with MCL, given as an in vivo purge before HDT/ASCT and/or as posttransplant maintenance therapy. Two phase II clinical trials with rituximab given as an in vivo purge during stem cell mobilization and as posttransplant immunotherapy in patients with previously untreated MCL have generated very promising data. Rituximab is an important addition to cytotoxic therapy and with HDT/ASCT represents a highly active therapy that may be superior to conventional treatment or HDT/ASCT alone in MCL. Randomized prospective studies and longer follow-up are needed to determine whether these regimens can achieve longer survival or possibly cure in this disease.

Background: There is no current standard of care therapy for the management of patients with aggressive lymphomas in the relapsed or refractory (R/R) setting who are not candidates for intensive salvage chemotherapy and/or autologous stem cell transplant (ASCT). The combination of lomustine (CCNU), etoposide and prednisone (CEP) is an oral chemotherapeutic regimen that is modified from CCEP used in Hodgkin Lymphoma (CCNU, chlorambucil, etoposide and prednisone). CEP consists of alternating A & B cycles as follows (Figure 1): 'A' cycles contain lomustine 80 mg/m2 on day 1 as well as etoposide 100 mg/m2 and prednisone 100 mg on days 1-7. 'B' cycles contain only the etoposide and prednisone. Cycles are given every 21 days apart. To date there has been no published data on CEP's efficacy and tolerability in aggressive R/R lymphoma. In this study, we describe our institutional experience with CEP at the London Regional Cancer Program (LRCP) in London, Ontario for patients with R/R aggressive lymphomas unable to tolerate intensive chemotherapy. Methods: We conducted a retrospective review of patients who received CEP at LRCP between January 2014 and May 2018 for R/R aggressive lymphomas. The primary endpoint was overall response rate (ORR). Secondary endpoints included overall survival (OS), progression-free survival (PFS), and adverse effects related to CEP. Kaplan-Meier survival curves modeled PFS and OS. We also performed univariate and multivariate analyses to assess whether pre-specified variables (age, IPI score at diagnosis, LDH at time of treatment, and the number of prior lines of therapy) were independently associated with response to CEP (using linear regression) or progression-free survival (using the Cox proportional hazards model). IPI score (0-2 vs. 3-5) and the number of prior lines (1-2 vs. ≥ 3) were analyzed as binary variables due to the overall sample size. Results: 46 patients received CEP at LRCP during the study period. Diffuse large B-cell lymphoma was the most common diagnosis (70%) with Hodgkin lymphoma (6.5%) and peripheral T-cell lymphoma (6.5%) being the next most common. The median age of patients starting CEP was 76, with the median number of prior therapies being 2 (range 1-6). The primary outcome was ORR, which was 41% in our population, with a median time to response of 23 days. The median PFS was 2 months while the median OS was 4 months (Figure 2). The 2-year PFS and OS were both 8.7%. The median CEP treatment period was 1.5 full cycles while the longest CEP treatment period was 21 consecutive cycles. Univariate analysis revealed that lower IPI score (p=0.037) was significantly associated with ORR, while lower LDH (p=0.029) was significantly associated with PFS. Multivariate analyses revealed no factors associated with ORR, while lower LDH (p=0.017) and lower IPI (p=0.037) were associated with PFS. Toxicities were manageable with 48% with cytopenias of any grade and the most common grade 3-4 toxicity was febrile neutropenia in 13%. Conclusions: CEP is a safe, and convenient, all-oral palliative regimen for R/R aggressive lymphoma who are not eligible for intensive salvage chemotherapy or ASCT. The median OS in our population is comparable to pooled clinical trial and academic center data from non-transplant eligible patients with R/R DLBCL (Crump et al, Blood, 2017). Some patients even in spite of low performance statuses were able to tolerate many cycles of CEP with a long period of disease control, suggesting it is a reasonable treatment option for frail patients to balance disease control with an acceptable side-effect profile. Disclosures Lam: AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Other: Education Grant; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GSK: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees. Phua:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Teva: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda/Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; NovoNordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Octapharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bioverativ: Honoraria, Membership on an entity's Board of Directors or advisory committees; Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: 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.

It is estimated that 4-10% of patients with chronic lymphocytic leukemia (CLL) will develop autoimmune hemolytic anemia (AIHA) over the course of their disease. Ibrutinib has proven to be effective in treatment of relapsed, refractory, 17p deleted, and treatment naïve CLL. The effect of ibrutinib on AIHA in the context of CLL has not been established since patients with active hemolysis were excluded from major trials. In this abstract, we present a case series of patients that were actively hemolyzing at the start of ibrutinib therapy and in which their AIHA achieved prolonged response. Patient characteristics and laboratory data are shown in Table. Five patients (3 women, 2 men), median age 61 years (range 57 to 78), with CLL and active, uncontrolled AIHA at the time of ibrutinib initiation were identified. Uncontrolled AIHA was defined as anemia with evidence of hemolysis (at least two of the following: increased reticulocyte count, elevated lactate dehydrogenase, elevated indirect bilirubin, and reduced haptoglobin and a positive direct antiglobulin test (DAT)). Patients had a median hemoglobin of 70 g/L (range 69-96) prior to start of ibrutinib and 3 of them required transfusion support for symptomatic anemia. All patients were receiving prednisone for management of AIHA at the time of ibrutinib initiation and had been on it for a median of 10 days (range 9 - 25) without AIHA resolution. 1 patient received intravenous immunoglobulin concurrently. All patients had received at least one line of therapy for CLL in the past and 3 had experienced previous AIHA responsive to steroids. AIHA in 2 patients was related to previous fludarabine exposure but had responded to a prednisone tapering schedule and were off steroids by the time of the new AIHA flare. Median hemoglobin of 130 g/L (range 113-149) was reached at time of AIHA response. All 5 patients tolerated 420mg oral daily of ibrutinib therapy and AIHA was controlled in a median of 6.5 weeks (range 6-10). Discontinuation of steroids was achieved in all patients at a median of 10 weeks (range 6-17) without evidence of further hemolysis. All patients except one are receiving ongoing follow up and have been followed up for a median of 130 weeks (range 15-150) since ibrutinib start. Patients have not shown evidence of AIHA relapse and continue off AIHA treatment (prednisone). One patient required discontinuation of ibrutinib 6 months after starting due to neutropenia but there was no evidence of AIHA relapse in follow up. The patient has passed away from unrelated GI bleed 2 years after the initial AIHA event. This is the largest case series to our knowledge on the safe start of ibrutinib in CLL complicated by active AIHA. Hemolysis in all patients responded to a short prednisone taper with ibrutinib concurrently and obtained a sustained response at follow up without any flare ups or further AIHA treatment use. These cases suggest that it is safe to start ibrutinib during uncontrolled, active hemolysis in contrast to 2 previous case reports that suggested causal relationship between ibrutinib and onset of severe CLL-associated AIHA (Rider et al, 2015; Hodskins et al, 2014). As previously reported, AIHA occurrence or relapse once ibrutinib has been started is rare (Rogers et al, 2016). Disclosures No relevant conflicts of interest to declare.

Many believe that knowledge of anatomy is essential for performing clinical procedures; however, unlike their surgical counterparts, internal medicine (IM) programs rarely incorporate anatomy review into procedural teaching. This study tested the hypothesis that an educational intervention focused on teaching relevant surface and underlying anatomy would result in improved bone marrow procedure landmarking accuracy.This was a preintervention-postintervention prospective study on landmarking accuracy of consenting IM residents attending their mandatory academic half-day. The intervention included an interactive video and visualization exercise; the video was developed specifically to teach the relevant underlying anatomy and includes views of live volunteers, cadavers, and skeletons.Thirty-one IM residents participated. At pretest, 48% (15/31) of residents landmarked accurately. Inaccuracy of pretest landmarking varied widely (n = 16, mean 20.06 mm; standard deviation 30.03 mm). At posttest, 74% (23/31) of residents accurately performed the procedure. McNemar test revealed a nonsignificant trend toward increased performance at posttest (P = 0.076; unadjusted odds for discordant pairs 3; 95% confidence interval 0.97-9.3). The Wilcoxon signed rank test demonstrated a significant difference between pre- and posttest accuracy in the 16 residents who were inaccurate at pretest (P = 0.004). No association was detected between participant baseline characteristics and pretest accuracy.This study demonstrates that residents who were initially inaccurate were able to significantly improve their landmarking skills by interacting with an educational tool emphasizing the relation between the surface and underlying anatomy. Our results support the use of basic anatomy in teaching bone marrow procedures. Results also support the proper use of video as an effective means for incorporating anatomy teaching around procedural skills.