ALBERT

Description: Abstract 2475 Poster Board II-452 Introduction: Non-Hodgkin Lymphoma (NHL) is the fifth most common type of malignancy in Canada. The most common subtype of NHL is diffuse large B-cell lymphoma (DLBCL). Initial standard treatment for DLBCL includes combination immuno-chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). This regimen is typically administered every 21 days for a total of 6 cycles. Febrile neutropenia (FN) is a serious toxicity of lymphoma chemotherapy and patients with this condition must be treated aggressively as it could lead to complications such as prolonged hospitalization and death. Granulocyte-colony stimulating factors such as filgrastim and pegfilgrastim are efficacious in preventing FN, yet their cost-effectiveness has not been evaluated in the publicly funded Canadian healthcare system. Methods: A Markov model was constructed to evaluate the cost-effectiveness (cost-utility) of filgrastim and pegfilgrastim as primary prophylaxis versus no primary prophylaxis against FN in DLBCL patients receiving induction chemotherapy. Health states included in the model were hospitalization for FN, and receiving chemotherapy with no FN. It was assumed that patients in the no primary prophylaxis arm of the model who experienced a FN episode would receive secondary prophylaxis with filgrastim for all subsequent chemotherapy cycles. The time horizon of the model was 18 weeks, the time period over which the six cycles of chemotherapy are administered. The analysis was conducted from the hospital perspective. Costs are reported in 2009 Canadian dollars and outcomes in quality-adjusted life years (QALY). One-way sensitivity analyses were done on model parameters. A probabilistic sensitivity analysis was done to evaluate overall uncertainty in the model. Results: In the base case analysis costs associated with the no primary prophylaxis, filgrastim and pegfilgrastim interventions were $6044, $9450 and $15899, respectively. Quality-adjusted life years associated with the three interventions were 0.198, 0.200, and 0.202 respectively (over the 18-week model time horizon). The incremental cost-effectiveness ratio (ICER) of filgrastim compared to no primary prophylaxis was estimated to be $1.7 million (M)/QALY [95% confidence interval: -14M/QALY (dominated) to $15M/QALY]; for pegfilgrastim compared to filgrastim the ICER was estimated to be $4.4M/QALY [95% confidence interval: -25M/QALY (dominated) to $22.7M/QALY]. All one-way sensitivity analyses yielded ICERs of greater than $1M/QALY. Conclusions: The ICERs for filgrastim and pegfilgrastim when used as primary prophylaxis against FN in DLBCL patients receiving induction chemotherapy are well above the usually accepted cost-effectiveness threshold of $50,000/QALY. Disclosures: Mittmann: Amgen Canada: Unrestriced educational grant.

Description: The treatment of ARL is complicated by the numerous immuno-chemotherapy, antiretroviral, and prophylactic options available to lymphoma specialists. The optimal management in the era of combination antiretroviral therapy (cART) is unclear. We administered a survey instrument to determine physician preferences and perceptions in the management of ARL and to assess the variability in treatment in Canada. The survey was developed with items grouped into key domains of ARL management (physician demographics, attitudes, and treatment preferences) and piloted for content validity and clarity. The final questionnaire was administered to lymphoma physicians with valid contact information in the provinces of Ontario (ON; n=155) and British Columbia (BC; n=48). The Dillman Tailored Design Method was followed for multi-modality (internet and standard mail) survey administration. Of 196 physicians, 131 either responded by completing the questionnaire (n=117; 60% response rate) or declining to participate (n=14; 7%). Most responders were male (63%), white (70%), practicing in an academic setting (63%), and belonged to a median age group range of 41–50 years. The majority (98%) had a positive attitude towards the treatment of ARL, as measured by a previously validated 2-item attitude scale. However, barriers to adequate care were still identified; 84% of physicians agreed that uncontrolled human immunodeficiency virus infection represented a major barrier to ARL care and 54% agreed that a patient’s concurrent intravenous drug abuse impaired care. Most physicians recommended the concomitant use of cART in the care of their patients with ARL (n=72 of 109 responses; 66%). Similarly, a majority of respondents recommended CHOP-like regimens (cyclophosphamide, doxorubicin, vincristine, and prednisone; n=92 of 108 responses; 85%) to form the backbone of chemotherapy. The addition of the rituximab was preferred by 41% physicians but not by 40% others, with remaining respondents unsure of the agent’s role. In logistic regression analysis, use of rituximab was predicted only by location of practice (province), after adjusting for other potential predictors including physician age, race, gender, practice environment (academic vs. community), years of experience, ARL patient volume, and modality of survey response. Physicians from BC were much more likely to administer rituximab than ON practitioners (OR 44.5; 95% CI: 7.76–255.0, p

Description: Introduction: Sezary syndrome is a rare, aggressive and advanced stage of cutaneous T cell lymphoma where patients exhibit total body erythroderma and peripheral blood involvement. Patients can progress from preexisting mycoses fungoides or present de-novo. Historically median survival has been less than two years however with current combinations of skin directed and immunomodulatory therapy median survival has been documented up to 3–4 years, however randomized trials are lacking given the rarity of this disorder. We describe the outcomes 23 patients followed in our centre diagnosed with sezary syndrome based on peripheral blood involvement and erythroderma who have been treated primarily with combination skin and immunomodulatory therapy. Methods: A review of all patients diagnosed with sezary syndrome in our centre was conducted. Base line characteristics, survival, number and type of therapies as well as responses to treatments were recorded Results: 23 patients were identified. 11 male, 12 female, average age at diagnosis 64.7 yrs (range 47–85). Therapies included total skin electron beam (TSEB), PUVA, Interferon, oral retinoids, and extracorporeal photophoresis (ECP). 5 patients had received prior traditional chemotherapy including CHOP, chlorambucil and purine analogues with either no or transient responses. 19 patients received a combination of all 5 therapies. 19 patients received IFN, 13 TSEB, 21 PUVA, 18 ECP and 16 oral retinoids. 7 patients received 3 or fewer therapies (3 in process of escalating therapy, 1 CR to TSEB, 3 pts refused multiagent therapy as elderly and stable on PUVA +/− retinoids). 6 patients achieved a durable complete remission while on therapy (4 received IFN/TSEB/PUVA/ECP, 1 IFN/PUVA/ECP, 1 TSEB alone), 3 patients had progressive disease, and the remainder either had partial responses or stable disease. Median follow-up was 44 months (range 9–127). Median survival of the entire cohort was 37 months (mean 52 months, range 6–108 months, 5 patients have been diagnosed in the last 12 months). There have been 5 deaths to date, median 43 months (range 33–101) from the time of diagnosis. Cause of death included 2 cardiac, 1 renal, 1 infection, and 1 progressive disease. There was no correlation between survival and LDH at presentation, sezary cell count or number of therapies. There was a modest correlation between survival and age at diagnosis (R2=0.1263). Patients who received TSEB had an average of 57 months survival vs. 33.5 months than those who did not, however this was not statistically significant. Reasons not to receive TSEB included 5 patient refusal, 3 still escalating therapy, 2 had adequate response to other therapies. Patients who achieved a CR to therapy had a median survival of 63 months (average 65 months) vs. those who did not achieve a CR had a median survival of 22 months (average 65 months). Conclusions: Patients receiving combination immunotherapy and skin based treatments for sezary syndrome appear to be living longer than historical series. Given the small number of this cohort it was not possible to statistically determine variables predictive of prolonged survival, however patients who received TSEB and or achieved a CR to treatment had median survival of approximately 5 years. The majority of patients received maintenance immunotherapy to sustain disease control.

Description: Hodgkin lymphoma (HL) occurs in HIV-infected individuals more frequently than in the HIV-negative population and the incidence is rising. Patients (pts) with non-Hodgkin’s lymphoma in HIV appear to have improved outcomes if they receive HAART with chemotherapy (CT). ABVD is standard CT for HL and is frequently administered with HAART in pts with HIV-HL. However, some components of the ABVD regimen may interact with antiretroviral (ARV) medications to alter metabolism and increase toxicity. In particular, vinblastine (VBL) is metabolized by CYP3A4 and protease inhibitors, particularly ritonavir (RTV), appear to inhibit this cytochrome potentially leading to higher VBL exposure. Little definitive information is available regarding how interactions might affect clinical outcome. We conducted a retrospective review of 36 pts with HIV-related HL to identify the frequency of neurotoxicity (NT), hematologic toxicity (HT), and lung toxicity (LT), to identify risk factors for severe (grade III–IV) toxicity, and to determine its clinical significance. Clinical data were collected from the CFE database and by chart review from 3 centers. The median age at HL diagnosis (dx) was 41 (range 29–66) years and 34 (94%) were male. HL was advanced stage in 28 (78%). Hasenclever score could be calculated in 23 pts and was 0–4 and ≥5 in 15 and 8 pts respectively. ECOG PS was 0–1 in 13 and ≥2 in 8 (n=21). HIV risk factor was: sexual, n=21 and other, n=5 (n=26). Median CD4 count at HL dx was 210 (2–660) cells/ul (n=31). Median HIV viral load (VL) was undetectable (

Description: Introduction: Nearly one in five cancer survivors report limitations in ability to work following diagnosis, with poor work-related outcomes particularly noted in the hematologic cancers. Although much is known about the efficacy, toxicity and direct costs of treatment for follicular lymphoma, there is no data assessing the impact of this diagnosis on productivity of affected individuals. Methods: We conducted a consecutive cross-sectional study of patients attending a malignant hematology clinic at a large multi-disciplinary cancer centre. Patients with a diagnosis of FL or other indolent NHL were asked to complete questionnaires assessing demographics, health status (EQ-5D), and work productivity and activity impairment (WPAI questionnaire). Results: Eighty-four patients completed the survey study (〉95% response rate). Mean age was 58.7 (+/−13.8 SD) and 55% were male. Diagnoses included FL (55%), CLL (25%), and other indolent NHL (20%). The majority of patients presented in advanced stage (stage III–IV; 65%) and had received some therapy, although 29% were still being observed without having received therapy by the time of survey administration. The median disclosed income was $40,000–$59,000; 76% had pursued post-secondary education. Over 61% were working full-time prior to diagnosis while 14% were retired. Patients reported a minimal impact on their work productivity (1.9+/−3.2 on a scale of 0 to 10; 0=no effect and 10=complete impairment of activity) and on their daily activities (2.4+/−3.1) attributable to their cancer diagnosis. However, following diagnosis of NHL (and at the time of survey completion), only 33% were able to continue full-time work, 7% were working part-time, 10% required disability, and 37% were retired. Of those still working, a mean of 2.1 days (+/−6.9) were missed due to illness in the preceding 4 weeks, with a mean of 16 days (+/−8.7) worked in that period. Only 6% received paid assistance, while 17% required unpaid care from a partner/spouse, relative, or friend. Unpaid caregivers missed a mean of 11.3 days (+/−16.2) of work and provided a mean of 9.8 days (+/−13.4) of care. There was a significant inverse correlation between daily activity scores (high values=complete impairment) and health status ratings (high values=excellent health status/utilities) ascertained by the EQ-5D instrument (Spearman correlation coefficient −0.69; p5) was predicted by poor self-rated health status (OR 32.1; 95% CI 5.9–174.2; p

Description: Background: Patients with relapsed or refractory aggressive B-cell lymphoma, or transformed indolent lymphoma can achieve long-term survival with high dose therapy and autologous stem cell transplant (HDT/ASCT), provided their disease is sensitive to salvage chemotherapy. Unfortunately, approximately 50% of patients are insensitive to standard salvage regimens. Objectives: This trial investigated whether adding Rituximab to ESHAP (etoposide, solumedrol, cytosine arabinoside, cisplatin) induction improved chemosensitivity. The primary outcome was overall response rate (CR + CRu + PR) to R-ESHAP. Secondary outcomes were toxicity, ability to undergo ASCT, progression free survival (PFS) and overall survival (OS). Methods: The protocol was approved by the local ethics review board and all patients provided informed consent. Eligible patients received ESHAP every 28 days with GCSF support until 〈 15% bone marrow involvement was achieved (2–4 cycles). Rituximab was given weekly x 8 weeks concurrent with the first 2 cycles of ESHAP. GCSF mobilized stems cells were collected on day 10–11 of cycle 1 or 2. Results: The trial was stopped early after the complete response (CR) rate at a planned interim analysis exceeded 40% (a pre-specified criteria for stopping the trial). Final results of 26 patients are presented. Median age was 55.5 years (range 42–64). Twelve patients had relapsed aggressive lymphoma, 2 had refractory disease and 12 had transformed indolent lymphoma. Twenty-two of 26 patients were stage III/IV. The overall response rate to R-ESHAP was 92% (95% CI 82% to 100%). Twelve patients (46%; 95% CI 27% to 65%) had a CR or unconfirmed CR. Grade 3–4 thrombocytopenia, neutropenia, and anemia occurred in 57%, 40%, and 15% of R-ESHAP cycles respectively. Grade 3–4 infections complicated 7% of cycles. Median follow-up was 17 months (range 2.9 to 43.2) from enrollment. Twenty-three of 26 patients (88%) were transplanted. Notable post-transplant toxicity included 5 cases of herpes zoster, 2 cases of bacterial pneumonia, 1 case of pulmonary aspergillosis, and 1 fatal case of pneumocystis carnii pneumonia (PCP). Three patients did not proceed to HDT/ASCT; 2 were refractory to R-ESHAP and 1 died of a myocardial infarction after induction chemotherapy but prior to ASCT. Fifteen of 23 patients who received ASCT remain in remission, 6 have relapsed. Seven patients have died, 4 of progressive disease, 1 of myocardial infarction, 1 of PCP, and 1 of accelerated Parkinson’s Disease. Median PFS and median OS have not yet been reached. Conclusions: In this single-arm, phase II study of relapsed or refractory aggressive B-cell lymphoma and transformed indolent B-cell lymphoma, R-ESHAP induction therapy resulted in a very high ORR (92%) and enabled a large percentage of patients (88%) to proceed to HDT/ASCT. Toxicity of the R-ESHAP regimen was acceptable, and its efficacy compared favorably with other salvage regimens reported in the literature, including R-ICE.

Description: Abstract 1916 Poster Board I-939 Introduction: Since the introduction of combination antiretroviral therapy (cART), the incidence rates of non-Hodgkin's lymphoma (NHL) and primary central nervous system lymphoma (PCNSL) have declined; however, less is known about the rates of other hematologic malignancies such as Hodgkin lymphoma (HL) and multiple myeloma (MM). We aimed to study changes in the incidence and outcomes of hematologic malignancies (HMs) in the pre- and post-cART eras. Methods: A retrospective analysis of The Ontario HIV Treatment Network Cohort Study (OCS) was performed. The OCS is an ongoing prospective study of HIV-infected adults from 11 sites throughout Ontario, Canada. Incidence rates of HMs were calculated for the pre- (

Description: Abstract 3816 Background: The timely publication of cancer cost-effectiveness analyses (CEA) is essential to inform decisions regarding new drug adoption by relevant policy makers and stakeholders. This study examined the publication pattern and quality of CEA presented in the annual meetings of the American Society of Hematology (ASH). Methods: ASH abstracts from 1997 to 2007 were reviewed. Abstracts with a malignant focus and that reported primary outcomes of incremental cost per life-year-gained or quality-adjusted-life-year (QALY) were included. Data including ICER (adjusted to USD) and author affiliation to the pharmaceutical industry was extracted. Quality indicators associated with well-performed CEAs were derived from the literature (Weinstein MC et al., JAMA 1996;276:1253-1258) and used to determine abstract quality. A search for subsequent publication of the abstract findings was conducted using Medline. The primary outcome of time-to-publication was determined using Kaplan-Meier statistics. Predictor variables were tested using the log-rank statistic. Results: 29 abstracts met inclusion criteria. Only 13 were published (overall rate of 44.8%). The actuarial 1 and 3 year publication rates were 24.1% and 41.4% respectively (see figure). All but 1 abstract presented at ASH had an ICER less than $100 000/QALY (median $33 000/QALY) with 55.2% disclosing author affiliation to the pharmaceutical industry. Specific to abstracts published after 2001, when ASH instituted a policy of disclosure reporting, the proportion of abstracts reporting pharmaceutical affiliation was 72.7%. No variable or quality indicator predicted for time-to-publication though there was a trend for abstracts reporting dominant ICERs to yield more timely publications (p = 0.075). In terms of quality indicators, the reporting of a societal perspective, lifetime horizon, or a sensitivity analysis was noted in only 37.9%, 24.1% and 62.1% of abstracts, respectively. Conclusions: The publication rate of CEA abstracts from ASH was low and not timely for open discussion among stakeholders. Although there was no direct evidence of bias in abstracts selected for presentation, most reported highly favorable ICERs and consistent author affiliation with the pharmaceutical industry. Overall, the quality of abstracts appeared suboptimal. Disclosures: No relevant conflicts of interest to declare.

Description: Background: In the AZA-001 trial, azacitidine (AZA) altered the natural history of patients with higher-risk MDS (Fenaux et al., Lancet 2009) by significantly improving overall survival compared to conventional care regimens (24.5 months versus 15.0 months). Once approved for drug reimbursement by the provincial health ministry, Cancer Care Ontario (CCO) mandated that all eligible patients be enrolled in a prospective registry to ensure compliance with eligibility criteria and schedules of drug administration. Baseline characteristics were recorded and treatment response were to be submitted every 6 cycles of treatment. Our objectives were to audit this clinical program for results after 6 years and identify the prognostic markers for survival in a homogenous higher-risk MDS/low blast count AML patient population. Methods: Only higher-risk MDS patients (intermediate-2, high) as defined by the International Prognostic Scoring System (IPSS) and low blast count AML (20-30% blasts) treated with AZA in Ontario, Canada from June 1, 2010 to March 2, 2016 were eligible and included. Our primary outcome was overall survival (OS) from date of first AZA treatment. Our secondary outcomes were overall response rates and the predictors of OS including administration schedules, centre size or type (regional cancer versus community). Univariate and multivariable Cox proportional hazard model were used to determine the predictors of OS. Hazard ratios and generalized R2 (higher the R2, stronger association with OS) were also calculated. Results: 825 higher-risk MDS and 276 low blast count AML were included (n = 1101 total). Median age was 74 years (range 19 to 99), 65.2% were male and the IPSS scores were intermediate-2 (64.3%) and high-risk (35.7%). Sixty-six percent of patients were transfusion dependent (TD) at time of AZA initiation and 15.5% had received previous chemotherapy. By dosing schedule, 24.7% received AZA for 7 consecutive days (7d), 12.4% for 6 consecutive days (6d) and 62.9% by the 5-2-2 schedule. Overall, the median number of cycles received was 6 (range 1 to 67) and 8 (range 6 to 14) when restricted to the 692 (63%) patients who received at least 4 cycles of treatment. Dose reductions were seen in 33.3% of patients (mean 11.1 mg/m2 in those with reductions) and were more common over time (negative slope 0.178; p 〈 .0001). Of those with repeat bone marrow (n = 293) best response was complete response (CR) in 16.7% and partial response (PR) in 10.6%. Of those without CR/PR/progressive disease on bone marrow (n = 814), 20.4% experienced hematologic improvement including those with marrow CR and marrow stable disease. The actuarial median survival was 11.6 months (95% CI 10.7- 12.4) with a significantly longer OS for MDS compared with low blast count AML (12.4 months vs. 9.6 months; p = .0002) and 16.7 months (95% CI 15.2-18.1) for those receiving at least 4 cycles. There was no difference in OS between the 3 dosing schedules (11.7 months (7d) vs. 10.2 months (6d) vs. 12.0 months (5-2-2); p = .87; figure 1A), regional cancer centre vs. community (11.3 months vs. 11.7 months; p = .19; figure 1B) or by centre volume (11.4 months 〈 50 patients vs. 11.6 months 〉 50 patients; p = .38; figure 1C). On univariate analysis, the following were predictive of OS: blast percentage, number of cytopenias, karyotype, IPSS, WHO classification, TD, greater transfusion burden and secondary MDS. The multivariate model with the highest R2 (13.5%) included blast percentage (p 〈 .0001), karyotype (p 〈 .0001), cytopenias (p = .038), TD (p 〈 .0001) and secondary MDS (p = .0006) as summarized in the table below. Conclusions: In our large real world evaluation of AZA use in higher-risk MDS/low blast count AML, we validated the expected overall response rates to AZA but demonstrated a lower than expected OS compared to the AZA-001 trial. Reassuringly, survival did not differ by dosing schedules, centre volumes or center type (regional cancer vs. community). OS was higher in the 2/3 of patients who received at least 4 cycles of treatment, reinforcing the necessity of sustained administration until therapeutic benefits are realized. This represents the largest real world evaluation of AZA in higher-risk MDS/low blast count AML and additional analyses are underway. Table Table. Figure 1 Figure 1. Disclosures Mozessohn: Celgene: Honoraria. Buckstein:Celgene: Honoraria, Research Funding; Novartis: Honoraria.

Description: Background: G-CSF is commonly administered to patients with advanced-stage Hodgkin Lymphoma (HL) with severe neutropenia during therapy, although such an approach does not appear to provide a survival benefit. Although the therapy may reduce episodes of febrile neutropenia, any benefit might be offset by increased costs and the potential for increased bleomycin lung toxicity with G-CSF exposure, suggested in prior studies (Martin et al., JCO 2005). As an alternative to secondary prophylaxis, single institution studies have suggested that ABVD chemotherapy can be administered without G-CSF support, treatment delays, or dose reductions. The relative costs and benefits of such an approach compared to routine use of G-CSF is unknown. Methods: We constructed a Markov decision-analytic model to compare the strategy of secondary prophylaxis with G-CSF to a strategy of "no G-CSF" in response to therapy-related severe neutropenia for a cohort of 40 year-old patients with clinical stage IIB to IV HL treated with 8 cycles of ABVD. A 2-year time horizon was simulated. Baseline probability estimates and utilities were derived from a systematic review of relevant published studies. Direct medical costs were obtained from publicly available administrative databases or from the literature and applied to the health states. All costs and benefits were discounted by 3%. A Canadian public health payer's perspective was considered and costs were presented in 2013 Canadian dollars. Key variables were subjected to sensitivity analyses. Results: The quality-adjusted life years (QALYs) attained with the G-CSF and "no G-CSF" strategies were 1.403 and 1.416, respectively, for a net expected benefit of 0.013 QALYs associated with omitting G-CSF. Costs for the strategies with and without G-CSF were $38,971 and $33,982, respectively, with a cost savings of $4,989 when G-CSF is omitted. In the base case analysis, the "no G-CSF" strategy was associated with both cost savings and improved quality-adjusted outcomes compared to secondary prophylaxis; therefore, the "no G-CSF" approach was dominant. This analysis was robust to one-way sensitivity analyses involving all key variables; the "no-GCSF" strategy remained dominant even when the cost of G-CSF was zero (Figure 1). In probabilistic sensitivity analysis (1000 simulations), the "no-G-CSF" strategy remained dominant in all pairwise simulations compared to an approach with G-CSF for secondary prophylaxis (Figure 2). Conclusions: For patients with severe neutropenia during ABVD chemotherapy for advanced-stage HL, a strategy without G-CSF support, treatment delay or dose reduction is associated with improved quality-adjusted outcomes and cost savings and is the preferred approach. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.