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FISH cytogenetics, TP53 sequencing, and IGHV mutational status are increasingly used as prognostic and predictive markers in chronic lymphocytic leukemia (CLL), particularly as components of the CLL International Prognostic Index (CLL-IPI) and in directing therapy with novel agents. However, testing outside of clinical trials is not routinely available in Canada. As a centralized CLL clinic at CancerCare Manitoba, we are the first Canadian province to evaluate clinical outcomes and survivorship over a long period of time, incorporating the impact of molecular testing and the CLL-IPI score. We performed a retrospective analysis on 1315 patients diagnosed between 1960 and 2018, followed over a 12-year period, where 411 patients had molecular testing and 233 patients had a known CLL-IPI score at the time of treatment. Overall, 40.3% (n = 530) of patients received treatment, and 47.5% (n = 252) of patients received multiple lines of therapy. High-risk FISH and CLL-IPI (4-10) were associated with higher mortality (HR 2.03, p = 0.001; HR 2.64, p = 0.002), consistent with other studies. Over time, there was an increase in the use of targeted agents in treated patients. The use of Bruton’s tyrosine kinase inhibitors improved survival in patients with unmutated IGHV and/or TP53 aberrations (HR 2.20, p = 0.001). The major cause of death in patients who received treatment was treatment/disease-related (32%, n = 42) and secondary malignancies (57%, n = 53) in those who were treatment-naïve. Our data demonstrate the importance of molecular testing in determining survivorship in CLL and underpinning the likely immune differences in outcomes for those treated for CLL.

Oncology pharmacists, pharmacy technicians and assistants are key members of the multidisciplinary health care team (MHT) caring for patients receiving immunotherapy with immune checkpoint inhibitors. The International Society of Oncology Pharmacy Practitioners (ISOPP) developed this position statement to provide guidance on the role of oncology pharmacy practitioners in caring for patients receiving immune checkpoint inhibitors. Four key recommendations were identified: 1) participation as an integrated, collaborative member of the MHT; 2) provision of education and training for patients, students, residents, fellows and other members of the MHT; 3) involvement in clinical governance to optimise the use of immune checkpoint inhibitors and 4) involvement in research and development in the field of immunotherapy. In summary, oncology pharmacy practitioners play essential roles within the MHT in caring for patients receiving immune checkpoint inhibitors.

Aims: Acute lymphoblastic leukemia (ALL) is an aggressive form of leukemia with a poor prognosis in adult patients. The addition of the monoclonal antibody rituximab to standard chemotherapy has been shown to improve survival in adults with ALL. However, it is unknown whether the addition of rituximab is cost-effective. The objective was to determine the economic impact of rituximab in addition to standard of care (SOC) chemotherapy vs SOC alone in newly-diagnosed Philadelphia chromosome-negative, CD20-positive, B-cell precursor ALL. Methods: A decision analytic model was constructed, based upon the Canadian healthcare system. It included the following health states over a lifetime horizon (max ≈60 years): event-free survival (EFS), relapsed/resistant disease, cure, and death. SOC was either hyper-CVAD or the Dana Farber Cancer Institute (DFCI) ALL consortium. EFS, overall survival, and serious adverse event (SAE) rates were derived from a large randomized controlled trial. Costs of the model included: first-line treatment and administration, disease management, second-line and third-line treatment and administration, palliative care, and SAE-related treatments. Inputs were sourced from provincial and national public data, the literature, and cancer agency input. Results: Quality-adjusted life-years (QALYs) increased by 2.20 QALYs with rituximab in addition to SOC. The resulting mean Incremental Cost-Effectiveness Ratio (ICER) was C$21,828/QALY. At a willingness-to-pay threshold of C$100,000/QALY, the probability of being cost-effective was 98%. Decision outcomes were robust to the probabilistic and deterministic sensitivity analyses, including the SOC backbone as either hyper-CVAD or DFCI. Limitations: The results of this analysis are limited by generalizability of the chemotherapy backbone to Canadian practice. Conclusions: For adults with ALL, rituximab in addition to SOC was found to be a cost-effective intervention, compared to SOC alone. The addition of rituximab is associated with increased life years and increased QALYs at a reasonable incremental cost.

Background:Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in North America with the majority of patients being over the age of 70 (Goede et al, 2014). CLL is a heterogeneous disease with some patients undergoing treatment at time of diagnosis, while others follow along a more indolent, asymptomatic course. When indicated, the choice of treatment is based on the patient's functional status, renal function and other comorbidities (Shanafelt, 2013). Previous studies have shown that unfit patients treated with Obinutuzumab plus Chlorambucil have shown prolongation of progression free survival and higher rates of complete response compared to other monoclonal based regimens (Goede et al, 2014). The aim of this study is to investigate the clinical use and uptake of Obinutuzumab in combination with Chlorambucil in a Canadian based population. Methods:All patients receiving Obinutuzumab were identified using the CLL CAISIS database. Then a retrospective chart review was conducted for patients approved for first-line antibody treatment with Obinutuzumab from January 1, 2014 to December 31, 2017. Data including patient characteristics, patterns of treatment, reported toxicities, response rates and survival data were collected and analyzed. This data was used to determine the overall safety and efficacy of this treatment regimen. Results: There were a total of 66 patients that met the inclusion criteria for this study. This cohort consisted of 54.5% males and 45.5% females, with a median age at diagnosis of 68 years (range: 46-94). Within this population 47 patients underwent florescence in situ hybridization testing, which identified 32 patients with chromosomal abnormalities. The immunoglobulin heavy chain variable region gene mutation was also tested in 41 patients, and identified 22 patients that were unmutated. At the time of treatment the median age was 73 (range: 55-98) with a median Cumulative Illness Rating Scale (CIRS) score of 8 (range: 3-15). Of the 66 patients who started treatment with Obinutuzumab, 50 patients (76%) achieved a partial response and 5 patients (8%) had no response. Of note, 21 patients (31.8%) discontinued treatment prior to completion of all six cycles due to cytopenias (4), other comorbidities (4), progression of CLL (2), decline in functional/mental status (2), patient request (2) and other (7). In regards to their treatment there was a high incidence of infusion related reactions (IRRs) on the first day of treatment, with 30 patients (45.5%) requiring intervention. There was a subset of 15 patients that had received low dose Chlorambucil prior to treatment with Obinutuzumab which resulted in a lower average lymphocyte count (38.1) and lower rate of IRRs (33%) compared to those with no prior Chlorambucil (average lymphocyte count: 66.5, rate of IRR: 42%). Due to toxicity and tolerability of Chlorambucil, dose reduction was observed in 37 patients (56%) throughout all six cycles of treatment. In the end, only 18 patients (27.3%) received all doses of Obinutuzumab and Chlorambucil while 37 patients (56%) received all doses of Obinutuzumab. Within the entire cohort, 12 patients have relapsed and 9 of these patients have required additional therapy. This relapse rate can be attributed to lack of response to Obinutuzumab (3), a 17p del (1), poor prognostic markers (5), and inadequate Obinutuzumab (1). Conclusion:In this current study, our results demonstrate that the majority of patients in this cohort were able to complete treatment with Obinutuzumab. Although our demographics were similar to previous studies, we found higher partial response rates (76%) likely due to differences in standards of practice, such as imaging studies after treatment. Disclosures Whiteside: Roche: Membership on an entity's Board of Directors or advisory committees, Other: teaching sessions. Dawe:AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Merck: Membership on an entity's Board of Directors or advisory committees. Johnston:Roche: Other: unrestricted grant received in the past; Abbvie: Other: unrestricted grant received in the past; Teva: Other: unrestricted grant received in the past; Gilead: Other: unrestricted grant received in the past; Janssen: Other: unrestricted grant received in the past. Banerji:Roche: Other: Unrestricted grant received in the past; Janssen: Other: Unrestricted grant received in the past; Abbvie: Other: Unrestricted grant received in the past; Gilead: Other: Unrestricted grant received in the past; Teva: Other: Unrestricted grant received in the past.

Abstract 1508 Background: Azacitidine (AZA) is an efficacious therapy for high risk Myelodysplastic Syndrome (MDS). In a randomized trial by Fenaux et al. patients were treated with a median of 9 cycles of AZA at 75mg/m2/day × 7 days every 28 days. Based on the published treatment regimen (Lancet Oncol 2009; 10: 223-32), the average cost of AZA is estimated to be $10,000 Canadian dollars per month. With a median of nine full dose cycles of AZA cost per patient is anticipated to be $90,000. In many health care systems, AZA has not been approved, due to financial constraints. Population based studies may provide a more realistic estimate of AZA drug utilization and cost. The province of Manitoba (population 1.2 million) offers a unique opportunity to perform population based studies, as provincial health and pharmacy services capture information regarding administration of parenteral drugs like AZA. Although AZA is not funded by the province, it was provided by the manufacturer on compassionate basis for any patient who met the approved criteria from April 2009 to 31 March 2010. Enrolled patients continued to receive the drug even after March 2010. The drug was administered at a single site. Methods: All patients enrolled during the period of compassionate use (April 2009-31 March 2010) who received one or more doses of AZA were prospectively followed for drug administration, response, toxicity and outcome. For this analysis, the last follow up was 31 July 2010. Results: Eleven eligible patients received at least one cycle of AZA. The diagnosis was MDS in 8, AML in remission with underlying MDS in 2 and CMML in 1. Four of eleven patients had therapy-related MDS and two patients were ECOG >2 at onset of therapy. A total of 42 cycles were given with a median of 3.0 (range 1–9) cycles per patient. There was a 25–50% dose reduction in 9 of 42 cycles (21%) due to cytopenias. Eleven of 42 cycles (26%) were complicated by febrile neutropenia, with 7 of these episodes requiring hospital admission. Reasons for discontinuing AZA were: (a) progressive cytopenia or transformation to AML in four (b) acceptance for allogeneic hematopoietic stem cell transplantation (HSCT) in three (c) severe sepsis during therapy in two (d) lack of objective response in one. Only one patient continues on AZA. Hematologic improvement and transfusion independence was seen in 5/11 and 3/11 patients respectively. There were two patients with bone marrow complete response (CR) in addition to hematologic improvement, one of whom underwent HSCT. The approximate cost of AZA in this cohort is $34,090 per patient. Conclusion: In this population based study, we demonstrate that many MDS patients are withdrawn from further treatment due to adverse effects or lack of early response, in contrast to patients participating in clinical trials. Despite receiving dose reductions and fewer total cycles of AZA, a comparable number of patients (45.5%) had objective responses. Our study suggests that the actual drug acquisition cost would be just over one third (38%) of the projected cost based on clinical trial data. Decisions to fund or deny expensive drugs should include data from population based studies. Disclosures: Kumar: Celgene: Membership on an entity's Board of Directors or advisory committees.