Tom Baker Cancer Centre Research Articles

Long-Term Follow-Up of Non-Paraneoplastic Autoimmune Encephalitis: A Canadian Single-Center Experience

ABSTRACT: Background: Autoimmune encephalidities (AIE) are becoming an increasingly recognized cause of encephalitis. While diagnosis and acute management are well described, information on long-term management and outcomes is limited. Given this, we reviewed 5 years of AIE patients, reporting on chronic management, relapse incidence and possible relapse predictors. Methods: We performed a chart review of all patients with non-paraneoplastic AIE presenting to Calgary Neuro-Immunology Clinic and Tom Baker Cancer Centre between 2015 and 2020. Severity of relapse was determined using the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). Variables were assessed with descriptive analysis and/or t-test. Results: Patients were followed for a mean of 38.2 months. Outcome data were assessable in 37/38 patients. Relapse rate ranged from 0% (GFAP) to 67% (NMDA), with a mean of 46%. Most relapses (76%) occurred within 3 years. Time to treatment initiation at relapse was significantly shorter than initial presentation (p = 0.0015), and patients had less severe relapses compared to initial presentation (CASE score 5.18 vs 6.53; p = 0.040). Use of chronic immunotherapy did not appear to impact overall relapse risk, although patients on any immunotherapy at relapse had milder relapses based on ΔCASE (p = 0.0035). Conclusion: Relapse was not uncommon (46%) for various AIE subtypes in our cohort, particularly within the first 3 years. Our data enforce the importance of long-term follow-up, which in our study allowed for earlier treatment and less severe relapses compared to initial presentation, as well as the need to further explore which patients would benefit from chronic immunotherapy.

The Presence of Somatic Mutation in Donor Does Not Affect Long-Term Outcomes in 339 Patients Following Allogeneic Hematopoietic Stem Cell Transplantation Using Uniform Fludarabine/Busulfan Myeloablative Conditioning and Cyclosporine/Methotrexate and ATG Gvhd Prophylaxis

Introduction: Clonal hematopoiesis with indeterminate potential (CHIP) constitutes a part of the biological aging process and comprises the acquisition of somatic mutations in hematopoietic stem cells (HSCs). In the context of allogeneic hematopoietic stem cell transplantation (HCT), the potential transfer of CHIP from donor to recipient may raise concerns on HCT-related complications. There are contradictory data on donor CHIP's impact on long-term transplant outcomes using very diverse conditioning regimen as well as various graft-versus-host disease (GVHD) prophylaxis. This study aims to evaluate the impact of donor CHIP on allogeneic HCT outcomes in a cohort of the patients transplanted using a uniform, myeloablative intensity conditioning of Fludarabine-Busulfan (4 days) as well as Cyclosporine/Methotrexate with 4.5 mg/kg rabbit antithymocyte globulin (ATG) over 3 days for GVHD prophylaxis. Patients and methods: Peripheral blood samples were obtained from recipients and their corresponding donors who underwent allogeneic HCT at Tom Baker Cancer Centre, Calgary, Canada. Samples were archived from 339 patients and 255 donors prior to HCT, and additional patient sampling was done on day 28 (D28), day 56 (D56), or day 84 post allogeneic HCT (D84). As a result, paired recipient-donor samples were available for 255 HCTs. This study was approved by the institutional review boards of Princess Margaret Cancer Centre, Toronto, and Tom Baker Cancer Centre, Calgary. For the detection of CHIP, we have applied a bar-coded error-corrected sequencing protocol, a single-molecule molecular inversion probe capture protocol (NAR Genom Bioinform, 2022), which was performed at Wiesmann Institute of Science (Rehovot, Israel). We designed probes targeting 34 genes covering CHIP mutations along with other AML related mutations. Bar-coded NGS library was generated and processed. All statistical analyses were performed using R statistical software 3.5.0 and EZR version 1.41. Results: Sixty-seven clonal mutations in 56 recipients (18.2%) and 22 clonal mutations in 18 donors (7.1%) were detected prior to HCT. For recipients, TET2, JAK2, RUNX1, PPM1D, and DNMT3A were detected in at least 2 patients or more. For donors, the most frequently mutated gene was TET2 (3.1%), and the seconds were DNMT3A and PTPN11 (1.2% for both). Baseline characteristics of 255 patient-donor pairs did not show any difference between D-CHIP and no D-CHIP groups except donor age. Donor CHIP status was distributed evenly throughout most of the demographics of recipients, type of disease, pre-transplant status, and transplant procedure. Most of the pts received peripheral blood stem cells (97%). With a median follow up duration 6.02 years, the 5-year OS rates tend to be higher in no D-CHIP group than D-CHIP group (63.1% vs 42.8%) with a HR of 1.73 (95% CI [0.90-3.35]), although it was not statistically significant (p=0.096). The cumulative incidence of relapse for both groups were not different in 5 years (28.1% vs. 28.4%, p=0.849). The cumulative incidence of NRM within 5 years in D-CHIP group was slightly higher than no D-CHIP group (28.4% vs 17.5%), but it was not statistically significant (p=0.250). Neutrophil engraftment by day 28 was 99.1% vs. 100%, without statistical difference between the two groups (p=0.785). The cumulative incidence of grade II-IV acute GVHD within day+100 seemed to be higher in D-CHIP group compared to no D-CHIP group, but it was not statistically significant (24.8% vs. 34.5%, p=0.148; Figure A). In terms of chronic GVHD, cumulative incidence of moderate to severe GVHD was significantly higher in 5 years after transplant (29.4% vs. 58.8%; HR 2.55 [1.331-4.96], p=0.006; Figure B). Even when we set the cut off level of donor CHIP positivity up to >1% or >10%, the association between donor CHIP and risk of chronic GVHD remained significant. The impact of donor CHIP on the cumulative incidence of moderate to severe GVHD was confirmed in multivariate analysis (HR 2.3 [1.3-4.1], p=0.003). Other factors associated with moderate to severe chronic GVHD were previous history of grade II-IV acute GVHD (p=0.008) and donor type (p=0.054). Conclusion: Under clinical setting of uniform conditioning regimen and GVHD prophylaxis incorporating ATG (4.5mg/kg), donor CHIP was found to be associated with higher risk of moderate to severe chronic GVHD, while it does not affect other allogeneic HCT outcomes.

P.027 Autoimmune encephalitis: modifiable and non-modifiable predictors of relapse

Background: Approximately 25% of encephalitis cases in North America are autoimmune (AIE). For most forms of AIE, it is unclear which patients have the highest relapse risk and whether standard treatments reduce this risk. Our objective was to determine the overall risk of relapse and whether chronic immunosuppressive therapy modifies that risk. Methods: We performed a chart review consisting of all patients with AIE presenting to the Calgary Neuro-Immunology Clinic and Tom Baker Cancer Centre between 2015 and 2020. Predictors of relapse were determined with use of t-test. Results: Outcome data was assessable in 39 patients, 17/39 (44%) patients relapsed, and most relapses (76%) occurred within 3 years. Patients not on any immunosuppression at the time of relapse had a greater increase in CASE score, a proxy for presentation severity, at relapse compared to those on immunosuppression (p=0.0035). Conclusions: The risk of relapse in AIE is high (44%). Immunosuppression at the time of relapse, which may occur up to 3 years after initial presentation, lessens the relapse severity, although it remains unclear if it can reliably prevent relapses. Our data enforces the importance of long-term follow up and that ongoing immunosuppression may be helpful, particularly in the first 3 years after initial presentation.

Real-World Outcomes of Consolidative Autotransplant for High-Risk Large B-Cell Lymphoma

Background: Although there have been significant recent advances in the treatment of relapsed/refractory (r/r) large B-cell lymphoma (LBCL), there remains a substantial unmet need to optimize the frontline management of high-risk LBCL. Patients with high International Prognostic Index (IPI) scores 4-5 have particularly poor progression-free survival (PFS) rates of ~50% with R-CHOP, and 2-year PFS may be as low as 10-25% for patients with positive interim PET scans. In the phase III DLCL04 and SWOG-9704 trials, the use of upfront consolidative autologous stem cell transplantation (ASCT) after R-CHOP resulted in significant improvements in PFS, with the latter study also demonstrating a significant improvement in overall survival (OS) in the age-adjusted high IPI subgroup. Furthermore, the GAINED trial demonstrated favorable outcomes using an interim PET-adapted strategy, where consolidative ASCT appeared to overcome the poor prognostic impact of a positive interim PET. However, there is only limited and conflicting data from prospective or retrospective studies concerning ASCT consolidation for the highest risk patients with LBCL and IPI score 4-5, particularly those with positive interim PET scans. Methods: This retrospective, multicenter study included consecutive patients with newly diagnosed LBCL and high IPI score 4-5 who received consolidative ASCT as a planned part of first-line therapy at the Tom Baker Cancer Centre and Cross Cancer Institute in Alberta, Canada. Patients were excluded if they had primary central nervous system (CNS) lymphoma, previously treated indolent B-cell lymphoma, or underwent ASCT for r/r LBCL. PFS, OS, and disease-specific survival (DSS) were determined using the Kaplan-Meier method. Results: We included 114 patients with median age 60 years (range 18-73) and median follow-up time 5.6 years. High-risk features at diagnosis included IPI score 4 in 81 (71%), IPI score 5 in 33 (29%), stage IV in 112 (98%), >1 extranodal site in 109 (96%), non-GCB cell of origin by Hans’ algorithm in 32 (28%), double-hit lymphoma in 26 (23%), and secondary CNS involvement in 15 (13%). The most common induction regimen was R-CHOP (n=102) and 25 (22%) patients received 1-3 cycles, 71 (62%) received 4 cycles, and 18 (16%) received 5-6 cycles of induction. Rituximab with dose-intensive cyclophosphamide, etoposide, and cisplatin (R-DICEP) was frequently used (n=69) to intensify induction and for peripheral blood stem cell mobilization. Interim PET was performed during induction for 45 patients and was positive (Deauville 4-5) in 24 (53%) and negative (Deauville 1-3) in 21 (47%). Pre-ASCT disease status was complete response (CR) in 68 (60%), partial response (PR) in 43 (38%), and unknown in 3 (3%) patients. The most common ASCT conditioning regimens were BEAM in 41 (36%), BuMel in 39 (34%), and TBM in 13 (11%) patients. At 2 years, PFS was 82% (95% CI 74-88%), OS was 86% (95% CI 78-91%), and DSS was 87% (95% CI 79-92%). At 5 years, PFS was 72% (95% CI 62-80%), OS was 74% (95% CI 64-81%), and DSS was 80% (95% CI 71-87%). Relapse occurred in 21 (18%) patients at median 284 days (range 168-2229) after ASCT. There was 1 (1%) death due to early transplant-related infection and 3 (3%) late deaths from pulmonary fibrosis and therapy-related myeloid neoplasms. There were no significant differences in DSS for patients with versus without CNS involvement (77% vs. 80%, p=0.62), double-hit lymphoma versus DLBCL NOS (85% vs. 78%, p=0.80), GCB versus non-GCB cell of origin (78% vs. 80%, p=0.89) and positive versus negative interim PET (83% vs. 74%, p=0.51). Discussion: In this study of 114 selected patients with high-risk LBCL with IPI score 4-5, consolidative ASCT was associated with excellent outcomes with long-term disease-specific survival in 80%. Importantly, the efficacy of consolidative ASCT appeared to be independent of adverse prognostic factors including CNS involvement, double-hit status, non-GCB cell of origin, and interim PET positivity. The results of our study are consistent with those of previous clinical trials and provide real-world evidence confirming that consolidative ASCT can be considered a reasonable treatment option for eligible patients with high-risk LBCL. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

EP06.01-003 Impact of COVID-19 on Lung Cancer Patients; The Patients’ Perspective

EP06.01-003 Impact of COVID-19 on Lung Cancer Patients; The Patients’ Perspective

P.026 Autoimmune encephalitis: modifiable and non-modifiable predictors of relapse

Background: Approximately 25% of encephalitis cases in North America are immune mediated. For most forms of autoimmune encephalitis (AIE), risk of relapse is unclear and little evidence exists to guide which patients have the highest risk and whether standard treatments reduce this risk. Our objective was to determine the factors associated with AIE relapse. Methods: We performed a chart review consisting of patients with AIE presenting to the Calgary Neuro-Immunology Clinic and Tom Baker Cancer Centre between 2015 and 2020. Predictors of relapse were determined with use of t-test. Results: Outcome data was assessable in 39/40 patients, 17/39 (44%) patients relapsed. Seropositive patients and those with abnormal CSF were more likely to relapse, although neither reached statistical significance (p=0.12, 0.059). Patients with longer duration of steroid and steroid sparing treatment prior to relapse, and those on steroids at the time of relapse, had milder relapses (p=0.024, 0.026, 0.047). There was no difference in steroid or steroid sparing treatment use at 3, 6, and 12 months between groups. Conclusions: Risk of relapse in AIE is high (44%), with most relapses occurring in the first 3 years. Continuous immunosuppression lessens the severity of relapse, although our study did not confirm it reduced the occurrence of relapse.

Neuro-Oncology Rehabilitation Triage Clinic – Developing a Rehabilitation Decision Making Framework within the Cancer Care System

<h3>Research Objectives</h3> To determine triage criteria for neuro-oncology patients into exercise oncology versus other rehabilitation programming (i.e. physiotherapy, occupational therapy, and physiatry) based on a Rehabilitation Triage Clinic (RTC) assessment. It was hypothesized that the RTC assessments would determine effective referral into exercise or rehabilitation programs. <h3>Design</h3> The study was a prospective cohort study. <h3>Setting</h3> Patients were referred from the Tom Baker Cancer Center into the publicly funded Cancer Rehabilitation program. <h3>Participants</h3> Neuro-oncology patients >18 years and treated at the Tom Baker Cancer Centre in Calgary, Alberta, were referred into the RTC. <h3>Interventions</h3> The Rehabilitation Triage Clinic (RTC) was an assessment clinic designed to assess patients using a standard set of criteria, and determine appropriate referral for rehabilitation services. <h3>Main Outcome Measures</h3> A medical history, neurologic examination, Short Physical Performance Battery (SPPB), Eastern Cooperative Oncology Group (ECOG) status, and Karnofsky Performance Score (KPS) were used to determine triage. Triage criteria were based on pre-determined criteria including an ECOG <3, KPS >50, SPPB >10, and no new or unmanaged medical or neurological issues. Recruitment is ongoing. <h3>Results</h3> To date, 19 out of 32 eligible patients have been recruited, with an average of 57.2(±81.1) months since diagnosis. The mean SPPB score was 9.6 (±2.1, range 5 to 12), below cut-off, while the average KPS was 65 (±7.1, range 60-90), and ECOG score was 1.3 (±0.6, range 2 to 0), both above cut-off. Most patients were referred to multiple programs, including 2/19 patients to physiatry, 17/19 to physiotherapy, and 8/19 to occupational therapy. All 19 patients were referred to and have tolerated the exercise oncology program. <h3>Conclusions</h3> The RTC has been valuable in identifying functional deficits and informing appropriate triage criteria to further tailor rehabilitation and exercise program referral. This initial data will inform the ongoing triage of neuro-oncology patients in Calgary, Alberta. <h3>Author(s) Disclosures</h3> No conflict of interest to disclose.

Abstract P4-12-12: Assessing the impact of the COVID-19 pandemic on cancer treatment decision-making and care experiences

Abstract BACKGROUND: While the COVID-19 pandemic has reshaped how oncology is practiced, we sought to understand itseffects on treatment decision-making and care experiences amongst cancer patients at the Tom BakerCancer Centre in Calgary, Canada. METHODS: A 24 item, cross-sectional survey was developed based on literature review and iterative feedback fromoncology physicians, nurses, and a patient advisor. Survey domains included fear of COVID-19 andperceived risk, uptake of COVID-19 public health measures, cancer treatment decision-making duringthe pandemic, and cancer care experiences during the pandemic. Demographic, cancer and treatment-related information was obtained from the electronic medical record for patients who consented andcompleted the survey. In the first quarter of 2021, 161 patients accrued including 44 breast cancerpatients. The cohort characteristics and survey responses were summarized using descriptive statistics. RESULTS: For the 44 participants with breast cancer, all were female and the median age was 59 years (range 35-83 years). Our breast cancer cohort was almost evenly split between those with stage I-III (45.5%) andthose with metastatic disease (54.5%). Time since diagnosis was as follows: less than 1 year (17patients), 1-3 years (10 patients), 3-5 years (5 patients), and more than 5 years (9 patients). Treatmentsreceived since declaration of the pandemic included: surgery (21 patients), radiation (17 patients),chemotherapy (25 patients), endocrine therapy (25 patients), and other systemic therapies such as boneand anti-HER2 agents (15 patients). Just over half of the participants (54.5%) agreed or strongly agreedthat they were at increased risk of contracting COVID19; however, fewer patients expressed beinguncomfortable thinking about COVID-19 (45.4%), afraid of COVID-19 (38.6%), or fearful of dying fromCOVID19 (31.8%). The vast majority (&amp;gt;93%) of patients followed public health recommendations formitigating the risk of contracting COVID-19 (i.e. masking, frequent hand washing/sanitization, and socialdistancing) and 70.4% expressed a willingness to receive the vaccine when available. Of therespondents, 19 had undergone testing for COVID-19 at least once and 3 tested positive. Only 2 patientsreported that their surgical course was altered due to the pandemic and no patients declinedtreatments or perceived delays or modifications in therapies otherwise. Of 25 breast participants whohad experienced a cancer-related telehealth appointment during the pandemic, 21 (84%) agreed orstrongly agreed with being satisfied with the encounter. CONCLUSION: The COVID-19 pandemic caused minimal perceived disruption to care amongst a small cohort of breastcancer patients being treated at our centre. While experience with a cancer-related telehealthappointment was not universal, our findings support acceptability of its use. Citation Format: Noura Alsafar, Desiree Hao, Nimira Alimohamed, Sunil Samnani, Sasha Lupichuk. Assessing the impact of the COVID-19 pandemic on cancer treatment decision-making and care experiences [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-12-12.

Impact of COVID-19 on the Diagnosis and Management of Multiple Myeloma: Experience from a Canadian Center.

The impact of coronavirus disease-19 on the management of multiple myeloma (MM) has been recognized. However, the real effect on clinical outcomes remains poorly understood. We describe a local experience of the management of MM patients and report their outcomes during the current pandemic. All consecutive symptomatic MM patients seen at our center since 03/20 were evaluated. A cohort of 156 patients diagnosed from 01/19 to 12/20 was analyzed to interrogate differences in presentation patterns. A total of 553 MM patients were seen and/or treated at Tom Baker Cancer Center in the year of 2020. From those, 47.1% (n = 261) were tested for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Sixteen patients tested positive and data are presented. In addition, a decrease of 21.7% in the rate of new smoldering MM/MM diagnosis was observed in 2020 as compared to 2019. Further, an increase in deaths was also observed in 2020. Our study confirms an increase lethality for MM patients infected with SARS-CoV-2. A balance between safety and need for cancer control should be emphasized.

Complementary and Alternative Medicine Online Learning Intervention for Oncology Healthcare Providers: A Mixed-Methods Study.

Introduction:With the increased usage of complementary approaches in oncology comes the need for its integration into healthcare professional (HCP) education. The purpose of this single-arm, mixed-methods study was to examine the feasibility and benefits of a brief complementary and alternative medicine (CAM) learning intervention for improving HCP knowledge, attitudes, and practices regarding CAM use in cancer care, and explore the experiences of participating HCPs.Methods:HCPs from the Tom Baker Cancer Centre in Alberta, Canada, were invited to participate in 3 online interactive learning modules that reviewed: (1) basic CAM information, (2) HCP-patient CAM communication, and (3) evidence-based CAM decision support. The study survey consisted of attitude (n = 14), knowledge (n = 31), and practice (n = 31) items, administered at baseline and two-months post-intervention. Semi-structured interviews were conducted with a subset of participants.Results:Approximately 300 HCPs were invited to participate, of which 105 expressed interest in the study (35%), and 83 of them consented to participate (79%). The intervention completion rate was 73% (61/83 HCPs). There was a significant pre-post change in HCPs’ attitudes and, to a lesser extent, knowledge and practices related to CAM (8/14 attitude items changed pre-post compared to 13/31 knowledge items and 5/31 practice items), in which more HCPs reported patients should be assisted in making complementary therapy (CT) decisions, exhibited greater knowledge about CAM, and more often engaged in a CAM-related clinical practice. Qualitative findings supported the beneficial effects of the modules, with HCPs describing themselves as being more likely to ask patients about their CAM use and referring them to credible CAM resources. Nonetheless, the majority did not feel adequately prepared to make recommendations about specific CTs, even after the intervention.Conclusion:The current study suggests that online CAM learning offers a feasible and potentially promising intervention for improving oncology HCP knowledge, attitudes, and practices regarding CAM, warranting further investigation. This study highlights a need for institutional resources to help HCPs fully integrate CT decision support into cancer patient care. A coordinated evidence-based CAM program at cancer centers may help ensure that all patients’ CAM-related needs are properly attended to.

The prognostic impact of bone metastasis in patients with metastatic urothelial carcinoma treated with first-line platinum-based chemotherapy.

Background:In metastatic urothelial cancer (mUC), bone metastasis (BM) are associated with significant morbidity and mortality, yet their role as an independent prognostic variable remains unclear. We aimed to determine the impact of BM on overall survival (OS) in patients with mUC treated with first-line platinum-based chemotherapy (PBC).Methods:mUC patients receiving PBC at the Princess Margaret Cancer Center, Tom Baker Cancer Center, or Cross Cancer Institute from January 2005 to January 2018 were identified retrospectively using central pharmacy database records. Patient disease, treatment, and response characteristics were collected. Progression-free survival (PFS) and OS were estimated using the Kaplan–Meier method. Variables reaching significance (p < 0.05) in univariable analysis (UVA) of survival (OS) were included in multivariable analysis (MVA) (Cox).Results:Overall, 376 patients with a median follow-up of 16.8 (range: 2.2–218.3) months were included. Median age was 67 (range: 28–91) years, 76% were male, 63% had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0–1, and 41% had BM. All patients received first-line PBC. Patients with BM had inferior median PFS (4.9 months (95% CI 3.6–6.2) versus 6.5 months (95% CI 5.4–7.6), p = 0.03) and median OS (8.8 months (95% CI 7.8–9.7) versus 10.8 months (95% CI 9.1–12.5), p = 0.002). In UVA, ECOG PS 2–3 (p < 0.001), presence of BM (p = 0.002), and WBC count ⩾ 11,000 cells/mm3 (p = 0.001) were associated with inferior survival. Prior cystectomy (p < 0.001) and lack of progression (stable disease, partial or complete response) on treatment was associated with improved OS (p < 0.001). These variables maintained significance in MVA.Conclusion:In this retrospective study, mUC patients with BM had worse OS suggesting that BM may be an independent negative prognostic factor and including BM as a stratification factor in future mUC clinical trial designs may be warranted. A greater focus must be placed on novel therapeutic strategies to better manage BM to reduce both morbidity and mortality.

P.004 Autoimmune Encephalitis: Modifiable and Non-Modifiable Predictors of Relapse

Background: Approximately 25% of encephalitis cases in North America are immune mediated. For most forms of autoimmune encephalitis (AIE), risk of relapse is unclear and little evidence exists to guide which patients have the highest risk and whether standard treatments reduce this risk. Our objective was to determine the factors associated with AIE relapse. Methods: We performed a chart review consisting of patients with AIE presenting to the Calgary Neuro-Immunology Clinic and Tom Baker Cancer Centre between 2015 and 2020. Predictors of relapse were determined with use of t-test. Results: Outcome data was assessable in 39/40 patients, 17/39 (44%) patients relapsed. Seropositive patients and those with abnormal CSF were more likely to relapse, although neither reached statistical significance (p=0.12, 0.059). Patients with longer duration of steroid and steroid sparing treatment prior to relapse, and those on steroids at the time of relapse, had milder relapses (p=0.024, 0.026, 0.047). There was no difference in steroid or steroid sparing treatment use at 3, 6, and 12 months between groups. Conclusions: Risk of relapse in AIE is high (44%), with most relapses occurring in the first 3 years. Continuous immunosuppression lessens the severity of relapse, although our study did not confirm it reduced the occurrence of relapse.

Post-Autologous Stem Cell Transplantation Therapy for Multiple Myeloma Patients: Impact on Clinical Outcomes

Introduction Autologous stem cell transplantation (auto-SCT) has dramatically improved the outcomes for patients with MM. While the outcomes are better, still most patients will inevitably relapse. Two different approaches have been reported aiming to improve clinical outcomes: consolidation and maintenance. In the present study, we evaluate the impact of post-autoSCT therapy over survival outcomes. Methods All consecutive patients who underwent single auto-SCT at Tom Baker Cancer Center from 01/04 to 03/17 were evaluated. A p value of <0.05 was considered significant. Survival curves were constructed according to the Kaplan-Meier method and compared using the log rank test. Results 302 consecutive patients with MM who underwent single auto-SCT at our Institution over the defined period were evaluated. Clinical characteristics are shown in Table 1. 78 patients did not receive any form of post-autoSCT therapy, 93 patients had received consolidation followed by maintenance and 130 received some form of maintenance only. At the time of analysis, 201 patients are still alive and 161 have already progressed. A trend towards better median overall survival (OS) was observed for those patients receiving post-autoSCT therapy (95.9 vs 69.7 months, p=0.2) (Fig 1a). Furthermore, patients receiving consolidation followed by maintenance and maintenance only had a median PFS of 45 and 36.9 months, compared to 24.1 months for those with no post-autoSCT therapy (p=0.0001) (Fig 1b). In addition, high-risk cytogenetic (HRC) patients defined by FISH (t(4;14), t(14;16) and p53 del) had a better OS in the post-autoSCT therapy group (56 vs 26 months, p=0.04). Median PFS was also longer in the post-autoSCT therapy group for the HRC group (22.5 vs 9.1 months, p=0.001). In conclusion, post-autoSCT therapy is an important approach that has improved clinical outcomes for MM patients undergoing single autoSCT. Patients with HRC MM seemed to have better outcomes as a result of this strategy. However, survival still remains poor compared to standard risk myeloma patients. The effect of consolidation is currently controversial and requires further assessment with long-term follow-up and subset analysis to better estimate patients that might benefit from it. [Display omitted] DisclosuresJimenez-Zepeda:Celgene: Honoraria; Janssen: Honoraria; Takeda: Honoraria; Amgen: Honoraria. Neri:Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding. Bahlis:Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Minimal Residual Disease (MRD) Assessed By Flow Cytometry in Patients with AL Amyloidosis Treated with Cyclophosphamide, Bortezomib and Dexamethasone (CyBorD)

Introduction In the field of multiple myeloma (MM), the clinical utility of minimal residual disease (MRD) has been an area of extensive research. The use of MRD assessment in AL amyloid patients is an emerging area of interest. In the present study, we aimed to describe the rate of MRD negativity for patients treated with CyBorD at our Institution. Methods All consecutive AL amyloid patients treated with CyBorD at Tom Baker Cancer Center from 01/13 to 04/17 were evaluated. MRD was assessed by multiparameter flow cytometry as per Euroflow consensus guidelines in patients with confirmed complete response. A p value of <0.05 was considered significant. Survival curves were constructed according to the Kaplan-Meier method and compared using the log rank test. Results 41 consecutive patients with newly diagnosed (n=35) and relapsed AL (n=6) who had received CyBorD at our Institution over the defined period were evaluated. 5 patients were excluded due to lack of follow-up or enrolment in clinical trials. Clinical characteristics are shown in Table 1 for the remaining cases (n=36). CyBorD was administered with bortezomib at 1.3-1.5 mg/m2 SC or IV for 3-4 weeks on a weekly basis in 34 cases and biweekly in 2 patients, cyclophosphamide was given at 300 mg/m2 on days 1, 8, 15 and 22 and dexamethasone at 20-40 mg/PO on days 1, 8, 15 and 22. After a median of 5 cycles, ORR was seen in 91.6% of cases with a PR of 36.1%, VGPR of 27.8% and CR of 27.8%. MRD negativity was observed in 5/10 cases with complete response. MRD negativity rate of 13.8% was reported for the whole group of patients. Organ and cardiac responses were observed in 36.1% and 27.3%, respectively. Median OS was similar between MRD positive and negative cases (NR vs NR, p=0.1) (Fig 1a). However, none of the MRD negative cases has died or progressed. A trend towards better PFS was observed in the MRD negative cases (p=0.06) (Fig1b). In conclusion, MRD negativity was observed in ~15% cases of AL patients treated with CyBorD after a median of 5 cycles. Further studies to assess the impact of MRD negativity on clinical outcomes and its role for guided therapy are required. [Display omitted] DisclosuresJimenez-Zepeda:Takeda: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Amgen: Honoraria. Neri:Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding. Bahlis:Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Early Relapse in Transplant-Eligible MM Patients Undergoing Auto-SCT Followed By Maintenance Therapy

Introduction Autologous Stem Cell transplantation (auto-SCT), still remains as the standard therapy offered to patients with MM deemed to be eligible for this strategy. Unfortunately, even with the advent of novel and efficacious approaches such as new upfront induction regimens, consolidation and maintenance, patients will progress. Based on the above mentioned, we aimed to assess the impact of maintenance on Early Relapse and its association with predictor factors of survival. Methods All consecutive patients who underwent single auto-SCT at Tom Baker Cancer Center from 01/06 to 03/16 were evaluated. ER was defined as per recent publications (<12 months from auto-SCT). A p value of <0.05 was considered significant. Survival curves were constructed according to the Kaplan-Meier method and compared using the log rank test. Results 215 consecutive patients with MM who underwent single auto-SCT followed by maintenance therapy at our Institution over the defined period were evaluated. Clinical characteristics are shown in Table 1. At the time of analysis, 154 patients are still alive and 99 have already progressed. Among these cases, 21 patients have relapsed in <12 months (ER) from auto-SCT (20%) and 57 have relapsed within 24 months post auto-SCT. 14 out of 21 patients with ER (<12 months) and 26/57 (relapse <24 months) had HRC (high-risk cytogenetics) (66% and 45.6%, respectively, p=0.0001 compared to non-ER). Patients with <VGPR at day-100 post-ASCT exhibited a shorter PFS (25 months vs 46.8 months, p=0.006). Patients with <VGPR at day-100 post-ASCT were more likely to develop ER<12 months (31% vs 15%). (p=0.05) Median OS was shorter for the ER (<12 months) group (14 months) compared to those relapsing within12-24 months and >24 months (58 months and non-reached, respectively, p=0.0001, Fig 1) In conclusion, patients with ER after auto-SCT remain to be a challenge. Even with the advent of novel agents in the setting of maintenance, patients with ER had poor outcomes. ER for patients treated with maintenance therapy should be characterized better. ER defined as <24 months should be investigated in the setting of maintenance therapy. More biological insights on ER cases are needed to further improve survival outcomes. [Display omitted] DisclosuresJimenez-Zepeda:Amgen: Honoraria; Takeda: Honoraria; Janssen: Honoraria; Celgene: Honoraria. Neri:Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Bahlis:Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Bortezomib-Maintenance for Patients with AL Amyloidosis: A Single Center Experience

Introduction AL amyloidosis is a clonal plasma cell disorder characterized by the deposition of monoclonal light-chain fibrils into extracellular tissues, leading to organ dysfunction. Data on maintenance in AL amyloidosis is scarce and only a small study with high-dose dexamethasone followed by maintenance dexamethasone/interferon is available in the medical literature. Based on the above mentioned, we aimed to explore the role of bortezomib maintenance for the treatment of AL amyloidosis. Methods All consecutive AL amyloid patients treated at Tom Baker Cancer Center with bortezomib-containing regimens (BCR) from 01/09 to 03/17 were evaluated. A p value of <0.05 was considered significant. Survival curves were constructed according to the Kaplan-Meier method and compared using the log rank test. All statistical analyses were performed by using the SPSS 24.0 software. Results 63 consecutive patients with AL who had received BCR at our Institution over the defined period were evaluated. Clinical characteristics are shown in Table 1. 19 patients had received maintenance bortezomib (bortezomib 1.3-1.5 mg/m2 every other week) and 10 out of these 19 received more than 12 months of therapy. Median bortezomib dose on the maintenance group was 42.9 mg/m2 compared to 15.6 mg/m2 in the no-maintenance group (p=0.03). At the time of analysis, 43 patients are still alive and 14 have already progressed. No differences with regards to best response rates were seen between the maintenance and no-maintenance groups (VGPR/CR rate of 68.4% vs 63.6%, p=0.2). Further, overall survival was similar between patients receiving or not bortezomib maintenance (NR vs 72 months, p=0.6) However, a trend towards better PFS was observed for the group receiving maintenance (65 vs 37 months, p=0.3) (Fig 1) In conclusion, BCR are efficacious for the treatment of AL amyloidosis. The present study reports on the use of bortezomib maintenance for the treatment of AL patients. Our study failed to identify a significant benefit on response rates or survival but further investigation is needed to assess whether a subgroup of patients might benefit from this strategy, especially now that novel tools of monitoring such as Minimal Residual Disease assessment are investigated. [Display omitted] DisclosuresJimenez-Zepeda:Celgene: Honoraria; Takeda: Honoraria; Amgen: Honoraria; Janssen: Honoraria. Neri:Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Bahlis:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

P50.10 Intravenous (IV) versus IV/oral route of etoposide administration: impact on real-world SCLC survival outcomes

Platinum-etoposide doublet (PE) is the recommended first-line (1L) chemotherapy for small cell lung cancer (SCLC). Evidence shows that oncology patients prefer oral treatment to IV. This study compared outcomes between 1L intravenous (IV), and IV followed by oral (IV/oral) route of etoposide administration in real-world SCLC patients in Alberta, Canada. SCLC patients who were diagnosed between 2010 and 2016 and completed 1L etoposide at an academic tertiary cancer centre, (Tom Baker Cancer Centre) were included. Data were retrieved from the Glans-Look database excluding those with mixed histology. Outcomes explored included, a] overall survival, (OS), the time in months from diagnosis date to death/last contact, b] tumor objective response rate (ORR), the complete and partial responses as defined by the RECIST v1.1 criteria, using diagnostic imaging reports within 4-8 weeks post 1L or as reported in oncologist progress notes, and c] 1L-related toxicity rate, derived from progress notes, graded using the CTCAE criteria (version 5). Also measured was the progression free survival (PFS): time difference in months from diagnosis date to first progression post 1L or death, whichever occurs first. Comparison between IV/oral and IV groups was performed using Fisher’s Exact (point estimates), Log-Rank tests (Kaplan-Meier survival estimates) and Cox proportional hazard model (survival outcome predictors). A priori statistical significance was p < 0.05. Analyses were performed using SPSS statistical software (version 25). There were 222 patients, 1L was mostly PE [93%] employing etoposide in combination with cisplatin [61%] or carboplatin [32%]. 168 [76%] were IV/oral group. Median age was 66 years, 132 [60%] female, and 138 [62%] had extensive stage SCLC (ES). Performance status (ECOG) was 0-2 in 112 (51%), ≥3 in 9 (4%) and unknown in 101 (46%) patients. IV and IV/oral patients have similar characteristics, but compared to IV/oral, the IV group had less limited stage disease (LS), [p=0.28]. 100 patients experienced grade 3 or 4 toxicities, mainly neutropenia [83%]. The rates were similar for IV/oral versus IV group, p= 0.36. Stratified by stage however, toxicity from IV was greater in LS than ES patients [60 vs 39%]. Overall, ORR for IV/oral versus IV group was 71% vs 66%, [p=0.85]. Within stage, ORR was 79 vs. 89% in LS [p< 0.01] and 58 vs 71% in ES [p=0.23], IV/oral relative to IV group. There was no statistically significant difference in PFS or OS with IV/oral relative to IV groups [PFS: 14 vs 12 months for LS; both 6 months for ES; OS: 32 vs 25 mo. for LS; 12 vs 14 mo. for ES]. Predictors of favorable survival include presence of grade 3 or 4 toxicity in LS [HR= 0.45, p=0.03] and second-line chemotherapy receipt in ES [HR= 0.46, p<0.01]. Consistent with previous reports, we found high oral treatment rate in real-world SCLC patients and no statistically significant differences in SCLC survival outcomes comparing IV/oral versus IV group. Future studies may explore why severe chemotherapy-related toxicity (grade 3 or 4) in LS patients predicts favorable survival.

The prognostic impact of bone metastasis in urothelial carcinoma treated with first-line platinum-based chemotherapy.

415 Background: Metastatic urothelial carcinoma (mUC) is an aggressive disease with a median overall survival (OS) of ≈ 15 months. In the first-line setting, key prognostic factors include ECOG performance status, white blood cell count, and response to treatment per the Galsky nomogram. Bone metastases (BM) in mUC are associated with morbidity and mortality but are grouped with visceral disease; hence, their impact on prognosis is not well established. We aimed to assess the survival impact of BM in mUC patients treated with first-line platinum-based chemotherapy (PBC). Methods: A retrospective collection of patient and tumor characteristics, with clinical response to treatment (complete response [CR], partial response [PR]; stable disease [SD] or progressive disease [PD]) for patients treated at Princess Margaret Cancer Centre, Tom Baker Cancer Centre, and Cross Cancer Institute from 2005-2018 was performed. Progression-free survival (PFS) and OS were estimated using the Kaplan-Meier method. Univariate (UVA) followed by multivariate analysis (MVA) of patient variables [Cox] using PFS and OS was performed. Results: Overall 376 mUC patients were included; 222 (59%) had soft-tissue metastases (STM) only, 70 (19%) had bone-only metastases, and 84 (22%) had both STM and BM. Overall, 35% had PR or CR, 19% had SD, and 39% had PD (7%: unknown response). The median PFS and OS for the whole cohort were 5.6 months (95%CI: 4.8-6.4) and 9.7 months (95% CI: 8.8-10.8) respectively. Select UVA by metastatic site showed inferior PFS for bone-only (p=0.03) and combination STM and BM (p=0.017). Only combination STM and BM were significant on UVA for OS (p=0.002). MVA showed that bone-only metastases (p=0.03) and ECOG 3-4 (p&lt;0.0001) were associated with worse PFS (Table). Predictors of worse OS were the combination of STM and BM (p=0.02), ECOG 3-4 (p=0.001), and WBCs ≥ULN (p=0.02), (Table). Conclusions: BM are a significant predictor of worse outcomes for mUC patients treated with first-line PBC. Consideration as a treatment stratification factor for future studies is suggested. Strategies for the treatment of mUC patients with BM (ie: bone targeted agents) in the first-line setting should be addressed in future trials. [Table: see text]

Durability of Complete Response to Intralesional Interleukin-2 for In-Transit Melanoma.

BackgroundIntralesional injection of interleukin-2 (IL-2) for in-transit melanoma (ITM) is associated with a high rate of complete response. However, there is a paucity of data on treatment durability and long-term outcomes.ObjectivesTo provide long-term data on patients with a complete response to IL-2 therapy for ITM.MethodsConsecutive patients with ITM, treated with intralesional IL-2 therapy, at the Tom Baker Cancer Center were identified from April 2009 to August 2019. All patients received at least 4 cycles (every 2 weeks) of IL-2 (5 MIU/mL). Complete response was defined as sustained (ie, 3 months) clinical complete remission of all known in-transit disease.ResultsSixty-five patients were treated with curative intent for in-transit disease with intralesional IL-2. Complete clinical response was identified in 44.6% (29/65). In this subset of patients, the median number of lesions per patient was 9 (range 1-40). The median total dose of IL-2 was 0.8 mL (IQR 0.4-1.5) per lesion. One patient received isolated limb infusion and 13.8% (4/29) received systemic immunotherapy as part of their initial management. At a median follow-up of 27 months (IQR 16-59), 34.5% (10/29) developed recurrent disease. Of these patients, 50.0% (5/10) presented with synchronous in-transit and distant metastases. The median time to recurrence was 10.5 months (IQR 5.8-16.3).ConclusionWith long-term follow-up, 65.5% of complete responders have a durable response to intralesional IL-2 therapy. In this cohort of patients, local in-transit recurrence is most likely to occur within 12 months and is often associated with concomitant distant disease.

Retrospective Review of Treatment Patterns and Outcomes of DLBCL in the Very Elderly: A Single Centre Experience

Treatment of diffuse large B-cell lymphoma (DLBCL) in patients over the age of 80 years is challenging due to existing comorbidities and frailty in the face of an aggressive disease. Standard chemo-immunotherapy can sometimes be difficult to administer to these patients due to toxicities, requiring dose adjustments and interruptions. There are no definitive guidelines to help direct therapy in these patients and treatment decisions are often subjective. The objective of this study was to retrospectively review treatment patterns and outcomes of DLBCL in patients over the age of 80 years. All patients who were referred to the Tom Baker Cancer Centre in Calgary, Alberta from 2012-2017 were retrospectively reviewed. Data collected included patient characteristics, comorbidities that were used to calculate the Charlson Comorbidity Index (CCI), revised International Prognostic Index (IPI), chemotherapy regimen(s), dose reductions and interruptions, and mortality. The primary outcome was overall survival (OS). A total of 123 patients with DLBCL over the age of 80 were referred to the cancer center at diagnosis. The average age was 84.9 years (IQR 82-87.5). At diagnosis, 62.3% of patients had an ECOG≥2 and 65.8% of patients had an IPI greater than 3. The most common comorbidities described were a history of congestive heart failure (20%), diabetes (16%) and MI (20%). Patients received either curative intent chemotherapy (62.6%) or palliative therapy (37.4%). The curative intent chemotherapy regimens included dose-reduced R-CHOP (31.5%), full dose R-CHOP (11.8%), R-CEOP (14.2%), and other chemotherapy regimens (3.9%). Palliative therapy included PEP-C chemotherapy (4.7%) or treatment with steroids (13.4%) or no treatment at all (20.5%). There were 28 patients (22.7%) who received adjunctive radiotherapy for limited stage or bulky disease. Risk factors at diagnosis for mortality included elevated LDH (OR 3.14, CI 1.42-6.93, p&amp;lt;0.05) and ECOG≥2 (OR 2.15, 0.99-4.67, p&amp;lt;0.05). Every 1 point increase in patients' CCI at diagnosis was associated with an increased risk of death (OR 1.38, 95% CI 1.05-1.82, p=0.02). The cumulative OS at 2 years was 44.7%. Patients who received any amount of curative intent chemotherapy did better than the palliative group (See Figure 1). Within the chemotherapy group, 33.3% of patients stopped their treatment early. These patients had better survival than the palliation group (HR 0.56, 95% CI 0.34-0.94, p=0.04) but overall still had a poor prognosis with a median OS of 10.9 months. Very elderly patients with DLBCL still remain a very challenging population to treat with most patients presenting with high risk disease and poor functional status. Without chemotherapy, the overall prognosis is dismal. Patients who are able to complete treatment with chemo-immunotherapy have the best survival despite the risk of toxicities associated with more intensive treatment but that survival is significantly shortened if they are unable to complete their planned cycles. Disclosures Owen: AbbVie, F. Hoffmann-La Roche, Janssen, Astrazeneca, Merck, Servier, Novartis, Teva: Honoraria.