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Purpose: Proliferation of T-follicular helper (TFH) CD4+ T cells is a postulated pathogenic mechanism for T-cell non-Hodgkin lymphomas (T-NHL). The inducible T-cell costimulator (ICOS) is highly expressed by TFH, representing a potential target. MEDI-570 is a monoclonal antibody against ICOS, which eliminates ICOS+ cells in preclinical models. Patients and Methods: We report the safety, pharmacokinetics (PK), pharmacodynamics (PD), and clinical activity of MEDI-570 in T-NHL. NCI-9930 is a phase I, first-in-human study of MEDI-570 in relapsed/refractory malignant T-NHL known to express ICOS. MEDI-570 was administered intravenously every 3 weeks for up to 12 cycles. Primary endpoints were safety, dose-limiting toxicities (DLT), and recommended phase II dose (RP2D). Secondary and exploratory endpoints included efficacy parameters and various correlative studies. This study is supported by the National Cancer Institute (NCT02520791). Results: Twenty-three patients were enrolled and received MEDI-570 at five dose levels (0.01–3 mg/kg). Sixteen (70%) had angioimmunoblastic T-cell lymphoma (AITL); median age was 67 years (29–86) and the median prior lines of therapies was 3 (1–16). Most common grade 3 or 4 adverse events were decreased CD4+ T cells (57%), lymphopenia (22%), anemia (13%), and infusion-related reactions (9%). No DLTs were observed. The RP2D was determined at 3 mg/kg. Analysis of T-cell subsets showed reductions in CD4+ICOS+ T cells reflecting its effects on TFH cells. The response rate in AITL was 44%. Conclusions: MEDI-570 was well tolerated and showed promising clinical activity in refractory AITL. MEDI-570 resulted in sustained reduction of ICOS+ T lymphocytes.

Interim imaging with computed tomography (iCT) to assess response is common during frontline chemoimmunotherapy for follicular lymphoma (FL), but there is little evidence of its utility. We retrospectively reviewed outcomes of iCT in 190 patients with biopsy-proven FL who received first-line chemoimmunotherapy from 2003-2018. Most iCTs showed partial response (PR, 83%), with a minority showing complete response (CR, 8%) or stable disease (5%). Seven patients (4%) had radiographic disease progression (PD) on iCT; on repeat biopsy, four had another malignancy identified and three had transformation to DLBCL. Only one had asymptomatic PD. The 3-year PFS of all patients was 74% (median follow up 75 months). Patients with PR on iCT had similar 3-year PFS and OS as those with CR. In conclusion, iCT has limited utility in identifying patients with asymptomatic early progression during first-line treatment. Patients with PD mid-treatment warrant biopsy to identify histologic transformation or other malignancies.

Supplemental Figure 2. MEDI-570 effects on lymphocyte and leukocyte populations. Baseline-normalized, absolute counts (ABS) of circulating cell populations were plotted on study days 1, 7, 14 and 21 from patients enrolled in each dose group as indicated. A) Total CD3+CD8+ cytotoxic T cells B) CD14+ monocytes C) CD3-CD56+ and/or CD16+ NK cells D) CD3-CD19+ B cells.

Supplemental Figure 1. CD4 count recovery after end of treatment (by local site collection)

Purpose:Proliferation of T-follicular helper (TFH) CD4+ T cells is a postulated pathogenic mechanism for T-cell non-Hodgkin lymphomas (T-NHL). The inducible T-cell costimulator (ICOS) is highly expressed by TFH, representing a potential target. MEDI-570 is a monoclonal antibody against ICOS, which eliminates ICOS+ cells in preclinical models.Patients and Methods:We report the safety, pharmacokinetics (PK), pharmacodynamics (PD), and clinical activity of MEDI-570 in T-NHL. NCI-9930 is a phase I, first-in-human study of MEDI-570 in relapsed/refractory malignant T-NHL known to express ICOS. MEDI-570 was administered intravenously every 3 weeks for up to 12 cycles. Primary endpoints were safety, dose-limiting toxicities (DLT), and recommended phase II dose (RP2D). Secondary and exploratory endpoints included efficacy parameters and various correlative studies. This study is supported by the National Cancer Institute (NCT02520791).Results:Twenty-three patients were enrolled and received MEDI-570 at five dose levels (0.01–3 mg/kg). Sixteen (70%) had angioimmunoblastic T-cell lymphoma (AITL); median age was 67 years (29–86) and the median prior lines of therapies was 3 (1–16). Most common grade 3 or 4 adverse events were decreased CD4+ T cells (57%), lymphopenia (22%), anemia (13%), and infusion-related reactions (9%). No DLTs were observed. The RP2D was determined at 3 mg/kg. Analysis of T-cell subsets showed reductions in CD4+ICOS+ T cells reflecting its effects on TFH cells. The response rate in AITL was 44%.Conclusions:MEDI-570 was well tolerated and showed promising clinical activity in refractory AITL. MEDI-570 resulted in sustained reduction of ICOS+ T lymphocytes.

Supplemental Tables and Protocol Description

Supplemental Figure 3. Representative baseline pre-treatment tumor specimen of a patient with AITL (H&E, ICOS staining and CD3 staining by IHC)

Rationale: The objective was to assess the cost-effectiveness of staging positron emission tomography/computed tomography (PET/CT) in early-stage follicular lymphoma from the Canadian health care system perspective. Methods: The study population was FL patients staged as early-stage using conventional CT imaging and planned for curative-intent radiation therapy (RT). A decision analytic model simulated the management after adding a staging PET/CT vs. using staging CT alone. In the no-PET/CT strategy, all patients proceeded to curative-intent RT as planned. In the PET/CT strategy, PET/CT information could result in an increased RT volume, switching to a non-curative approach, or no change in RT treatment as planned. Subsequent disease course was described using a state-transition cohort model over a 30-year time horizon. Diagnostic characteristics, probabilities, utilities and costs were derived from the literature. Baseline analysis was performed using quality-adjusted life years (QALYs), costs (2019 Canadian dollars, CAD$) and the incremental cost-effectiveness ratio. Deterministic sensitivity analyses were conducted, evaluating net monetary benefit at a willingness-to-pay threshold of $100,000/QALY. Probabilistic sensitivity analysis using 10,000 simulations was performed. Costs and QALYs were discounted at a rate of 1.5%. Results: In the reference case scenario, staging PET/CT was the dominant strategy, resulting in an average lifetime cost saving of $3,165 and a gain of 0.32 QALYs. In deterministic sensitivity analyses, the PET/CT strategy remained the preferred strategy for all scenarios supported by available data. In probabilistic sensitivity analysis, the PET/CT strategy was strongly dominant in 77% of simulations (i.e., reduced cost and increased QALYs), and was cost-effective in 89% of simulations (i.e., either cost-saving or with an incremental cost-effectiveness ratio below $100,000/QALY). Conclusion: Our analysis shows that the use of PET/CT to stage early-stage FL patients reduces cost and improves QALYs. Patients with early-stage FL should undergo PET/CT prior to curative-intent RT.

Pretransplant Deauville score (DS) is an imaging biomarker used for risk stratification in relapsed/refractory classical Hodgkin lymphoma (cHL). However, the prognostic value of residual metabolic tumor volume (rMTV) in patients with DS 4-5 has been less well characterized. We retrospectively assessed 106 patients with relapsed/refractory cHL who underwent autologous stem cell transplantation. Pretransplant DS was determined as 1-3 (59%) and 4-5 (41%), with a markedly inferior event-free survival (EFS) in patients with DS 4-5 (hazard ratio [HR], 3.14; p = .002). High rMTV

Background: The use of virtual care, defined as providing healthcare in ways other than in-person visits, dramatically increased during the COVID-19 pandemic to minimize infection risk and maintain care provision. However, the majority of studies evaluating the use of virtual care in oncology have focused on patients with solid tumor malignancies. Patients with hematologic malignancies represent a unique population related to their underlying malignancy and treatment, but the extent to which virtual care has been successfully integrated into clinical practice is unknown. As the demand for incorporating virtual care into routine clinical practice grows, understanding how to safely and effectively use virtual care in this specific patient population is essential. Methods: A scoping review was conducted to describe the use of virtual care in the management of patients with hematologic malignancies and to examine physician- and patient-reported outcomes based on its use. A comprehensive search strategy was used to identify articles on the use of virtual modalities (digital applications, phone visits, or video visits) to deliver routine clinical care to patients with hematologic malignancies published in English between January 2000 and April 2021 in the following databases: PubMed, Medline, EMBASE, CINAHL and Scopus. No restrictions were applied to the phase of care (surveillance, active treatment, and or survivorship). A combination of search terms to encompass hematologic malignancies and virtual care was used. Screening and data abstraction were performed by two independent reviewers (AS, AV) and conflicts were adjudicated by two additional reviewers (DR, AP). Data were extracted to assess the study design, population, setting, patient characteristics, virtual care methodology and study results. Results: A total of 350 abstracts were screened and 60 studies underwent full-text review. Of these, 15 studies met inclusion criteria (13 retrospective studies, 1 prospective pilot study, and 1 randomized controlled trial). The majority of papers were published from 2020 onward (Figure 1). Three studies found that app-based tools were effective in monitoring patient symptoms and triggering alerts which resulting in sooner follow-up if indicated. One app-based tool was also used in a resource limited country during the COVID-19 pandemic to allow for communication between hematologists and their patients. Four studies described the use of phone-based interventions for new consults and follow-up visits. Phone visits for used even in high-risk patients (for example, in 29 out of 50 patients with chronic graft-versus-host disease after allogeneic stem cell transplant). Five studies found that videoconferencing, with both physicians and oncology nurses, was highly rated by patients. Emerging themes included high levels of patient satisfaction across all domains of virtual care. Provider satisfaction scores were rated lower than patient scores, with concerns about technical issues leading to challenges with virtual care. Four studies found that virtual care allowed providers to promptly respond to patient concerns, specifically when patients were experiencing side-effects or had questions about their treatment. One study also suggested a decreased risk of death when telemedicine was used to monitor symptoms in patients with diffuse large B-cell lymphoma. There were no data addressing the impact of virtual care on costs or resource utilization. Conclusion: The use of virtual care in patients with hematologic malignancies appears to be feasible, even in high-risk populations. Patients were highly satisfied with virtual care, although providers had some challenges related to the specific technologies. More research is needed to evaluate the optimal method of integrating virtual care, informed by a wider range of patient-related outcomes, as well as the downstream consequences of this integration for patient, providers, and health systems. Figure 1 Figure 1. Disclosures Prica: Astra-Zeneca: Honoraria; Kite Gilead: Honoraria.

The optimal hemoglobin (HgB) threshold for red blood cell transfusions in adult patients with myelodysplastic syndromes (MDS) has not been defined. We conducted a randomized multi-center study of two transfusion algorithms (liberal, to maintain Hgb 110-120 g/L, versus restrictive, 85-105 g/L) and combined our findings from RBC-ENHANCE with those of REDDS a previously published study of similar design. Primary objectives were measures of compliance to transfusion thresholds and the achievement of a 15 g/L difference in pre-transfusion Hgb. Secondary outcomes included measures of QOL, iron studies and safety. 66 patients were randomized between February 2015-2020, 33 to each arm in 15 international participating sites. The compliance was 58% and 81% in the restrictive and liberal arms respectively and the mean pre-transfusion Hgb thresholds for restrictive and liberal arms were 85.9 (SD 9) and 98.8 g/L (SD 9). Patients in the liberal arms experienced a mean of 3.4 (SD 2.6) more transfusion visits and received a mean of 5.3 (SD 5.5) extra units of blood during the 12-week study. Selected QOL scores were superior pre-transfusion and more patients achieved clinically important differences in the liberal arm. Further data are needed to establish the feasibility of liberal transfusion policies in MDS outpatients. Trial Registration: REDDS: ISRCTN26088319 RBC-ENHANCE: NCT 02099669

Autologous stem cell transplantation (ASCT) remains a key therapeutic strategy for treating patients with relapsed or refractory non-Hodgkin and Hodgkin lymphoma. Clonal hematopoiesis (CH) has been proposed as a major contributor not only to the development of therapy-related myeloid neoplasms but also to inferior overall survival (OS) in patients who had undergone ASCT. Herein, we aimed to investigate the prognostic implications of CH after ASCT in a cohort of 420 lymphoma patients using ultra-deep, highly sensitive error-correction sequencing. CH was identified in the stem cell product samples of 181 patients (43.1%) and was most common in those with T-cell lymphoma (72.2%). The presence of CH was associated with a longer time to neutrophil and platelet recovery. Moreover, patients with evidence of CH had inferior 5-year OS from the time of first relapse (39.4% vs. 45.8%, p = .043) and from the time of ASCT (51.8% vs. 59.3%, p = .018). The adverse prognostic impact of CH was not due to therapy-related myeloid neoplasms, the incidence of which was low in our cohort (10-year cumulative incidence of 3.3% vs. 3.0% in those with and without CH, p = .445). In terms of specific-gene mutations, adverse OS was mostly associated with PPM1D mutations (hazard ratio (HR) 1.74, 95% confidence interval (CI) 1.13-2.67, p = .011). In summary, we found that CH is associated with an increased risk of non-lymphoma-related death after ASCT, which suggests that lymphoma survivors with CH may need intensified surveillance strategies to prevent and treat late complications.

Rationale: Patients with hematologic malignancies requiring mechanical ventilation have historically experienced poor outcomes.Objectives: We aimed to determine whether body composition characteris...

Background Cost-effectiveness analyses embedded within randomized trials allow for evaluation of value alongside conventional efficacy outcomes; however, collection of resource utilization data can require considerable trial resources. Methods We re-analyzed the results from four phase III Canadian Cancer Trials Group trials that embedded cost-effectiveness analyses to determine the impact of minimizing potential cost categories on the incremental cost-effectiveness ratios. For each trial, we disaggregated total costs into component incremental cost categories and recalculated incremental cost-effectiveness ratios using (1) only the top 3 cost categories, (2) the top 5 cost categories, and (3) all cost components. Using individual trial-level data, confidence intervals for each incremental cost-effectiveness ratio simulation were generated by bootstrapping and descriptively presented with the original confidence intervals (and incremental cost-effectiveness ratios) from the publications. Results Drug acquisition costs represented the highest incremental cost category in three trials, while hospitalization costs represented the other consistent cost driver and the top incremental cost category in the fourth trial. Recalculated incremental cost-effectiveness ratios based on fewer cost components (top 3 and top 5) did not differ meaningfully from the original published results. Based on conventional willingness-to-pay thresholds (US$50,000–US$100,000 per quality-adjusted life-year), none of the re-analyses would have changed the original perception of whether the experimental therapies were considered cost-effective. Conclusions These results suggest that the collection of resource utilization data within cancer trials could be narrowed. Omission of certain cost categories that have minimal impact on incremental cost-effectiveness ratio, such as routine laboratory investigations, could reduce the costs and undue burden associated with the collection of data required for cancer trial cost-effectiveness analyses.

We conducted an analysis of indirect costs alongside the LY.12 randomized trial in patients with relapsed or refractory (R/R) aggressive non-Hodgkin lymphoma (NHL). Lost productivity data for Canadian patients and caregivers in the trial were collected at baseline and with each chemotherapy cycle pre-transplant, using an adapted Lost Productivity questionnaire. Mean per patient indirect costs were CAD 2999 for patients in the GDP arm and CAD 3400 in the DHAP arm. A substantial majority was not working or had to reduce their workload during this treatment time. Salvage chemotherapy for R/R aggressive NHL is associated with significant indirect costs to patients and their caregivers.

There are limited data regarding the combined value of the pretransplant Deauville score (DS) from a positron emission tomography scan and clinical risk factors in patients with relapsed/refractory aggressive non-Hodgkin lymphoma (NHL). We performed a retrospective analysis to assess the prognostic role of pretransplant DS in patients with relapsed/refractory aggressive NHL who underwent salvage chemotherapy and autologous stem cell transplantation (ASCT). We identified 174 eligible patients between January 2013 and March 2019. In multivariable analysis, pretransplant DS, B symptoms, and secondary International Prognostic Index (sIPI) were independent risk factors for event-free survival (EFS). These variables were used to derive an integrated risk score that categorized 166 patients with available information for all risk factors into 3 groups: low (n = 92; 55.4%), intermediate (n = 48; 28.9%), and high (n = 26; 15.7%). The new prognostic index showed a strong association with EFS (low-risk vs intermediate-risk hazard ratio [HR], 3.94; 95% confidence interval [CI], 2.16-7.17; P < .001; low-risk vs high-risk HR, 10.83; 95% CI, 5.81-20.19; P < .001) and outperformed models based on clinical risk factors or DS alone. These results were validated in 60 patients from an independent external cohort (low-risk vs intermediate-risk HR, 4.04; 95% CI, 1.51-10.82; P = .005; low-risk vs high-risk HR, 10.49; 95% CI, 4.11-26.73; P < .001). We propose and validate a new prognostic index that risk-stratifies patients undergoing salvage chemotherapy followed by ASCT, thereby identifying patients at high risk for posttransplant treatment failure.

CCTG CLC.2/Alliance A041202 demonstrated superior progression-free survival at 2 years with ibrutinib alone (87%; HR 0.39) or ibrutinib-rituximab (IR 88%; HR 0.38) compared to chemo-immunotherapy with bendamustine-rituximab (BR 74%) in treatment-naïve patients (pts) with chronic lymphocytic leukemia (CLL) who were 65 or older (Woyach NEJM 2018). We hypothesized that ibrutinib-based therapies would be more costly than BR but that costs would be offset by less toxicity and improved quality of life (QOL). We completed a prospective trial-based economic analysis to study the direct medical costs and quality-adjusted benefit associated with ibrutinib-based therapies compared to BR in the Canadian (CDN) subset of patients enrolled in CLC.2/Alliance 041202. All CDN pts were invited to participate in the companion analysis. Health utilities were collected using the EuroQOL EQ-5D and calculated using CDN population valuations (Bansback PLOS One 2012). Resource utilization forms were administered to collect off-protocol health care encounters. The planned analysis was a cost-utility analysis from the perspective of a public healthcare system, examining the costs and outcomes (quality-adjusted life years or QALYs) of ibrutinib-based therapy compared to BR. Unit costs were applied to resource data based on publicly available provincial/national databases; all costs were expressed in 2019 US dollars (1 CDN = 0.75 US dollar). Total and disaggregated direct medical costs are presented descriptively. Mean survival was calculated using the restricted mean survival method from randomization to the study time-horizon of 24 months; derived utilities were used to calculate QALYs. A discount rate for costs and benefits (r=0.05) was applied. The analysis was based on estimation (with bootstrapping) of an incremental cost-effectiveness ratio (ICER) and/or direct medical costs. A total of 55 pts were enrolled; two pts who did not receive any treatment were censored at day 1 and 3 after randomization and excluded from analysis. Of the 53 analysed, pt demographics were well balanced between treatments and were reflective of the entire population: mean age was 71.6 (SD 6.34) in pts receiving ibrutinib alone (n=17), 72.2 (SD 3.85) in pts receiving IR (n=18), and 71.7 (SD 4.1) in pts receiving BR (n=18). A total of 3 pts, one in each arm, had 17p deletion. Progression-free survival at 2 years for CDN pts was 94% (95% CI 65-99%) for ibrutinib, 100% (95% CI 100-100%) for IR, and 72% (95% CI 45-87%) for BR (Figure 1). At 24 months, 1 pt on the BR arm had crossed over to ibrutinib (as per protocol); there was no overall survival difference between the three arms. On-protocol costs (including protocol treatment, ambulatory care, and imaging) and off-protocol costs (including hospitalizations, concomitant medications, and ambulatory care) are highlighted in Figure 2. On-protocol costs were higher for pts receiving ibrutinib (mean $142,001 USD; SD 48,417) and IR ($164,931; SD 46,208) compared to BR ($38,509; SD 10,351), driven by higher drug acquisition costs associated with ibrutinib (list price $6422 for 420mg/30 days). In contrast, off-protocol costs were modestly higher for pts on BR (mean $3050; SD 3812) compared to the ibrutinib ($2460; SD 3863) or IR ($2890; SD 4206); hospitalizations were the key off-protocol cost drivers and were highest for pts on IR and BR. Overall mean costs over the 2-year time horizon were $144,461 (SD 47,910) for pts on ibrutinib, $167,820 (SD 46,830) for pts on IR, and $41,560 (SD 11,849) for pts on BR. Discounted QALYs were similar between the three treatment arms: 1.66 (0.16) for ibrutinib alone, 1.65 (0.24) for IR, and 1.66 (0.17) for BR. Given the similar quality-adjusted survival between arms at the time of this analysis, a formal ICER was not calculated. Direct medical costs are substantially higher for pts receiving continuous ibrutinib-based therapies, compared to chemo-immunotherapy of fixed duration, in frontline CLL management; the key cost driver is the cost of ibrutinib. The PFS benefit with ibrutinib-based therapy has not translated into an advantage in quality-adjusted survival to date; further follow-up may be required to demonstrate any cost or QOL benefits associated with fewer progression events for those on ibrutinib. Support: U10CA180821, U10CA180882; U10CA180863 and #704970 CCTG. https://acknowledgments.alliancefound.org ClinicalTrials.gov: NCT01886872 Figure Disclosures Owen: AbbVie, F. Hoffmann-La Roche, Janssen, Astrazeneca, Merck, Servier, Novartis, Teva: Honoraria. Lam:Roche: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau. Crump:Servier: Consultancy; Kite/Gilead: Consultancy; Roche: Consultancy. Sperlich:Lundbeck Canada: Honoraria. Woyach:Pharmacyclics, Janssen, Morphosys, Karyopharm, Verastem, Abbvie, Lox: Research Funding; Janssen, Pharmacyclics, AstraZeneca, Abbvie, Arqule: Consultancy; Pharmacyclics LLC, an AbbVie Company, AbbVie, Janssen, AstraZeneca, ArQule: Honoraria. Prica:astra zeneca: Honoraria; seattle genetics: Honoraria; Gilead: Honoraria. Hay:Roche: Research Funding; Janssen: Research Funding.

Introduction: Previous studies have demonstrated that frailty is associated with mortality among patients with non-Hodgkin lymphoma including diffuse large B-cell lymphoma (DLBCL). However, no studies have examined frailty in an unselected population-based sample of patients with DLBCL, nor have data on health care utilization been considered as a potential mediator of this relationship. Objective: To determine whether frailty is associated with one-year survival in an unselected population of patients with DLBCL, and examine whether its impact is mediated by health care utilization during chemotherapy treatment. Methods: A retrospective cohort study was conducted using population-based health care data in Ontario, Canada. Patients >65 years diagnosed with DLBCL or transformed follicular lymphoma between January 2006 and December 2017 and receiving first-line chemo-immunotherapy were included. Frailty was defined by modifying a previously validated score developed for use with population-based data in Ontario, comprising 30 multidimensional variables (McIsaac, Ann Surg. 2019;270(1):102-108). Patients were categorized as "frail" (score >0.21) vs. "non-frail" (score ≤0.21). Covariates included age, number of comorbidities based on the Johns Hopkins Aggregated Diagnosis Groups (ADGs), and health care utilization during chemotherapy (defined as emergency department (ED) visit or inpatient hospitalization not resulting in death during treatment, and analysed as a time-varying covariate). Cox regression was performed to examine the association between frailty and one-year mortality (primary outcome). Secondary outcomes included health care utilization, chemo-immunotherapy exposure, and cause of death. Results: 5,527 patients were included in the study. 5,216 patients (94%) had de novo DLBCL, and 311 (6%) of patients had transformed follicular lymphoma. The median age was 75 years (IQR 70-80), and 48% (N=2672) were female (Table 1). 2,699 (49%) of patients were classified as frail (Table 2). Frail patients tended to be older (median age 76 (IQR 71-81) vs. 74 years (IQR 70-79)). The difference in mortality between frail and non-frail patients was most pronounced in the initial year following start of treatment (Figure 1a). Within 90 days of first-line rituximab, 14% (N=370) of frail vs. 7% (N=185) of non-frail patients had died (p The relationship between frailty and survival remained consistent when measured in quartiles (HR 1.6 (95% CI 1.3-1.9) for Q2, 2.0 (95% CI 1.7-2.4) for Q3, 2.7 (95% CI 2.3-3.2) for Q4, p Conclusion: Frailty is significantly associated with one-year mortality in patients with newly diagnosed DLBCL, even after adjusting for age, comorbidities, and health care utilization. Frailty appears to be associated with poor tolerability of chemotherapy and a higher likelihood for requiring acute hospital-based care, and future analyses will explore whether this is related to patients suffering increased treatment-related toxicity. Future analyses of these data will also address whether frail patients who die within one-year of first-line treatment have different clinical characteristics compared to frail patients who survive beyond one year. Future prospective studies may help clinicians understand whether any frailty-related variables are modifiable and the role of alternative treatment strategies for vulnerable patients. Disclosures Prica: astra zeneca: Honoraria; seattle genetics: Honoraria; Gilead: Honoraria.

INTRODUCTION: The Alliance A041202/ CCTG CLC.2 trial demonstrated superior progression-free survival with ibrutinib-based therapy compared to chemoimmunotherapy with bendamustine-rituximab (BR) in previously untreated older patients with chronic lymphocytic leukemia (CLL). We completed a prospective trial-based economic analysis of Canadian patients to study the direct medical costs and quality-adjusted benefit associated with these therapies. METHODS: Mean survival was calculated using the restricted mean survival method from randomization to the study time-horizon of 24 months. Health state utilities were collected using the EuroQOL EQ-5D instrument with Canadian tariffs applied to calculate quality-adjusted life years (QALYs). Costs were applied to resource utilization data (expressed in 2019 US dollars). We examined costs and QALYs associated ibrutinib, ibrutinib with rituximab (IR), and BR therapy. RESULTS: A total of 55 patients were enrolled; two patients were excluded from the analysis. On-protocol costs (associated with protocol-specified resource use) were higher for patients receiving ibrutinib (mean $189,335; p

Purpose To determine the relationship of PET/CT staging to the management and outcomes of participants with apparent limited-stage (LS) Hodgkin lymphoma (HL) or aggressive non-HL (ANHL) treated with curative intent. Materials and Methods This prospective multicenter registry included 850 participants (467 men and 383 women; median age, 54.1 years) from nine centers who had LS HL or ANHL on the basis of clinical data and CT, or with equivocal CT for advanced stage, who were considered for curative-intent first-line therapy. Participants were recruited between May 1, 2013, and December 31, 2015. Pre-PET/CT treatment plan was compared with treatment provided. Survival and second-line therapy initiation were compared with an historical control pool staged by using CT alone. Administrative data sources were used to control for baseline characteristics. Outcomes were assessed by using adjusted Cox proportional hazards regression and propensity score matching. Results PET/CT helped to upstage 150 of 850 participants (17.6%). There was a change in planned therapy in 224 of 580 (38.6%) of participants after PET/CT. There was a lower 1-year mortality for participants with ANHL in the PET/CT versus CT cohort (hazard ratio, 0.63; 95% confidence interval: 0.40, 1.0; P < .05) and for those with LS at PET/CT compared with those with LS at CT (hazard ratio, 0.40; 95% confidence interval: 0.21, 0.74; P = .004). For participants with HL, no 1-year outcome difference was found (P = .16). Conclusion PET/CT helped to upstage approximately 18% of participants and planned management was frequently altered. Participants with aggressive non-Hodgkin lymphoma whose first-line therapy was guided by PET/CT had significantly better survival compared with participants whose treatment was guided by CT. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Scott in this issue.

Guillain-Barré syndrome (GBS) is a rare condition caused by autoimmune damage of peripheral nerves. We describe a case where a man in his 80s presented with subacute, progressive fatigue and weakness. He had received an outpatient work-up for possible haematological malignancy, but eventually presented to the emergency department for worsening weakness. A physical exam and cerebrospinal fluid analysis suggested a diagnosis of GBS. Subsequently, a pathological diagnosis of angioimmunoblastic T-cell lymphoma was made. The patient underwent intravenous immunoglobulin treatment for GBS and was started on cyclophosphamide, doxorubicin, vincristine and prednisone therapy. Prior research has suggested that incident malignancy may be associated with GBS, which may be caused by a paraneoplastic-type phenomenon, malignancy-associated immune dysregulation or an autoimmune reaction triggered by a common exposure. Clinicians should be aware of the possible association between these two conditions and should remain open minded to the possibility of non-infectious triggers for GBS.

Background: The use of virtual care rapidly increased during the COVID-19 pandemic to provide adequate care for patients while minimizing contact. Studies in solid tumors show high rates of patient satisfaction with virtual care as well as cost-savings. However, little is known about the application of virtual care in malignant hematology, which includes a heterogenous population of patients often at increased risk of infection. Understanding when virtual care or a hybrid model can be used is crucial for comprehensive patient care. Methods: A retrospective review of patients with hematologic malignancies receiving care at Princess Margaret (PM) Cancer Centre in Toronto, Canada from October 2019 to March 2021 was performed. The primary objective was to describe the use of virtual care at three time points: prior to the pandemic, during the initial months of the pandemic, and beyond the initial months. Patients were included in the analysis if they had a clinical visit for their hematologic malignancy. Patients were excluded if they were presenting for treatment-related visits or blood count checks. All methods of virtual care, including phone visits and teleconferencing, were included in the analysis. Patient satisfaction with virtual care was assessed using responses to the Your Voice Matters survey administered from September 2020 to April 2021, a provincial survey of patient-reported experience. Results: A total of 93472 visits for 23162 patients were identified at PM from October 2019 to March 2021 (55% of visits for ambulatory clinic appointments). Mean age was 60 years (range 18-103 years) and 45% of patients were female (N = 23162). Ambulatory clinic appointments for new consultation or follow-up care were done in the following clinics: autologous or allogeneic bone marrow transplant (21%, N = 10 747), cellular therapy (0.2%, N = 82), leukemia (26%, N = 13419), lymphoma (32%, N = 16427) and myeloma (21%, N = 10711). From October 2019 to March 2020, there were 14512 visits, of which nearly 100% were in-person (N = 14511). From March 1 2020 to September 1 2020, there were 19179 total visits, of which 36% were virtual, with the majority of visits by phone (6325 phone visits and 567 video visits). From September 1 2020 to March 1 2021, there was a small decrease in the use of virtual care (p A total of 75 survey responses for patients with hematologic malignancies followed at PM were available. 67 responses (89.3%) were from patients, with the remaining from caregivers. 47 visits (62.7%) were in-person, 26 visits (34.7%) were virtual, and 2 visits (2.7%) did not have the visit type available. Survey results are shown in Table 1.Results for in-person and virtual visits were very similar, with both groups reporting that their provider listened to their concerns and involved them in making treatment decisions. There was a trend toward providers discussing physical symptoms more for patients who had virtual visits (mean score of 4.73/5 for virtual visit compared to a mean score of 4.36/5, p=0.10). Data on next visit type preference was available for 25 patients who had a virtual visit and 46 patients who had an in-person visit. For patients who had a virtual visit, 36% preferred a repeat virtual visit with 56% having no preference and only 7.7% preferring an in-person visit. For patients who had an in-person visit, 33% preferred their next visit to be virtual, with only 24% preferring their next visit to be in-person and the remaining 43% having no preference. Conclusion: The use of virtual care increased substantially during the COVID-19 pandemic and persisted into 2021 with high rates of patient and provider satisfaction. The highest uptake of virtual care was for patients with myeloma or lymphoma. There were no significant differences in patient satisfaction scores for virtual visits compared to in-person visits, and one third of patients preferred a virtual visit after an in-person visit. These findings suggest that virtual care is a feasible and preferred tool for delivering care to a substantial proportion of patients with hematologic malignancies. Further work is needed to determine how to optimally integrate virtual care for specific patient populations. Figure 1 Figure 1. Disclosures Prica: Astra-Zeneca: Honoraria; Kite Gilead: Honoraria.

Introduction The presence of deletion 17p or monosomy 17 (del(17p)/-17) detected by fluorescence in situ hybridization (FISH) is well-established as a high-risk (HR) factor in multiple myeloma (MM). The del(17p)/-17 clone size and the clinical impact in patients that have ≥60% involved nuclei is controversial. Optimal treatment is also controversial, with tandem autologous stem cell transplantation (ASCT) explored but not uniformly adopted in the real world (ENM02, StaMMina). At our center, we have routinely offer tandem transplantation for del(17p)/-17 and now review our experience over a 10-year period, including the significance of del(17p)/-17 genetic variations on outcomes. Methods We performed a retrospective chart review of all patients identified with del(17p)/-17 patients who were offered tandem transplant and underwent at least one ASCT at Princess Margaret Cancer Centre from 2009-2019. Patient and disease characteristics, responses, and survival outcomes were collected from the Myeloma and Transplant databases and electronic patient records under REB approval. Results Patient, disease, and treatment characteristics. We identified 100 patients with del(17p)/-17 who underwent ASCT at our center. These patients were separated into three groups: those with a deletion of the TP53 locus (57%), those that had monosomy 14 (17%), and those with a relative loss the TP53 locus (eg. aneusomy or polyploidy,13%). The median % of nuclei with del(17p) was 39% (range 5-93%), with 27 (25%) over 60%. 28% of patients carried at least one other cytogenetic abnormality besides del(17p), most commonly t(4;14). All patients were intended for tandem transplant, but only 69 (69%) completed both transplants. Reasons for not proceeding to a second transplant were: patient declined (29%), toxicity (26%), clinical trial (19%), progression prior to the second transplant (13%), with one early death (3%). Median age at transplant was 61 years (range 40-72); most were male (61%) with advanced R-ISS II and III (97%). The most common induction regimen used was cyclophosphamide, bortezomib and dexamethasone (CYBORD)(87%), with 10% requiring a 2 nd induction regimen for inadequate response/progression. Standard conditioning was melphalan 200mg/m 2 for both first and second transplants. Median time from diagnosis to first ASCT was 5.9 months (range 3-24) and time from first to second transplant was 3.3 months (range 1-7). Most patients (90; 84%) received maintenance therapy post-transplant: 47% lenalidomide, 29% multiple agents (commonly lenalidomide and a proteasome inhibitor) Response and survival outcomes After induction, the rate of VGPR (very good partial response) or greater was 53%, increasing to 73% after 1 st ASCT, 85% after 2 nd ASCT. At a median follow-up of 32 months (range 3-130), the median PFS for all patients was 39.2 months 95% CI (24.1-46) and median OS was not yet reached (NYR) (95% CI 57.9-NYR). When analyzed by whether single or tandem transplant was performed, median PFS was 21.8 months (95% CI 10.3-43.3) for single ASCT, and 42.1 months (95% CI 32.8-NYR) for tandem ASCT (P=0.0096). The median OS was 57.6 months for single ASCT (95% CI 22.2-86.5), but NYR for tandem ASCT (95% CI 105.6-NYR) (p=0.0022). On subgroup analysis, patients with ≥60% del(17p) achieved a median PFS 45 months (95% CI 14.4-NYR) and median OS 68.5 months (95% CI 20.9-68.5), median was only PFS 24.9 months (95% CI0.4-NYR) and median OS 29.3 months (95% CI 0.4-68.5) for those who received single ASCT. (table1) TP53 signal pattern analysis (table 2) showed the median OS for patients with monosomy 17 was NYR, while it was 105.7 months for patients with deletion, and 86.5 months for those with relative loss. Median PFS was 43.3 months for the monosomy group, 32.8 months for deletion group, and NYR for relative loss. Conclusions Our experience shows that MM patients with del(17p)/-17 appear to have deeper responses and improved outcomes with more aggressive tandem transplantation. However, approximately 1/3 of our patients intended for tandem transplant did not undergo a second transplant, identifying a focus of future investigation and optimization. Our analysis also suggests that clone size of del(17p) >60% does impact OS negatively, but improved with tandem transplantation. The type of deletion also appears to affect outcomes with deletion having worse PFS but not worse OS. Figure 1 Figure 1. Disclosures Prica: Astra-Zeneca: Honoraria; Kite Gilead: Honoraria. Reece: Takeda: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria; Millennium: Research Funding; Sanofi: Honoraria; BMS: Honoraria, Research Funding; Karyopharm: Consultancy, Research Funding; GSK: Honoraria. Trudel: Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Research Funding; BMS/Celgene: Consultancy, Honoraria, Research Funding; Genentech: Research Funding; Roche: Consultancy; Sanofi: Honoraria; Pfizer: Honoraria, Research Funding. Chen: Beigene: Membership on an entity's Board of Directors or advisory committees; Astrazeneca: Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy.

Background: Bendamustine plus rituximab (B+R) was established as a preferred first-line therapy for indolent non-Hodgkin's lymphoma (iNHL) and mantle cell lymphoma (MCL); however, few reports on the performance of this combination in the real-world setting in elderly patients are available to date. Methods: A retrospective review of adult patients over 70 years (elderly) vs younger ( Results: Among 201 assessed patients, 133 were elderly (mean age 77.9 years) and 88 younger (mean age 61.1 years) at time of B+R initiation. Baseline patient characteristics are presented in Table 1. There were more MCL in the elderly group: 20.3% vs 3.2% in the younger group. Significantly more patients in the elderly group had history of second malignancy. Prostate, breast, colon, and bladder cancer were more common in elderly, and lymphoid and thyroid in younger groups. Bulky lymphadenopathy, cytopenia, and constitutional symptoms were the most common indications for B+R initiation both in elderly (74.4%) and younger (79.26%) patients. Median number of B+R cycles was 6 for both groups. Mean dose of bendamustine received was 83.6 mg/m 2 in the elderly vs 88 mg/m 2 in the younger groups (p=0.0001). Full doses of bendamustine were given in 54% of elderly patients as compared to 79.5% younger patients. Treatment was delayed in 54% of the elderly and 43.2% of the younger patients. The mean delay time was similar in both groups: 20.1 [7-147] vs 17.1 [7-35 days]. The number of adverse events (AE) per patient was similar between the groups across each cycle (Table 2). Rituximab-associated infusion reactions were the most common adverse events in both groups. One patient in younger group developed prolonged neutropenia, lasting over 15 months. G-CSF support received 12.4% elderly and 22.7% younger patients. Nine patients (8%) in elderly and six patients (6.8%) in younger group (p=0.7604) developed transformed aggressive B-Cell lymphoma. Thirteen patients (11.5%) in elderly and five patients (5.7%) in younger group (p=0.1530) had secondary malignancies. Melanoma, metastatic squamous cell and renal carcinoma were more common in elderly group. Younger patients had metastatic squamous cell carcinoma and renal carcinoma, Kaposi sarcoma, MDS and thyroid cancer. Overall response rate was 91.2% in elderly group vs 98.9% in younger group, including complete remission in 71.7% vs 84.1%. Median follow-up was 42 months [4.0-97.0]. Although median overall survival (OS) was not reached in both groups, it was shorter in elderly compared to younger group (HR 0.24, CI 0.14-0.42, p Conclusion: In the real-world setting elderly patients had more advanced and high-risk disease, as well as higher ECOG status. B+R was associated with greater dose reduction and treatment delays. Adverse events profile and incidence did not differ significantly from the younger group. Response rates were lower, but relapse rate was higher in elderly patients. OS was inferior in elderly patients as compared to the younger group, due to higher rate of relapse and secondary malignancies. Figure 1 Figure 1. Disclosures Prica: Astra-Zeneca: Honoraria; Kite Gilead: Honoraria.

Introduction Outpatient autologous stem cell transplantation (ASCT) has become standard of care in many centres due to limited inpatient resources and rising financial constraints. Outpatient ASCT involves family members/friends assuming patient care responsibilities during the acute transplant period. Although this may be associated with reduced direct medical costs, less is known about the "out of pocket costs" and "lost opportunity costs" to patients and their caregivers, as well as impact on caregiver quality of life (QOL). Outpatient transplantation is perceived to provide superior QOL for patients, but there is little evidence to support this. Thus, our objectives were to compare the QOL of patients and their caregivers undergoing outpatient and inpatient ASCT, and to quantify indirect costs to them. Methods This is a single centre cohort study of patients with lymphoma and multiple myeloma undergoing ASCT at Princess Margaret Cancer Centre from April 2016 - February 2021. Patients without a primary caregiver were still eligible to complete the QOL portion of the study. Patients completed several questionnaires including FACT-BMT, FACT-F, and EQ-5D. Caregiver questionnaires included: Caregiver Quality of Life Index-Care (C-QOLC), and a caregiver self-administered financial expenditure survey (C-SAFE). Total indirect costs were defined as lost opportunity costs (i.e., wages) plus out-of-pocket costs (e.g., parking, accommodations). Questionnaires were completed at 5 time points: D0 (prior to ASCT), D+7, D+14 (discharge from daily visits), D+28 (discharge from ASCT) and D+100 (follow-up). Demographic and clinical characteristics were assessed using descriptive statistics. Pairwise changes in QOL from baseline were assessed using linear mixed models to account for repeated measures with group, age and sex included as fixed effects. Alpha was defined as p Results A total of 97 patients (49 outpatients and 45 inpatients) and 66 caregivers (43 outpatients and 22 inpatients) were enrolled. Patients had a median age of 59 years (range 18-71) and were predominantly male (60%) with 66% diagnosed with multiple myeloma and 34% with lymphoma. Majority of caregivers were spouses (76%). Inpatients were more likely to be employed and have lymphoma. The overall cohort demonstrated a clinically meaningful decrease (≥4 points) from baseline in mean FACT-F scores (fatigue) at D+7, D+14, and D+28 with slight improvements at D+100 (Table 1). Compared to inpatients, outpatients overall exhibited significantly (p=0.011) greater changes in fatigue from baseline at D+7 and D+14, with comparable change scores at D+28 and D+100 between groups (Figure 1a). Moreover, for all patients, there was a clinically meaningful decrease from baseline in mean QOL scores by FACT-BMT (≥4 points) at D+7 and D+14, and a meaningful improvement at D+100, with no differences between groups (Table 1). On the FACT-BMT subscales, outpatients had overall worsening scores compared to inpatients on the Physical (p=0.029), and Functional Well-Being Subscales (p=0.043) (Figure 1c), while no differences were detected on the Emotional and Social Well-being scales. Health utility scores were also calculated from the EQ-5D-3L, with a significant downward trend in the overall sample at D+7; however, no clinically relevant changes (≥ 0.08) were noted, and results were comparable between groups (Figure 1d). With respect to caregiver QOL, there were no differences in mean change scores between the two groups; however overall, caregivers had a significant improvement at D+100 compared to baseline (p Conclusions There was significant deterioration of various measures of QOL in all patients, irrespective of outpatient or inpatient status. Outpatients, however, reported significantly greater changes in fatigue from baseline at D+7, D+14 and D+28. Caregiver QOL appears comparable between the two modalities. The financial burden on caregivers is high, with significantly higher total indirect costs in outpatient caregivers in the acute post-ASCT period. Figure 1 Figure 1. Disclosures Prica: Kite Gilead: Honoraria; Astra-Zeneca: Honoraria. Chen: Astrazeneca: Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy. Crump: Novartis: Membership on an entity's Board of Directors or advisory committees; Kyte/Gilead: Membership on an entity's Board of Directors or advisory committees; Epizyme: Research Funding; Roche: Research Funding. Kridel: Gilead Sciences: Research Funding. Kuruvilla: AbbVie: Honoraria; Incyte: Honoraria; Medison Ventures: Honoraria; Merck: Honoraria; Novartis: Honoraria; Gilead: Honoraria; Seattle Genetics: Honoraria; Karyopharm: Honoraria, Other: Data and Safety Monitoring Board; Roche: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; AstraZeneca: Honoraria, Research Funding; TG Therapeutics: Honoraria; Amgen: Honoraria; Pfizer: Honoraria; BMS: Honoraria; Antengene: Honoraria. Reece: Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; BMS: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Sanofi: Honoraria; Millennium: Research Funding; Karyopharm: Consultancy, Research Funding; Amgen: Consultancy, Honoraria; GSK: Honoraria.