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This study compared the quality-adjusted effectiveness and costs of three treatment options for transplant-eligible patients with early progression (POD24) of follicular lymphoma. A Markov decision-analytic model using a 20-year time horizon was used to compare allogeneic stem cell transplant (alloSCT), autologous stem cell transplant (ASCT), and chemo-immunotherapy (O-CHOP). For second relapse/refractory disease, novel therapy use was modeled, including lenalidomide and rituximab/obinutuzumab, and PI3K inhibitors (PI3Ki). Costs were considered from a Canadian public health payer’s perspective. Probabilistic analyses (10,000 simulations) demonstrated that at a willingness-to-pay threshold of $50,000, ASCT was most cost effective 60% of the time. ASCT resulted in more life years (10.2 vs. alloSCT 9.9 vs. O-CHOP 10.0) and quality-adjusted life years (7.5 vs. alloSCT 6.6 vs. O-CHOP 7.4), with the lowest direct costs ($190,128 CAD). In sensitivity analyses, the model was robust to key variables, including differing probabilities of progression, non-relapse mortality, graft-versus-host-disease (GVHD), costs of treating GVHD, costs of PI3Ki, and probability of secondary malignancy from ASCT. However, if patients were older than 65 years or their life expectancy was less than 10 years, chemo-immunotherapy was the preferred strategy. When considering cost, effectiveness, and toxicities, the preferred treatment strategy for most patients with POD24 follicular lymphoma is ASCT.

•Health care utilization and costs of older frail and nonfrail patients with DLBCL were described, from initial treatment to end-of-life phases.•Frailty was associated with higher adjusted health care utilization and costs across all phases except end of life in which there was no difference between groups.

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.

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.

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.

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.

Autologous stem cell transplant (ASCT) is a feasible treatment option for multiple myeloma (MM) patients with renal insufficiency; however, these patients tend to experience higher rates of drug toxicity and transplant-related mortality (TRM) during ASCT. Recent adoption of bortezomib-based induction regimens and dose reduction of melphalan during conditioning may improve outcomes in this population. In this single center retrospective study, we compared the toxicity and survival outcomes of 96 MM patients with renal insufficiency undergoing ASCT between two eras: 1998–2007 and 2008–2016. The proportion of dialysis dependent patients was similar in both groups (49 and 45%). We found no TRM in those transplanted more recently as compared with 13% in the older era of ASCT. There were significantly more high grade (grades 3–4) toxicities in the older era of ASCT including high grade electrolyte abnormalities, mucositis, delirium, and bleeding. Patients transplanted more recently had significantly higher overall response rate (ORR) as well as deeper responses to ASCT (≥VGPR in 79% vs 39%). Progression-free survival (PFS) was prolonged by 26 months in the more recent era compared with the older era. Overall, improvements in treatment regimens have resulted in reduced TRM and toxicities for patients with renal insufficiency undergoing ASCT.

Several strategies are available for the initial treatment of advanced-stage Hodgkin lymphoma, but the optimal strategy in terms of cost-effectiveness is unclear. The aim of this study was to compare the quality-adjusted effectiveness and costs of five modern treatment options for transplantation-eligible patients with newly diagnosed advanced-stage Hodgkin lymphoma.

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Background:The optimal management of patients with primary mediastinal B-cell lymphoma (PMBCL) who experience a partial metabolic response (PMR) on FDG-PET after initial systemic therapy is unclear. This study aimed to investigate different management strategies and outcomes for PMBCL patients who achieved PMR following primary systemic therapy, utilizing a single-center retrospective design.

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PET/CT affects first-line therapy in a substantial proportion of participants with lymphoma that is aggressive at histologic analysis. Participants with aggressive non-Hodgkin lymphoma whose first-line therapy was guided by PET/CT had better outcome compared with participants whose treatment was guided by CT.

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Buckstein: Novartis: Honoraria; Astex: Honoraria; Celgene: Honoraria; Celgene: Research Funding; Takeda: Research Funding. Prica:seattle genetics: Honoraria; Gilead: Honoraria; astra zeneca: Honoraria. Leber:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS/Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Otsuka Pharmaceutical: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Lundbeck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda/Palladin: Honoraria, Membership on an entity's Board of Directors or advisory committees; Treadwell: Honoraria, Membership on an entity's Board of Directors or advisory committees. Chodirker:Hoffman Laroche: Honoraria. Lin:Novartis: Research Funding; Pfizer: Honoraria. Callum:Octapharma: Research Funding; Canadian Blood Services: Research Funding.

Although most patients (pts) with newly diagnosed stage III or IV Hodgkin lymphoma (HL) will be cured with initial therapy (tx), about 20-25% of pts will have relapsed or refractory (R/R) HL. The standard initial tx for adults with advanced stage HL, doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), is associated with pulmonary toxicity due to bleomycin. Recent studies have demonstrated that in pts with a negative interim PET scan, the omission of bleomycin after 2 cycles is non-inferior with regards to survival. However, a significant proportion of pts have a positive interim PET scan and require escalation to BEACOPP - an effective but toxic regimen associated with secondary malignancies and infertility. Recently, the addition of brentuximab vedotin (BV) to AVD chemotherapy (BV-AVD) demonstrated improved modified and traditionally-defined progression-free survival (PFS) compared to ABVD. However, the BV-AVD regimen was associated with higher rates of neutropenia, sepsis, and peripheral neuropathy compared to ABVD, and there still was a ~20% failure rate. In adolescent and young adult pts with advanced stage HL, there is a similar ~20% failure rate using ABVE-PC (AB, vincristine, etoposide, prednisone, cyclophosphamide) and response-adapted radiation therapy (RT) - with RT use in a majority of pts. There remains room to improve outcomes in pediatric and adult pts with newly diagnosed advanced stage HL.

Chavez: Morphosys: Consultancy, Speakers Bureau; Merck: Research Funding; Bayer: Consultancy; BeiGene: Speakers Bureau; Karyopharm: Consultancy; AbbVie: Consultancy; Genentech: Speakers Bureau; AstraZeneca: Speakers Bureau; Gilead: Consultancy; Verastem: Consultancy; Epizyme: Speakers Bureau; Celgene: Consultancy; Novartis: Consultancy; Kite, a Gilead Company: Consultancy, Speakers Bureau; Pfizer: Consultancy. William:Dova: Research Funding; Seattle Genetics: Research Funding; Incyte: Research Funding; Merck: Research Funding; Kyowa Kirin: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Guidepoint Global: Consultancy. Brammer:Celgene Corporation: Research Funding; Seattle Genetics, Inc.: Speakers Bureau. Smith:Pharmacyclics: Research Funding; Genentech/Roche: Consultancy, Other: Support of parent study and funding of editorial support, Research Funding; Acerta: Research Funding; BMS: Consultancy; Karyopharm: Consultancy, Research Funding; TG Therapeutics: Consultancy, Research Funding; FortySeven: Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy. Prica:astra zeneca: Honoraria; seattle genetics: Honoraria; Gilead: Honoraria. Zain:Kyowa Kirlin: Research Funding; Mundai Pharma: Research Funding; Seattle Genetics: Research Funding. Glenn:Genentech: Research Funding. Mehta-Shah:Verastem: Research Funding; Karyopharm Therapeutics: Consultancy; Kyowa Kirin: Consultancy; Innate Pharmaceuticals: Research Funding; Celgene: Research Funding; Genetech: Research Funding; C4 Therapeutics: Consultancy; Bristol Myers-Squibb: Research Funding. Boutrin:Astrazeneca: Current Employment, Current equity holder in private company. Zhao:Astrazeneca: Current Employment, Current equity holder in private company. Cheng:Astrazeneca: Current Employment, Current equity holder in private company. Standifer:Astrazeneca: Current Employment, Current equity holder in private company. Carlesso:Astrazeneca: Current Employment, Current equity holder in private company. Siu:Shatthucks: Research Funding; Symphogen: Consultancy, Research Funding; Tessa: Consultancy; Treadwell Therapeutics: Consultancy, Current Employment; Pfizer: Research Funding; Voronol: Consultancy; Rubius Therapeutics: Consultancy; Abbvie: Research Funding; Agios: Current equity holder in publicly-traded company; Arvinas: Consultancy; Astellas: Research Funding; AstraZeneca: Consultancy, Research Funding; Bayer: Research Funding; Boerhinger-Ingelheim: Research Funding; Bristol-Myers Squibb: Research Funding; Glaxo Smith Kline: Research Funding; Intensity Therapeutics: Research Funding; Navire: Consultancy; Novartis: Research Funding; Oncorus: Consultancy; Mirati: Consultancy, Research Funding; Roche/Genentech: Consultancy; Relay Therapeutics: Consultancy; Roche: Consultancy; Merck: Consultancy.

Background:T-follicular helper (TFH) cells are a novel CD4+ T-cell subset that participates in germinal center maintenance/proliferation. Proliferation of TFHis a postulated mechanism of pathogenesis for T-cell lymphomas (AITL, PTCL and others). The inducible T-cell costimulator (ICOS) is highly expressed in TFHand hence in AITL, PTCL FH type, and some cutaneous T cell lymphomas (CTCL) and follicular lymphomas (FL). MEDI-570 is a human afucosylatedIgG1 kappa monoclonal antagonistic antibody directed against ICOS, which binds to and eliminates ICOS expressing cells in preclinical in vivo models. We investigate the safety, pharmacokinetics (PK) and clinical activity of ICOS blockade by MEDI-570 in T-cell lymphomas.

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.

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Background:Frailty is common in older patients with lymphoma. However, it remains unknown whether frailty is prevalent in patients included in clinical trials of lymphoma, as those with frailty may meet inclusion criteria of a trial which do not include functional information beyond performance status (PS). Understanding the prevalence and impact of frailty in clinical trials is important to direct future stratification criteria, as well as to have robust data to counsel frail patients on their potential outcomes.

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Background:A variety of frontline treatment regimens exist for early-stage unfavourable Hodgkin lymphoma (HL), offering personalization of risk versus benefit in this primarily young population of patients. While radiation therapy has been a mainstay of treatment due to improved progression-free survival (PFS), recent studies have challenged this paradigm, using a PET-driven approach (HD17) or incorporating novel agents (nivolumab-AVD (N-AVD), brentuximab-AVD (A-AVD)). Long term risks of radiation and chemotherapy include secondary breast and other cancers, and heart failure; however novel regimens are more costly with uncertainty surrounding long-term efficacy.

Introduction:Peripheral blood samples of healthy individuals may harbour detectable mutations in genes recurrently mutated in myeloid malignancies, a situation referred to as clonal hematopoiesis (CH). Risk factors for CH include increasing age as well as previous exposure to cytotoxic therapy. CH has been associated with an increased risk of overall mortality, including in the setting of autologous stem cell transplantation (ASCT) for non-Hodgkin lymphoma (Gibson et al, JCO, 2017). The excess mortality is largely driven by cardio-vascular disease, but may also be additionally attributable to an increased risk of myeloid malignancies that arise through the selection of CH subclones. Herein, we aimed to investigate the prognostic implications of CH after ASCT in an independent and diversified, large cohort of lymphoma patients using ultra-deep, highly sensitive error-correction sequencing.