Search

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 : Glofitamab (RG6026) is a novel T-cell-engaging, bispecific, full-length antibody with a 2:1 molecular configuration that facilitates bivalent binding to CD20 on B-cells, and monovalent binding to CD3 on T-cells. Preclinically, glofitamab had superior potency compared with other tested bispecifics with 1:1 formats (Bacac, et al. Clin Cancer Res 2018). NP30179 (NCT03075696) is an ongoing multicenter, Phase I/Ib, dose-escalation and dose-expansion trial evaluating the safety, tolerability, pharmacokinetics, biomarker responses, and efficacy of glofitamab in patients (pts) with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL). Clinical data from NP30179 demonstrated that fixed dosing of glofitamab (0.6-25mg) induced high and durable complete responses with a manageable safety profile in pts with heavily pre-treated R/R NHL (Dickinson, et al. EHA 2020). Obinutuzumab pretreatment (Gpt) was shown to be effective in mitigating the risk of cytokine release syndrome (CRS), allowing for rapid escalation of glofitamab to clinically active doses (Dickinson, et al. EHA 2020). Step-up dosing of glofitamab was used in addition to Gpt to further reduce the risk of CRS. For the first time, we present clinical data of glofitamab step-up dosing with Gpt in pts with R/R NHL. Methods: Pts received 1000mg obinutuzumab 7 days prior to first glofitamab administration. Glofitamab was given intravenously with step-up dosing on Cycle (C) 1 Day (D) 1 and 8 and then at the target dose from C2D1, every 3 weeks for up to 12 cycles (2.5/10/16mg or 2.5/10/30mg). Response rates reported are based on the Lugano criteria (Cheson, et al. J Clin Oncol 2014). Results: As of April 17, 2020, 38 pts received step-up doses of glofitamab; 17 pts received 2.5/10/16mg, and 21 pts received 2.5/10/30mg. Twenty-eight pts (73.7%) had aggressive NHL (aNHL) histologies and ten pts had indolent NHL (iNHL; Table). The median age was 68 years (range 52-85) and median number of prior lines of therapy was 3 (range 1-12). Twenty-seven (71.1%) pts were refractory to their last therapy, and 28 (73.7%) pts were refractory to prior CD20 therapy. After a median follow-up of 2.8 months, across all efficacy-evaluable pts (n=32) the overall response rate (ORR) and complete metabolic response (CMR) rate was 62.5% and 40.6%, respectively. For pts with aNHL (n=24), the ORR was 50.0% with CMR rates of 29.2%. As of the data cut-off date, 17 pts with aNHL (70.8%) had reached the first response assessment only (C3) and remain on treatment; four pts (16.7%) had reached the second response assessment (C6). For pts with iNHL (n=8), the ORR was 100.0% with 75.0% of pts achieving CMR. Across the safety-evaluable population (n=38), the most common AEs were CRS (57.9%), pyrexia (31.6%), neutropenia, thrombocytopenia and hypophosphatemia (28.9% each). No AEs led to treatment discontinuation. Of 22 patients who experienced CRS events, the CRS events only occurred in C1 and C2; 15 had CRS after the 2.5mg dose, 12 after the 10mg dose, and 5 during C2 (16 or 30mg dose; Figure). Eight pts (21.1%) and 13 pts (34.2%) experienced Grade (Gr) 1 and 2 CRS, respectively; none experienced Gr 3 CRS. One pt (2.6%) experienced Gr 4 CRS after the 30mg dose. No CRS events occurred after C2. Tocilizumab was used to manage CRS in six (15.8%) pts: n=2 for 2.5/10/16mg and n=4 for 2.5/10/30mg cohorts. CRS events were manageable and resolved for 21 pts (95.4%) at data cut-off. No Gr ≥3 neurologic adverse events were reported. Consistent with prior biomarker data from fixed-dose regimens (Bröske, et al. EHA 2020), glofitamab administered with step-up dosing induced a transient T-cell redistribution. Conclusions: Step-up dosing of glofitamab allowed escalation up to 30mg to maximize efficacy, while minimizing the risk of increased CRS. High ORR and CMR rates were observed in pts with NHL who had failed several lines of treatment. Toxicity was manageable with the main safety signal being low-grade CRS observed in early cycles. Updated results will be presented at the congress which will include data from at least 50 pts receiving glofitamab step-up dosing with Gpt. Disclosures Hutchings: Genmab, F. Hoffmann-La Roche, Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene, Genmab, Janssen, Novartis, F. Hoffmann-La Roche, Takeda: Research Funding. Carlo-Stella:Servier, Novartis, Genenta Science srl, ADC Therapeutics, F. Hoffmann-La Roche, Karyopharm, Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics and Rhizen Pharmaceuticals: Research Funding; Bristol-Myers Squibb, Merck Sharp & Dohme, Janssen Oncology, AstraZeneca: Honoraria; Boehringer Ingelheim and Sanofi: Consultancy. Bachy:Roche, Gilead: Consultancy; Amgen: Research Funding; Roche, Celgene, Amgen, Janssen, Gilead, Novartis, Sanofi: Honoraria; Beigene: Membership on an entity's Board of Directors or advisory committees. Morschhauser:F. Hoffmann-La Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Epizyme: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Servier: Consultancy; Genentech, Inc.: Consultancy. Crump:Kite/Gilead: Consultancy; Roche: Consultancy; Servier: Consultancy. Iacoboni:Novartis, Gilead, Celgene, Roche: Honoraria. Sureda Balari:BMS: Speakers Bureau; Roche: Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Speakers Bureau; Incyte: Consultancy; Gilead/Kite: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Merck Sharpe and Dohme: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria. Martinez-Lopez:Novartis: Consultancy; Janssen: Consultancy, Honoraria; BMS: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Janssen-cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Lundberg:F. Hoffmann-La Roche: Current Employment, Current equity holder in publicly-traded company. Dixon:Roche Products Limited: Current Employment; F. Hoffmann-La Roche: Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months. Perez Callejo:F. Hoffmann-La Roche: Current Employment, Current equity holder in publicly-traded company. Relf:Roche Products Ltd: Current Employment. Carlile:AstraZeneca: Current equity holder in publicly-traded company, Ended employment in the past 24 months; F. Hoffmann-La Roche: Current Employment, Current equity holder in publicly-traded company. Piccione:Genentech, Inc.: Current Employment; F. Hoffmann-La Roche: Current equity holder in publicly-traded company. Humphrey:F. Hoffmann-La Roche: Current Employment, Current equity holder in private company, Current equity holder in publicly-traded company. Dickinson:Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; Merck Sharp & Dohme: Consultancy. OffLabel Disclosure: Glofitamab (RG6026; CD20-TCB) is a full-length, fully humanized immunoglobulin G1 (IgG1) bispecific antibody with a 2:1 molecular format that facilitates bivalent binding to CD20 on B-cells, and monovalent binding to CD3 on T-cells. Glofitamab redirects T cells to engage and eliminate malignant B cells. Glofitamab is an investigational agent.

Introduction: Burkitt lymphoma (BL) is an aggressive B cell lymphoma with a distinct morphology, immunophenotype and characteristic C-MYC gene rearrangement. When treated with intensive chemotherapy, outcomes are excellent with a reported overall survival of greater than 80% at 3 years. A small subset of patients have primary refractory or relapsed disease, but there have been few reports of treatment and outcomes of these patients due to the rarity of this lymphoma and its otherwise good prognosis. Objective: The objective of this study was to review the characteristics, treatments and outcomes of patients with relapsed/refractory BL. Methods: We included patients 18 years or older with a pathologically confirmed BL diagnosed between 2003 and 2018 at eight Canadian centres who received curative intent frontline chemotherapy and who had primary refractory or relapsed disease. Data were retrospectively reviewed at each site independently. Staging and response assessment was based on computed tomography (CT). Descriptive statistics were used for baseline characteristics and treatment regimens. Kaplan Meier Survival Analysis was used to estimate overall survival (OS) which was calculated from time of relapse. Results: A total of 74 patients were included in the study. Median age was 48 years (IQR 32-61) and 81% were male. Nine patients (12%) were known to be HIV positive. Most patients had advanced disease with stage III/IV (n=47, 64%), bone marrow involvement (n=32, 43%) and at least one extranodal site (n=67, 91%). Nineteen patients (26%) had central nervous system (CNS) involvement at diagnosis. The most common induction regimen was CODOX-M-IVAC (n=43, 58%) followed by CHOP or EPOCH (n=14, 19%) and hyperCVAD (n=7, 9%). Forty five (61%) patients received rituximab with their first line treatment. The median time to relapse from diagnosis was 5 months with a majority of cases being primary refractory (n=57, 77%). Patients had systemic relapse (n=44, 59%), isolated CNS relapse (n=19, 26%) or both (n=11, 15%). Forty three (58%) patients received second-line salvage chemotherapy while 28 (39%) were treated with palliative oral chemotherapy and/or radiation. A variety of salvage regimens were used including systemic and CNS-directed second line regimens: most common GDP (n=7, 9%), hyperCVAD (n=5, 7%) and DHAP (n=5, 7%). Rituximab was given at relapse to 23 patients (31%). Progressive disease during or after salvage was noted in 23 (31%) patients. Twenty patients received a second-line transplant (15 autologous, 5 allogeneic). The median OS of the whole cohort was 3.2 months and 2 year OS was 17.2% (95% CI 9.4-26.9). Median OS for patients receiving salvage was 5.4 months compared to 1.3 months for those who received palliative therapy (p Conclusion: Relapsed/refractory BL has very poor prognosis, even in the rituximab era. There is no standard approach to salvage treatments in this population. Despite advances in novel agents and cellular therapies in aggressive lymphoma, patients with BL are often excluded from these clinical trials. This study highlights the need for inclusion of this population in trials evaluating novel therapies for aggressive B cell lymphomas. Figure 1 Figure 1. Disclosures Gerrie: Astrazeneca: Honoraria, Research Funding; Sandoz: Honoraria; Roche: Research Funding; AbbVie: Honoraria, Research Funding; Janssen: Honoraria, Research Funding. Chua: Merck: Honoraria; Pfizer: Honoraria; Eisai: Honoraria; Gilead: Honoraria. Stewart: Roche: Honoraria; Janssen: Honoraria; Abbvie: Honoraria; Gilead: Honoraria; Celgene: Honoraria; Novartis: Honoraria; AstraZeneca: Honoraria; Amgen: Honoraria; Sandoz: Honoraria; Teva: Honoraria. Kuruvilla: Seattle Genetics: Honoraria; TG Therapeutics: Honoraria; Medison Ventures: Honoraria; Amgen: Honoraria; Karyopharm: Honoraria, Other: Data and Safety Monitoring Board; Gilead: Honoraria; Pfizer: Honoraria; Incyte: Honoraria; AstraZeneca: Honoraria, Research Funding; AbbVie: Honoraria; Antengene: Honoraria; Merck: Honoraria; Novartis: Honoraria; Roche: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; BMS: Honoraria. 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.

Background: MCL is an aggressive non-Hodgkin lymphoma (NHL) subtype and pts with progressive disease (PD) after BTKi therapy have a poor prognosis (Martin et al. Blood 2016). Glofitamab is a T-cell-engaging, CD20xCD3 bispecific antibody with a novel 2:1 molecular configuration with bivalency for CD20 on B cells and monovalency for CD3 on T cells. Glofitamab with obinutuzumab pretreatment (Gpt) has shown promising efficacy with frequent, durable complete responses (CR) and manageable tolerability with fixed dosing (NCT03075696; Dickinson et al. EHA 2020) and step-up dosing (SUD; Hutchings et al. J Clin Oncol 2021) in NHL. Glofitamab and obinutuzumab compete for binding to CD20 receptors; as a result, Gpt reduces the receptor occupancy (RO) of glofitamab. Pts with MCL have a 2-fold higher clearance of obinutuzumab vs other NHL histologies (Gibiansky et al. CPT Pharmacometrics Syst Pharmacol 2014), leading to lower obinutuzumab concentrations and higher glofitamab RO at the start of glofitamab treatment (Djebli et al . Blood 2020). A higher dose of Gpt prior to glofitamab SUD may therefore further reduce the risk of cytokine release syndrome (CRS) in MCL. We report preliminary data from the NP30179 Phase I/II trial in pts with R/R MCL who received a 1000mg or 2000mg dose of Gpt prior to glofitamab monotherapy. Methods: All pts received Gpt 7 days prior to the first glofitamab dose. Intravenous glofitamab SUD was given on days 1 and 8 of Cycle (C)1, then at the target dose from C2 day (D)1 (from C3D1 for SUD starting at 0.5mg), every 3 weeks for up to 12 cycles (0.5/2.5/10/30, 2.5/10/16 or 2.5/10/30mg after 1000mg Gpt, or 2.5/10/30mg after 2000mg Gpt). Pts on fixed dosing received glofitamab (0.6, 16 or 25mg) after 1000mg Gpt from C1 for up to 12 cycles. Response rates are based on the Lugano criteria (Cheson et al. J Clin Oncol 2014). Results: As of May 18, 2021, 29 pts had received glofitamab: fixed dosing after 1000mg Gpt (n=3); SUD after 1000mg Gpt (n=7; 1 pt received SUD starting at 0.5mg) or 2000mg Gpt (n=19). Median age was 69 years (range, 41-84; 69% male), 83% of pts had Ann Arbor Stage III-IV disease and 62.1% had MCL international prognostic index score ≥6 at study entry. Median prior lines of therapy was 3 (range, 1-6), 69% (n=20) had prior BTKi therapy and 14% (n=4) had prior lenalidomide therapy. Many pts were refractory to their first line of therapy (52%; n=15) and/or their last prior therapy (69%; n=20). Median time since last therapy was 1.7 months (range, 0.1-107.5). In efficacy-evaluable pts (n=21), the overall response rate was 81.0% (n=17) and complete metabolic response rate was 66.7% (n=14; Table 1). Similar response rates were observed in pts who had received prior BTKi therapy vs pts who had not (Table 2). Median duration of CR follow-up was 2.4 months (range, 0.0-25); 85.7% (12/14) pts with a CR remained in remission at the data cut-off (median duration of response and median duration of CR were not reached). In safety-evaluable pts (n=29), the most common adverse events (AEs) were CRS (58.6%) and infusion-related reactions (24.1%). All CRS events were Grade (Gr) 1-2 (by ASTCT criteria), except for 1 Gr 4 CRS in the 1000mg Gpt + SUD cohort (3.4%; pt died due to cardiopulmonary insufficiency as a result of rapid PD; at time of death CRS was persisting). CRS rates were lower in the 2000mg Gpt + SUD cohort (9/19; 47.4%) vs the 1000mg Gpt + SUD (5/7; 71.4%) and 1000mg Gpt + fixed dosing (3/3; 100%) cohorts. Overall, median time to first CRS event and duration of CRS event were 16.8 hrs and 38.8 hrs, respectively. All CRS events were manageable (tocilizumab used in 4 pts, low-flow oxygen in 2 pts) and most resolved at data cut-off. Neurologic AEs occurred in 6 pts (20.7%, all Gr 1 [n=5] or Gr 2 [n=1]). Immune effector cell-associated neurotoxicity syndrome (ICANS)-like AEs occurred in 1 pt (3.4%): Gr 1 confusional state and Gr 2 ataxia, both resolving in 1 day. Tumor flare events occurred in 3 pts (10.3%, all Gr 1 [n=2] or Gr 2 [n=1]). No pts discontinued treatment due to AEs. Three deaths were reported and considered unrelated to study treatment: PD (n=2); cardiac arrest (n=1). Conclusions: Glofitamab SUD as monotherapy after Gpt induced high response rates in pts with MCL, most of whom had failed prior BTKi therapy. CRS rates were manageable and mostly low grade. ICANS-like AEs were infrequent, low grade and resolved within 1 day. No treatment discontinuations due to AEs were observed. Further analyses will be presented. Figure 1 Figure 1. Disclosures Phillips: Genentech: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Consultancy, Research Funding; ADCT, BeiGene, Bristol Myers Squibb, Cardinal Health, Incyte, Karyopharm, Morphosys, Pharmacyclics, Seattle Genetics: Consultancy; AbbVie: Consultancy, Research Funding; AstraZeneca: Consultancy; BMS: Consultancy, Research Funding; Incyte: Consultancy, Other: received travel expenses from Incyte, Research Funding. Dickinson: Celgene: Research Funding; Amgen: Honoraria; Janssen: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Takeda: Research Funding; MSD: Consultancy, Honoraria, Research Funding, Speakers Bureau; Gilead Sciences: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Other: travel, accommodation, expenses, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau. Morschhauser: Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: 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; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; AstraZenenca: Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genmab: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Speakers Bureau; Chugai: Honoraria; Genentech, Inc.: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy. Bachy: Kite, a Gilead Company: Honoraria; Novartis: Honoraria; Daiishi: Research Funding; Roche: Consultancy; Takeda: Consultancy; Incyte: Consultancy. Crump: Kyte/Gilead: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Roche: Research Funding; Epizyme: Research Funding. Trněný: MorphoSys: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Portola: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; 1st Faculty of Medicine, Charles University, General Hospital in Prague: Current Employment; Celgene: Consultancy; Gilead Sciences: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses; Incyte: 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, Other: Travel, Accommodations, Expenses; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Amgen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses. Bartlett: Washington University School of Medicine: Current Employment; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Affimed: Research Funding; Autolus: Research Funding; Bristol-Myers Squibb: Research Funding; Celgene: Research Funding; Forty Seven: Research Funding; Janssen: Research Funding; Kite Pharma: Research Funding; Merck: Research Funding; Millennium: Research Funding; Pharmacyclics: Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding. Zaucha: Takeda: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Roche: Honoraria; Amgen: Honoraria; AbbVie: Honoraria; Janssen: Honoraria. Humphrey: Roche: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Perez-Callejo: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. Lundberg: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. Relf: Roche Pharmaceutical Ltd: Current Employment, Current equity holder in publicly-traded company; F-Star Therapeutics: Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months; Harpoon Therapeutics: Divested equity in a private or publicly-traded company in the past 24 months. Filézac de L'Étang: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. Carlile: AstraZeneca: Current equity holder in publicly-traded company, Ended employment in the past 24 months; F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. Clark: Roche Products Ltd: Current Employment. Carlo-Stella: Sanofi: Consultancy, Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Honoraria; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm Therapeutics: Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria; Janssen Oncology: Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Glofitamab is a full-length, humanized, immunoglobulin G1 bispecific antibody with a 2:1 molecular format that facilitates bivalent binding to CD20 on B-cells, and monovalent binding to CD3 on T-cells. Glofitamab redirects T cells to engage and eliminate malignant B cells. Glofitamab is an investigational agent.

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.

Background: Over a third of pts with 1L DLBCL do not respond to, or relapse after, rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP; [Sarkozy and Sehn. Ann Lymphoma 2019]). Despite recent advances, pts with R/R NHL have limited curative options. Glofitamab (Glofit) is a novel, T-cell-engaging bispecific antibody with a 2:1 molecular configuration that allows bivalent binding to CD20 on B cells and monovalent binding to CD3 on T cells. Unlike other CD20xCD3 bispecific antibodies, this format uniquely enables combination with anti-CD20 antibodies, including rituximab. Glofit monotherapy induces high response rates in R/R B-cell NHL (Hutchings et al. J Clin Oncol 2021). We present results of the ongoing NP40126 study (NCT03467373), designed to assess the feasibility and safety of Glofit + R-CHOP in R/R NHL (dose-escalation phase) and 1L DLBCL (safety run-in phase). Methods: R/R NHL dose-escalation: Pts (Eastern Cooperative Oncology Group performance status [ECOG PS] 0-2) received increasing Glofit doses in separate cohorts (70µg, 1800µg, 10mg and 30mg) plus standard R-CHOP for 6-8 cycles (each 21-day). To mitigate CRS risk, R- or obinutuzumab (G)-CHOP was given in Cycle (C)1, with the aim of tumor debulking. Glofit was given from C2 onwards. For 70µg and 1800µg cohorts, fixed-dose Glofit was given on C2 Day (D)8 and onwards. For 10mg and 30mg cohorts, step-up dosing was used to further mitigate CRS risk (2.5mg C2D8, 10mg C2D15, target dose C3D8 and onwards). Optional Glofit maintenance was permitted (every 2 months for 1L DLBCL safety run-in: Pts (ECOG PS 0-3) received Glofit 30mg plus standard R-CHOP for 6-8 cycles (each 21-day). Pts received R-CHOP in C1; Glofit step-up dosing began in C2 (2.5mg C2D8, 10mg C2D15, 30mg C3D8 and onwards). Response rates were assessed by PET-CT (Lugano criteria; [Cheson et al. J Clin Oncol 2014]). CRS events were graded by ASTCT criteria [Lee et al. Biol Blood Marrow Transplant 2019]. Results: R/R NHL dose-escalation: At data cut-off (June 10, 2021), 31 pts (23 follicular lymphoma [FL]; 6 transformed FL; 1 marginal-zone lymphoma; 1 mantle-cell lymphoma) had received Glofit with R/G-CHOP. Median age was 62 years, median prior lines of therapy was 2 (range: 1-5). In efficacy-evaluable pts (n=31), after a median 9.0 months' (range: 0-29) follow-up, the overall response rate (ORR) was 90% (n=28) and complete response rate (CRR) was 77% (n=24). Median duration of response was not reached. The Figure shows change in tumor size. Grade (Gr) ≥3 adverse events (AEs) occurred in 28 (90%) pts, serious AEs in 21 (68%) pts and CRS in 17 (55%) pts (mostly low grade; majority after the first 2.5mg Glofit dose; Table). One (3%) pt had a Gr 5 AE (COVID-19 pneumonia not related to study treatment). AEs led to Glofit dose modification/interruption in 2 (6%) pts and Glofit withdrawal in 1 (3%) pt. Neurologic AEs (NAEs) occurred in 20 (65%) pts: Gr 1-2 (16 pts, 52%); Gr 3 (4 pts, 13%). Immune effector cell-associated neurotoxicity syndrome (ICANS)-like AEs were uncommon; a serious AE was reported in 1 pt only (Gr 3 epilepsy during the maintenance phase; resolved in 3 days). Neutropenia occurred in 24 (77%) pts. Median dose intensity was 100% for all R-CHOP components. 1L DLBCL safety run-in: At data cut-off, 13 pts were enrolled (safety population); of these, 4 pts received Glofit 30mg with R-CHOP and were efficacy-evaluable. Median age was 68 years, all pts had Ann Arbor Stage 3/4 disease. At interim assessment (C3), CRR was 100% (4/4). Of 13 pts, 1 (8%) had a CRS event (Gr 1 with fever only) after the first 2.5mg Glofit dose; no other CRS events observed. Gr ≥3 AEs occurred in 8 (62%) pts and Gr ≥3 AEs related to Glofit in 1 (8%) pt only. One (8%) pt had a serious AE and 1 (8%) pt had a Gr 5 AE (infusion-related reaction related to rituximab on C1D1). No AEs led to Glofit or R-CHOP dose interruptions. NAEs occurred in 3 (23%) pts (all Gr 1-2; none were ICANS-like). Neutropenia occurred in 6 (46%) pts. Median dose intensity was 100% for all R-CHOP components. Conclusions: Initial data show that Glofit + R-CHOP has tolerable safety in R/R NHL and 1L DLBCL. R-CHOP dose intensity was maintained in all pts. The very low CRS rate and no neurotoxicity in 1L DLBCL may render Glofit particularly suitable for the outpatient setting without the need for hospitalization. Updated data, including end-of-treatment responses from the 1L DLBCL safety run-in phase, will be presented. Figure 1 Figure 1. Disclosures Ghosh: Seattle Genetics: Consultancy, Honoraria, Speakers Bureau; Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding, Speakers Bureau; AbbVie: Honoraria, Speakers Bureau; Karyopharma: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria, Speakers Bureau; ADC Therapeutics: Consultancy, Honoraria; Adaptive Biotech: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria, Research Funding; Genmab: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding, Speakers Bureau; Epizyme: Honoraria, Speakers Bureau; Incyte: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; Genentech: Research Funding. Townsend: Celgene (Bristol-Myers Squibb): Consultancy, Honoraria; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria. Dickinson: Amgen: Honoraria; Celgene: Research Funding; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Research Funding; Gilead Sciences: Consultancy, Honoraria, Speakers Bureau; MSD: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Other: travel, accommodation, expenses, Research Funding, Speakers Bureau. Topp: Celgene: Consultancy, Research Funding; Janssen: Consultancy; Universitatklinikum Wurzburg: Current Employment; Kite, a Gilead Company: Consultancy, Research Funding; Novartis: Consultancy; Roche: Consultancy, Research Funding; Gilead: Research Funding; Regeneron: Consultancy, Research Funding; Macrogeniecs: Research Funding; Amgen: Consultancy, Research Funding. Santoro: Sandoz: Speakers Bureau; Eli-Lilly: Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AstraZeneca: Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Speakers Bureau; Amgen: Speakers Bureau; AbbVie: Speakers Bureau; Roche: Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Eisai: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Speakers Bureau; Sanofi: Consultancy; Arqule: Consultancy, Speakers Bureau; Novartis: Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. 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. Morschhauser: Epizyme: 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; Genentech, Inc.: Consultancy; Genmab: Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Speakers Bureau; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Chugai: Honoraria; Incyte: Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy; AstraZenenca: Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria. Mehta: Kite/Gilead; Roche-Genetech; Celgene/BMS;Oncotartis; Innate Pharmaceuticals; Seattle Genetics;Incyte; Takeda; Fortyseven Inc/Gilead; TG Therapeutics;Merck; Juno Pharmaceuticals/BMS: Research Funding; Seattle Genetics; Incyte; TG Therapeutics: Consultancy; Seattle Genetics; Incyte; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees. Panchal: F. Hoffmann-La Roche Ltd: Current Employment. Wu: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. Barrett: Roche Products Ltd: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Humphrey: Roche: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Qayum: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. Hutchings: Novartis: Research Funding; Janssen: Honoraria, Research Funding; Incyte: Research Funding; Genentech: Honoraria, Research Funding; Celgene: Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Genmab: Consultancy, Honoraria, Research Funding. OffLabel Disclosure: Glofitamab is a full-length, humanized immunoglobulin G1 bispecific antibody with a 2:1 molecular format that facilitates bivalent binding to CD20 on B-cells, and monovalent binding to CD3 on T-cells. Glofitamab redirects T cells to engage and eliminate malignant B cells. Glofitamab is an investigational agent. Rituximab (Rituxan) is a CD20-directed cytolytic antibody indicated for the treatment of adult pts with: relapsed or refractory, low grade or follicular, CD20-positive, B-cell NHL as a single agent; previously untreated follicular, CD20-positive, B-cell NHL in combination with first-line chemotherapy (chemo) and, in pts achieving a CR or PR to a rituximab product in combination with chemo, as single-agent maintenance therapy; non-progressing (including stable disease), low-grade, CD20 positive, B-cell NHL as a single agent after first-line CVP chemo; previously untreated diffuse large B-cell, CD20-positive, NHL in combination with CHOP or other anthracycline-based chemo regimens; previously untreated and previously treated CD20-positive CLL in combination with fludarabine and cyclophosphamide.