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The utility of posttreatment bone marrow biopsy (BMB) histology to confirm complete response (CR) in lymphoma clinical trials is in question. We retrospectively evaluated the impact of BMB on response assessment in immunochemotherapy-treated patients with previously untreated follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) in the phase 3 Study of Obinutuzumab (RO5072759) Plus Chemotherapy in Comparison With Rituximab Plus Chemotherapy Followed by Obinutuzumab or Rituximab Maintenance in Patients With Untreated Advanced Indolent Non-Hodgkin's Lymphoma (GALLIUM; NCT01332968) and A Study of Obinutuzumab in Combination With CHOP Chemotherapy Versus Rituximab With CHOP in Participants With CD20-Positive Diffuse Large B-Cell Lymphoma (GOYA; NCT01287741) trials, respectively. Baseline BMB was performed in all patients, with repeat BMBs in patients with a CR by computed tomography (CT) at end of induction (EOI) and a positive BMB at baseline, to confirm response. Positron emission tomography imaging was also used in some patients to assess EOI response (Lugano 2014 criteria). Among patients with an EOI CR by CT in GALLIUM and GOYA, 2.8% and 4.1%, respectively, had a BMB-altered response. These results suggest that postinduction BMB histology has minimal impact on radiographically (CT)-defined responses in both FL and DLBCL patients. In GALLIUM and GOYA, respectively, 4.7% of FL patients and 7.1% of DLBCL patients had a repeat BMB result that altered response assessment when applying Lugano 2014 criteria, indicating that bone marrow evaluation appears to add little value to response assessment in FL; however, its evaluation may still have merit in DLBCL.

Background: Glofit is a novel, CD20xCD3 T-cell-engaging bispecific antibody that provides monovalent binding to CD3 on T cells and bivalent binding to CD20 on B cells. As monotherapy, Glofit has shown promising response rates with manageable safety in R/R B-cell non-Hodgkin lymphoma (B-NHL) patients (pts; [Carlo-Stella et al. EHA 2021]). Because of their distinct and complementary mechanism of action, there is a rationale for combining Glofit with the anti-CD79b-targeted antibody-drug conjugate, Pola. NP39488 (NCT03533283) is a Phase Ib/II, open-label, multicenter, dose-escalation (DE) and expansion study evaluating Glofit + Pola or atezolizumab in R/R B-NHL pts (Hutchings et al. ASH 2019). Here, we report preliminary safety and efficacy data for Glofit + Pola in pts with R/R DLBCL during DE and expansion at the recommended Phase II dose (RP2D). Methods: To mitigate the risk of cytokine release syndrome (CRS), a single 1000mg dose of obinutuzumab pre-treatment was administered on Cycle (C) 1 Day (D) 1 alongside step-up dosing (SUD) of Glofit on C1D8 and C1D15. Glofit was subsequently administered at the target dose from C2D1, every 3 weeks up to C12. Pola was administered at 1.8mg/kg on C1D2 and then on D1 of each subsequent cycle up to C6. The primary objective was to establish the RP2D of Glofit in combination with Pola. Results: As of June 10, 2021 (clinical cut-off date [CCOD]), 44 pts were treated with ≥1 cycle; median follow-up was 3.2 months (95% confidence interval: 1.4-3.5). In the first DE cohort, 7 pts had received Glofit at 2.5mg (C1D8)/10mg (C1D15)/10mg (C2D1 onwards) plus Pola. In the second DE cohort, 4 pts received the Glofit target dose of 30mg on C1D15 and this was established as the RP2D. During the expansion phase at RP2D, an additional 34 pts were treated with ≥1 cycle. Of 44 pts, 29 (66%) had histology of R/R DLBCL, 8 (18%) had R/R high-grade B-cell lymphoma (HGBCL; 2 HGBCL not otherwise specified; 5 double-hit DLBCL; 1 triple-hit DLBCL) and 7 (16%) had R/R transformed follicular lymphoma. Pts (61% male) had a median age of 65.5 years (range: 29-82) and received a median of two prior lines (range: 1−5). Twenty-eight (64%) pts were refractory to their last therapy; 2 pts had not been treated with Glofit at the CCOD. The most frequent adverse event (AE) was CRS (55%; 23/42 pts): Grade (Gr) 1 (n=18); Gr 2 (n=7); no Gr ≥3 CRS events were observed (Lee et al. 2019 ASTCT criteria). Of the 7 pts with Gr 2 CRS, 5 were treated with tocilizumab and fluids for hypotension, and 4 pts were treated with low-flow oxygen due to hypoxia. None of the pts required vasopressors or intensive care unit admission. Gr >3 AEs occurred in 52% (n=23) of pts; most commonly, neutropenia (27%) and anemia (23%). For neurological AEs (NAEs), 13 events were reported in 13 patients (29.5%, 13/44 pts), all were limited to Gr 1−2. The most common NAEs were headache and (11%, 5/44 pts) and insomnia (4.5%, 2/44 pts). No immune effector cell-associated neurotoxicity syndrome-like AEs were reported. Peripheral neuropathy due to Pola was reported in 5/44 pts (11%); all events were Gr 1. Serious AEs occurred in 22 pts (52%); none were CNS or neurological events. One pt experienced fatal COVID-19 pneumonia (not related). Study treatment was discontinued in 2 pts due to AEs (Gr 4 thrombocytopenia, and Gr 3 worsening of pre-existing renal impairment; both events were related to Glofit and Pola). At CCOD 33/44 pts were evaluable for interim (after 2 cycles, 1 target dose of Glofit) or primary (after 8 cycles) response; 6/33 pts had experienced progressive disease and discontinued study treatment. Overall response (OR) rate for both dosing cohorts was 73% (24/33) and complete response (CR) rate, per investigator was 51.5% (17/33). Of 7 pts treated with 2.5/10/10mg SUD Glofit, OR and CR rates were both 86% (6/7); durable responses at ≥6 months post-end of treatment were observed. Of 26 pts treated with 2.5/10/30 mg SUD Glofit, OR rate was 73% (19/26) and CR rate was 46% (12/26); 11.5% (3/26) pts had stable disease after 2 cycles of therapy. Duration of response and time on study by dosing cohort is shown in Figure. Biomarker and pharmacokinetic data will be provided. Conclusions: Glofit in combination with Pola showed tolerable safety and encouraging preliminary efficacy in R/R DLBCL pts. CRS and NAEs were limited to Gr 1 or 2, no new safety signals were detected for this combination, and the safety profile was consistent with that of the individual drugs. Updated data will be presented. Figure 1 Figure 1. Disclosures Hutchings: Genmab: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Celgene: Research Funding; Genentech: Honoraria, Research Funding; Incyte: Research Funding; Janssen: Honoraria, Research Funding; Novartis: Research Funding. Sureda: Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Research Funding, Speakers Bureau; BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bluebird: Membership on an entity's Board of Directors or advisory committees; Roche: Other: Support for attending meetings and/or travel; GSK: Consultancy, Honoraria, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Mundipharma: Consultancy; MSD: Consultancy, Honoraria, Speakers Bureau; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Terol: Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding; Roche: Consultancy; BMS: Consultancy; Hospital Clinico Valencia: Current Employment; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Travel. Bosch Albareda: Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria; Abbvie: Consultancy; AstraZeneca: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Kite: Honoraria; Sanofi: Honoraria; Lilly: Honoraria. Corradini: KiowaKirin; Incyte; Daiichi Sankyo; Janssen; F. Hoffman-La Roche; Kite; Servier: Consultancy; AbbVie, ADC Theraputics, Amgen, Celgene, Daiichi Sankyo, Gilead/Kite, GSK, Incyte, Janssen, KyowaKirin, Nerviano Medical Science, Novartis, Roche, Sanofi, Takeda: Honoraria; Amgen; Takeda; AbbVie: Consultancy, Honoraria, Other: Travel and accommodations; Novartis; Gilead; Celgene: Consultancy, Other: Travel and accommodations; BMS: Other: Travel and accommodation; Sanofi: Consultancy, Honoraria; Incyte: Consultancy; AbbVie, ADC Theraputics, Amgen, Celgene, Daiichi Sankyo, Gilead/Kite, GSK, Incyte, Janssen, KyowaKirin, Nerviano Medical Science, Novartis, Roche, Sanofi, Takeda: Consultancy; Novartis, Janssen, Celgene, BMS, Takeda, Gilead/Kite, Amgen, AbbVie: Other: travel and accomodations. Larsen: Novartis: Consultancy; Gilead: Consultancy; Odense University Hospital, Denmark: Current Employment; Celgene: Consultancy; BMS: Consultancy. Rueda Dominguez: Hospital Regional Universitario de Malaga: Current Employment; Roche: Consultancy; Takeda: Consultancy; Gilead: Consultancy; Merck Serono: Consultancy; BMS: Consultancy; MSD: Consultancy. Panchal: F. Hoffmann-La Roche Ltd: Current Employment. Bottos: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. Carlile: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company; AstraZeneca: Current equity holder in publicly-traded company, Ended employment in the past 24 months. Wang: F. Hoffmann-La Roche Ltd: Current Employment; Peking University Third Hospital, Beijing, China: Ended employment in the past 24 months. Filézac De L'Étang: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. Tandon: Roche Products Ltd: Current Employment, Current holder of individual stocks in a privately-held company. Sellam: Roche: Current Employment, Current equity holder in publicly-traded company. Gritti: Takeda: Consultancy; Roche: Consultancy; Kite Gilead: Consultancy; IQvia: Consultancy; Italfarmaco: Consultancy; Clinigen: Consultancy. 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. Polatuzumab vedotin (Polivy) is a CD79b-directed antibody-drug conjugate indicated in combination with bendamustine and a rituximab product for the treatment of adult pts with relapsed or refractory DLBCL, not otherwise specified, after at least two prior therapies.

Introduction: Diffuse large B-cell lymphoma (DLBCL) is a significant source of cancer morbidity and mortality. More than half of all newly diagnosed patients are older than 65 years, among whom the 5-year relative survival rate is 54% (SEER 2020). Prior research has shown that not all elderly patients (≥80 years old) receive R-CHOP or mini-R-CHOP regimens as the first line of therapy (LoT); those who do not may have suboptimal outcomes (Williams, et al. Cancer 2015; Hamlin, et al. Oncologist 2014; Juul, et al. Eur J Cancer 2018). This study leverages two real-world data (RWD) sources, Flatiron Health (FH) electronic health record-derived de-identified database and SEER-Medicare (SEER-M) to characterize elderly patients with DLBCL (including observed treatment patterns), summarize overall survival (OS) outcomes, and identify unmet medical needs in this population. Methods: RWD from FH included patients with a DLBCL diagnosis on or after January 1, 2011, with follow-up until May 31, 2020. The SEER-M database is a linkage of two population-based RWD sources: the SEER Cancer Registry and Medicare claims database. RWD from SEER-M for this study included patients with a DLBCL diagnosis between January 1, 2011 and December 31, 2015, with follow-up until December 31, 2016. All fee-for-service Medicare enrollees in SEER-M had to have complete claims. RWD for basic demographics, treatments and outcomes were analyzed from both datasets; FH's database included data on certain clinical characteristics including granularity for dosing data when available, in comparison to SEER-M. This descriptive analysis included patients who were aged ≥80 years at diagnosis. Among patients in the FH database who received R-CHOP as first LoT and had available dosing data, those who received Results: The study included 725 patients from the FH database and 2613 patients from the SEER-M database; patient characteristics and outcomes were generally consistent between the two datasets. In total, 16% and 35% of the elderly patients had no record of systemic treatment in FH and SEER-M respectively (Table). More than half of the treated patients received R-CHOP in the first LoT (63% and 53% in FH and SEER-M, respectively); other patients received attenuated regimens, including rituximab plus bendamustine (R-Benda), rituximab plus cyclophosphamide, vincristine and prednisolone (R-CVP), and rituximab (R) monotherapy. Patients who received R-CHOP in the first LoT had numerically longer median OS (Flatiron: 55.0 months [95% CI: 41.8-NA]; SEER-M: 50.7 months [95% CI: 45.9-62.9]) compared with those who received other regimens (Figure A, B). Untreated patients had a median survival of 3.1 months (95% CI: 2.3-5.2) in the Flatiron dataset and 2.0 months (95% CI: 1.8-2.2) in the SEER-M dataset. Among those who received R-CHOP and with available dosing data, 51% received reduced-dose R-CHOP in the first LoT and OS appeared shorter than for patients who received full-dose R-CHOP (Figure C). Conclusions: Despite differences between the databases, RWD in FH and SEER-M both demonstrate considerable variation in the regimens received by elderly DLBCL patients, with 16-35% receiving no treatment and >50% receiving attenuated regimens including reduced-dose R-CHOP. Patients receiving regimens other than R-CHOP had a numerically lower survival probability compared with the standard of care (SoC) R-CHOP/reduced-dose R-CHOP. These data show a high unmet medical need among elderly patients with DLBCL who may not be able to tolerate immunochemotherapy regimens that have been evaluated in trials for a carefully selected patient population. Further research will aim to assess prognostic factors at the time of treatment initiation, as well as gather information on comorbidities and other factors that may prevent elderly patients from receiving SoC R-CHOP; these patients may be candidates for better-tolerated novel approaches. Disclosures Shewade: Genentech, Inc.: Current Employment. Olszewski:TG Therapeutics: Research Funding; Adaptive Biotechnologies: Research Funding; Genentech, Inc.: Research Funding; Spectrum Pharmaceuticals: Research Funding. Pace:Genentech, Inc.: Current Employment; Exponent: Ended employment in the past 24 months; Prior employer was a consulting firm. No expert testimony given. No relevant consulting work done.: Consultancy. Surinach:Seattle Genetics: Research Funding. Sellam:F. Hoffmann-La Roche: Current Employment. Mueller:Genentech, Inc.: Current Employment, Ended employment in the past 24 months; F. Hoffmann-La Roche: Current equity holder in publicly-traded company. O'Hear:Genentech, Inc.: Current Employment; F. Hoffmann-La Roche: Current equity holder in publicly-traded company.

Introduction: Up to 30% of patients (pts) aged ≥75 years do not receive standard chemoimmunotherapy (CIT) as first-line (1L) treatment for diffuse large B-cell lymphoma (DLBCL) due to concerns about frailty and comorbidities. Poor outcomes are commonly reported for elderly/unfit pts with 1L DLBCL who receive no treatment, reduced-dose R-CHOP or other therapies such as R-CVP and R-bendamustine (Morrison, et al. J Geriatr Oncol 2020); less toxic, efficacious alternatives to full-dose CIT are needed. Mosunetuzumab (Mosun) is a full-length, fully humanized IgG1 CD20/CD3 bispecific antibody that redirects T cells to engage and eliminate malignant B cells. Single-agent Mosun has shown promising efficacy (including durable complete responses [CRs]) and tolerable safety in relapsed/refractory DLBCL pts in an ongoing Phase I study (GO29781; NCT02500407; Bartlett, et al. ASCO 2019, Schuster, et al. ASH 2019). Here we present early clinical data with Mosun as 1L therapy for elderly/unfit pts with DLBCL. Methods: GO40554 (NCT03677154) is a Phase I/II, open-label, multicenter study. We report data from Cohort B, designed to evaluate the safety, pharmacokinetics (PK) and preliminary efficacy of Mosun in pts with 1L DLBCL who are unable to tolerate full-dose CIT. Two safety evaluation cohorts were planned to receive Mosun at 13.5mg and 30mg, followed by an expansion phase. No safety concerns emerged following evaluation of the two safety cohorts. Eligible pts were aged ≥80 years or 60-79 years with impairment in ≥1 activity of daily living (ADL) or instrumental ADL, or with impairment in cardiac, renal or liver function precluding the use of full-dose CIT. After optional pre-phase treatment with prednisone with or without vincristine, pts received Mosun intravenously with step-up dosing on Day (D) 1, 8 and 15 of Cycle (C) 1, followed by a fixed dose on D1 of each subsequent 21-day cycle. Interim response assessment (IRA) occurred after C4 and primary response assessment (PRA) occurred after C8, with an option to continue up to maximum 17 cycles in case of partial remission (PR) following PRA. Results: As of May 27, 2020, 19 pts in Cohort B had received Mosun (1mg [C1 D1]/2mg [C1 D8]/13.5mg [C1 D15 onwards], n=8; 1/2/30mg, n=11). Eight pts were enrolled in the 13.5mg safety evaluation cohort and 11 enrolled in the 30mg safety cohort and expansion (7+4 respectively). Median age was 84 (range: 67-100) years, 14 (74%) pts were women, 10 (53%) had Ann Arbor stage III-IV and 17 (90%) had an IPI score ≥2. Median Mosun cycles received was 6 (range: 2-9; one pt in PR continued treatment). Among 19 pts, 16 (84%) had ≥1 adverse event (AE), 13 (68%) had ≥1 AE related to Mosun and 7 (37%) experienced a Grade (Gr) 3-4 AE, of which 4 were related to Mosun. No fatal AEs were observed. The most common (>10%) treatment-emergent AEs were cytokine release syndrome (CRS; n=9, 47%), rash (n=4, 21%), neutropenia, nausea, decreased appetite, dry mouth, fatigue, pain and muscle spasms (all n=2, 11%). All CRS events were Gr 1 by ASTCT consensus criteria (Lee, et al. Biol Blood Marrow Transplant 2019); no pts experienced hypotension, hypoxia or required tocilizumab or steroid treatment. No severe (Gr ≥3) neurologic AEs were observed. Gr 2 (ICAN) neurotoxicity was observed in one (5%) pt on C1D2 with symptoms of inability to answer questions, drowsiness, weakness and somnolence, combined with Gr 1 CRS (fever and tachycardia). The event resolved after 2 days and was considered related to Mosun. Eight (42%) pts discontinued Mosun early due to progressive disease (PD) between C2-C6. No pts discontinued Mosun due to an AE. Among all treated pts, the overall response rate was 58% (11/19) and CR rate was 42% (8/19). At Mosun dose 13.5mg, 3/8 pts (38%) achieved a CR, 2 (25%) had a PR and 3 (38%) had PD at the PRA. At Mosun dose 30mg, response was available at IRA: 5/11 pts (45.5%) achieved a CR, 1 (9%) had a PR and 5 (45.5%) had PD. Of the 8 pts with PD (from both dosing cohorts), 5 have received salvage therapy post progression. Figure 1 shows a durable response of almost a year for the first responder. Correlative studies of T-cell response by flow cytometry and cytokine expression, and PK analyses are ongoing and will be provided. Conclusions: Early clinical data indicate that single-agent Mosun confers notable efficacy and remarkable tolerability for previously untreated elderly/unfit DLBCL pts. Mosun is a promising chemotherapy-free regimen for patients who otherwise have limited options. Disclosures Olszewski: Spectrum Pharmaceuticals: Research Funding; TG Therapeutics: Research Funding; Adaptive Biotechnologies: Research Funding; Genentech, Inc.: Research Funding. Avigdor:Takeda, Gilead, Pfizer: Consultancy, Honoraria; Janssen, BMS: Research Funding. Babu:Amgen: Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Fort Wayne Medical Oncology & Hematology: Current Employment, Current equity holder in publicly-traded company; Lilly: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Sanofi: Research Funding; Janssen Oncology: Research Funding; Lutheran Hospital: Other; Bayer: Honoraria; AstraZeneca: Consultancy, Honoraria; AstraZeneca/MedImmune: Research Funding; Boehringer Ingelheim: Consultancy; Alexion Pharmaceuticals: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding, Speakers Bureau; Argenx: Consultancy, Research Funding; Novartis: Research Funding; Genentech, Inc./ F. Hoffmann-La Roche: Research Funding; Syndax: Research Funding; Nektar: Research Funding; Merck: Research Funding; AbbVie: Research Funding; TG Therapeutics: Research Funding. Levi:Abbvie Inc: Consultancy, Research Funding. Abadi:Abbvie Inc: Research Funding; Roche, Gilead, Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Holmes:Texas Oncology PA: Current Employment; Gilead/Kite, Celgene/Juno, Rigel, Karyopharm, Janssen, Dova: Consultancy; Gilead/Kite, Novartis, Autolus, Celgene/Juno/bluebird, Genentech, Inc., Rigel, Janssen, Unum, ADC Therapeutics, Seattle Genetics, Incyte, Verastem: Research Funding; Kite, Karyopharm, Seattle Genetics, Rigel, Dova: Speakers Bureau. McKinney:UNUM, Molecular Templates, Incyte, Beigene, Denovo Biopharma, Pharmacyclics, Nordic Nanovector, BMS, Genentech, Inc., Celgene: Research Funding; Kite/Gilead: Honoraria, Speakers Bureau; Kite/Gilead, Seattle Genetics, Molecular Templates, BTG, Pharmacyclics, Verastem, Genentech, Inc., Celgene: Consultancy. McCord:F. Hoffmann-La Roche: Current equity holder in publicly-traded company; Genentech, Inc.: Current Employment. Xie:F. Hoffmann-La Roche: Current Employment. Chen:Janssen Pharmaceuticals: Current equity holder in publicly-traded company; Bristol-Myer Squibb: Current equity holder in publicly-traded company, Ended employment in the past 24 months; Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company. Sarouei:Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company. Qayum:F. Hoffmann-La Roche: Current Employment. O'Hear:Genentech, Inc.: Current Employment; F. Hoffmann-La Roche: Current equity holder in publicly-traded company. Sellam:F. Hoffmann-La Roche: Current Employment. Eradat:UCLA Medical Center, David Geffen school of Medicine at UCLA: Current Employment; Genentech, Inc.: Consultancy, Honoraria, Research Funding, Speakers Bureau; F. Hoffmann-La Roche: Consultancy, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding, Speakers Bureau; Astrazeneca, Atara, Kite, Juno, Acerta, BeiGene, Celgene: Research Funding. OffLabel Disclosure: Mosunetuzumab (RG7828; CD20-TDB) is a full-length, fully humanized immunoglobulin G1 (IgG1) bispecific antibody targeting both CD3 (on the surface of T cells) and CD20 (on the surface of B cells). Mosunetuzumab redirects T cells to engage and eliminate malignant B cells. Mosunetuzumab is an investigational agent.

GOYA was a randomized phase 3 study comparing obinutuzumab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) vs standard-of-care rituximab plus CHOP in patients with previously untreated diffuse large B-cell lymphoma (DLBCL). This retrospective analysis of GOYA aimed to assess the association between progression-free survival (PFS) and overall survival (OS) with positron emission tomography (PET)–based complete response (CR) status. Overall, 1418 patients were randomly assigned to receive 8 21-day cycles of obinutuzumab (n = 706) or rituximab (n = 712) plus 6 or 8 cycles of CHOP. Patients received a mandatory fluoro-2-deoxy-d-glucose–PET/computed tomography scan at baseline and end of treatment. After a median follow-up of 29 months, the numbers of independent review committee–assessed PFS and OS events in the entire cohort were 416 (29.3%) and 252 (17.8%), respectively. End-of-treatment PET CR was highly prognostic for PFS and OS according to Lugano 2014 criteria (PFS: hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.19-0.38; P < .0001; OS: HR, 0.12; 95% CI, 0.08-0.17; P < .0001), irrespective of international prognostic index score and cell of origin. In conclusion, the results from this prospectively acquired large cohort corroborated previously published data from smaller sample sizes showing that end-of-treatment PET CR is an independent predictor of PFS and OS and a promising prognostic marker in DLBCL. Long-term survival analysis confirmed the robustness of these data over time. Additional meta-analyses including other prospective studies are necessary to support the substitution of PET CR for PFS as an effective and practical surrogate end point. This trial was registered at www.clinicaltrials.gov as #NCT01287741.

Context Mosun, a full-length, humanized, IgG1 CD20×CD3 bispecific antibody, demonstrated efficacy/safety in relapsed/refractory DLBCL (NCT02500407; Schuster, et al. ASH 2019). The phase I/II multicenter GO40554 (NCT03677154) study showed similar results for elderly/unfit patients with first-line DLBCL intolerant of full-dose chemoimmunotherapy (CIT) (Olszewski, et al. ASH 2020). Objective To describe updated GO40554 study data. Methods Two safety-evaluation cohorts were assessed (Mosun 13.5 mg and 30 mg), then a 30 mg expansion phase. Patients were aged ≥80 years; 60–79 years with impairment in ≥1 activity of daily living (ADL); instrumental ADL; or impaired cardiac, renal, or liver function. Patients received optional pre-treatment with prednisone (+/– vincristine), then intravenous mosun in step-up doses on days (D)1 (1 mg), 8 (2 mg), and 15 (full-dose: 13.5/30 mg) of cycle (C)1, and full (C1D15) dose on D1 of each 21-day cycle for eight cycles, continuing for ≤17 cycles. Results As of January 15, 2021, 40 patients received mosun (13.5 mg safety cohort, n=8; 30 mg safety cohort, n=7; 30 mg expansion, n=25). Median age: 84 (range 67–100) years; 50% with Ann Arbor Stage III–IV, 80% with IPI score ≥2. Of 40 treated patients, 27 (67.5%) had ≥1 mosun-related adverse event (AE); 15 (37.5%) had a grade 3–4 AE. Most common treatment-emergent AE: cytokine release syndrome (CRS; n=9, 22.5%); five patients had neutropenia (12.5%). Six (15%) patients had grade 1 CRS per ASTCT (Lee, et al. Biol Blood Marrow Transplant 2019); three (7.5%) had grade 2 CRS, all managed with supportive care, fluids for hypotension, steroids, or low-flow oxygen, as required (no tocilizumab, vasopressors, high-flow oxygen, or intensive care). 14 (35%) patients discontinued due to progressive disease (PD). Overall response rate for efficacy-evaluable patients (n=31): 67.7%; complete response (CR) rate: 41.9%. Responses with 13.5 mg mosun: CR: 37.5%; PR: 37.5%; PD: 25%; with 30 mg mosun: CR: 43.5%; PR: 21.7%; stable disease/PD: 34.8%. Four durable responses were observed ≥12 months from start of therapy in 13 patients with CR (11 ongoing). Conclusions Mosun showed promising efficacy, including durable responses, and tolerable safety for elderly/unfit patients with 1L DLBCL; it should be further evaluated as a chemotherapy-free backbone for patients unable to tolerate standard CIT.

Risk of hepatitis B virus (HBV) reactivation was assessed in B-cell non-Hodgkin lymphoma (NHL) patients with resolved HBV infection (hepatitis B surface antigen negative, hepatitis B core antibody positive) who received obinutuzumab- or rituximab-containing immunochemotherapy in the phase 3 GOYA and GALLIUM studies. HBV DNA monitoring was undertaken monthly to 1 year after the last dose of study drug. In case of HBV reactivation (confirmed, HBV DNA ≥29 IU/mL), immunochemotherapy was withheld and nucleos(t)ide analog treatment (preemptive NAT) started. Immunochemotherapy was restarted if HBV DNA became undetectable or reactivation was not confirmed, and discontinued if HBV DNA exceeded 100 IU/mL on NAT. Prophylactic NAT was allowed by investigator discretion. Among 326 patients with resolved HBV infection, 27 (8.2%) had HBV reactivation, occurring a median of 125 days (interquartile range, 85-331 days) after the first dose. In 232 patients without prophylactic NAT, 25 (10.8%) had HBV reactivation; all received preemptive NAT. Ninety-four patients received prophylactic NAT; 2 (2.1%) had HBV reactivation. No patients developed HBV-related hepatitis. On multivariate Cox analysis, detectable HBV DNA at baseline was strongly associated with an increased risk of reactivation (adjusted hazard ratio [HR], 18.22; 95% confidence interval [CI], 6.04-54.93; P < .0001). Prophylactic NAT was strongly associated with a reduced risk (adjusted HR, 0.09; 95% CI, 0.02-0.41; P = .0018). HBV DNA monitoring–guided preemptive NAT was effective in preventing HBV-related hepatitis during anti–CD20-containing immunochemotherapy in B-cell NHL patients with resolved HBV infection. Antiviral prophylaxis was also effective and may be appropriate for high-risk patients. These trials were registered at www.clinicaltrials.gov as NCT01287741 (GOYA) and NCT01332968 (GALLIUM).

Background Rituximab (R) plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) is the current standard therapy for diffuse large B cell lymphoma (DLBCL). Obinutuzumab (G), a glycoengineered, type II anti-CD20 monoclonal antibody, has shown activity and an acceptable safety profile when combined with CHOP (G-CHOP) in patients with advanced DLBCL. We present the final analysis results of the Phase III GOYA study (NCT01287741), which compared the efficacy and safety of G-CHOP versus R-CHOP in patients with previously untreated DLBCL. Methods Patients aged ≥ 18 years with previously untreated advanced DLBCL were randomly assigned to receive eight 21-day cycles of R or G, plus six or eight cycles of CHOP. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival, other time-to-event endpoints, and safety; investigator-assessed PFS by cell of origin subgroup was an exploratory endpoint. Results A total of 1418 patients were randomized, with 1414 included in this final analysis (G-CHOP, N = 704; R-CHOP, N = 710). Five-year PFS rates were 63.8% and 62.6% for G-CHOP and R-CHOP, respectively (stratified hazard ratio 0.94, 95% CI 0.78–1.12; p = 0.48). The results of the secondary efficacy endpoints did not show a benefit of G-CHOP over R-CHOP. In the exploratory analysis, a trend towards benefit with G-CHOP over R-CHOP was apparent in the patients with germinal center B cell DLBCL. The safety profile of G-CHOP was as expected, and no new safety signals were observed. More grade 3–5 (75.1% vs 65.8%), serious (44.4% vs 38.4%), and fatal (6.1% vs 4.4%) adverse events (AEs) were observed in the G-CHOP arm compared with the R-CHOP arm, respectively, with the most common fatal AEs being infections. A higher incidence of late-onset neutropenia occurred in the G-CHOP arm (8.7%) versus the R-CHOP arm (4.9%). Conclusions The final analysis, similar to the primary analysis, did not show a PFS benefit of G-CHOP over R-CHOP in previously untreated patients with DLBCL. The results of the secondary endpoints were consistent with the primary endpoint. Further exploratory analyses and investigation of biomarkers are ongoing.

Central nervous system (CNS) relapse carries a poor prognosis in diffuse large B-cell lymphoma (DLBCL). Integrating biomarkers into the CNS–International Prognostic Index (CNS-IPI) risk model may improve identification of patients at high risk for developing secondary CNS disease. CNS relapse was analyzed in 1418 DLBCL patients treated with obinutuzumab or rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone chemotherapy in the phase 3 GOYA study. Cell of origin (COO) was assessed using gene-expression profiling. BCL2 and MYC protein expression was analyzed by immunohistochemistry. The impact of CNS-IPI, COO, and BCL2/MYC dual-expression status on CNS relapse was assessed using a multivariate Cox regression model (data available in n = 1418, n = 933, and n = 688, respectively). High CNS-IPI score (hazard ratio [HR], 4.0; 95% confidence interval [CI], 1.3-12.3; P = .02) and activated B-cell‒like (ABC) (HR, 5.2; 95% CI, 2.1-12.9; P = .0004) or unclassified COO subtypes (HR, 4.2; 95% CI, 1.5-11.7; P = .006) were independently associated with CNS relapse. BCL2/MYC dual-expression status did not impact CNS relapse risk. Three risk subgroups were identified based on the presence of high CNS-IPI score and/or ABC/unclassified COO (CNS-IPI-C model): low risk (no risk factors, n = 450 [48.2%]), intermediate risk (1 factor, n = 408 [43.7%]), and high risk (both factors, n = 75 [8.0%]). Two-year CNS relapse rates were 0.5%, 4.4%, and 15.2% in the respective risk subgroups. Combining high CNS-IPI and ABC/unclassified COO improved CNS relapse prediction and identified a patient subgroup at high risk for developing CNS relapse. The study was registered at www.clinicaltrials.gov as #{"type":"clinical-trial","attrs":{"text":"NCT01287741","term_id":"NCT01287741"}}NCT01287741.

Introduction: Multiple response criteria have been proposed for the assessment of treatment response in lymphoma patients (pts). The Lugano 2014 criteria have been adopted as the current standard for response assessment in lymphoma (Cheson et al. J Clin Oncol 2014), incorporating 18F fludeoxyglucose (FDG)-positron emission tomography (PET)-computed tomography (CT) into standard staging of FDG-avid lymphomas. For non-FDG avid lymphomas, and when PET is not available, Lugano criteria use bi-dimensional tumor measurements of up to six CT target lesions. The more recently proposed Response Evaluation Criteria in Lymphoma (RECIL) (Younes et al. Annals Oncol 2017) were developed based on the hypothesis that uni-dimensional measurements of up to three target lesions could be used to assess response at a similar level of accuracy to the Lugano criteria. The prognostic value of Lugano 2014 versus RECIL 2017 criteria has not yet been assessed in large clinical trials. We compared the prognostic performance of Lugano and RECIL criteria in pts from the Phase III GOYA study (NCT01287741), which compared the efficacy of obinutuzumab (GA101, G) and rituximab (R) in combination with CHOP (G-CHOP vs R-CHOP) in previously untreated pts with CD20-positive DLBCL. Methods: In the GOYA study, pts were randomized 1:1 to receive either G-CHOP or R-CHOP (stratification factors: number of planned chemotherapy cycles, International Prognostic Index [IPI], and geographic region). FDG-PET scans were mandatory at sites where a PET scanner was available and were performed at screening and 6-8 weeks after the last study treatment. Response was assessed prospectively based on Cheson 2007 criteria and retrospectively according to standard Lugano 2014 criteria. A retrospective analysis based on RECIL 2017 criteria was also performed. Response categories by RECIL criteria were cross-tabulated against those by Lugano criteria. Estimates of the treatment effect were expressed as hazard ratios (HRs) with 95% confidence intervals (CIs) using stratified log-rank tests. The impact of covariates on PFS and OS were analyzed using a multivariate Cox model. Landmark analyses of PFS and OS according to end of treatment (EoT) complete response (CR)/non-CR status were performed, and the prognostic value of response at EoT was compared for the two methods. Results: Of the 1418 pts (intention-to-treat [ITT] population) in the GOYA study, 1334 had PET data and were evaluable for this analysis. Good agreement between Lugano and RECIL criteria was observed for EoT CR status, with 894/966 (92.5%) pts with a complete metabolic response (CMR) by Lugano classified as CR by RECIL (Table). However, 40/63 (63.5%) pts with progressive metabolic disease (PMD) at EoT according to Lugano criteria had a partial response (PR) or minor response (MR) by RECIL criteria, showing poor agreement for these variables. Of the 43 pts with PMD by Lugano and non-PD by RECIL at EoT, 15 pts had no PFS event by Lugano as assessed by CT and could be considered false positives. Concordance for PFS by CT was high between the two criteria, with a kappa estimate of 0.77 (95% CI: 0.74, 0.80). EoT CR status by RECIL was highly prognostic for PFS (stratified HR, 0.32; 95% CI: 0.25, 0.43; p Conclusions: EoT CR status according to RECIL 2017 criteria showed a high concordance with CMR status by Lugano 2014 criteria and was highly prognostic for PFS and OS in previously untreated DLBCL; however, discordance was seen for the identification of PD by RECIL compared with Lugano criteria. PFS as assessed by CT by RECIL, based on uni-dimensional size measurements of up to three target lesions, showed high concordance with PFS by Lugano criteria, based on bi-dimensional size measurements of up to six target lesions. Table Disclosures Kostakoglu: F. Hoffman-La Roche: Consultancy; Genentech: Consultancy. Martelli:F. Hoffman-La Roche, Celgene, Janssen, Sandoz, Novartis, Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Honoraria; Servier: Honoraria; F. Hoffman-La Roche, Celgene, Janssen, Sandoz, Novartis, Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees. Sehn:Astra Zeneca: Consultancy, Honoraria; Acerta: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; F. Hoffmann-La Roche/Genentech: Consultancy, Honoraria, Research Funding; TG Therapeutics: Consultancy, Honoraria; Janssen-Ortho: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria; Verastem: Consultancy, Honoraria; Janssen-Ortho: Honoraria; Lundbeck: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria; Acerta: Consultancy, Honoraria; F. Hoffmann-La Roche/Genentech: Consultancy, Honoraria, Research Funding; TEVA Pharmaceuticals Industries: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; TEVA Pharmaceuticals Industries: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Apobiologix: Consultancy, Honoraria. Trněný:Amgen: Consultancy, Honoraria; Gilead Sciences: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; MorphoSys: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; F. Hoffmann-La Roche: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Celgene: Consultancy. Vitolo:Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; F. Hoffmann-La Roche: Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Juno Therapeutics: 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; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kite: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Knapp:F. Hoffmann-La Roche Ltd: Employment. Mattiello:F. Hoffmann-La Roche Ltd: Employment. Nielsen:F. Hoffmann-La Roche Ltd: Employment, Equity Ownership. Sahin:F. Hoffmann-La Roche Ltd: Employment, Equity Ownership. Sellam:Roche: Employment, Equity Ownership. Ward:Hoffmann La Roche: Employment, Equity Ownership. Younes:Roche: Consultancy, Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Curis: Honoraria, Research Funding; Merck: Honoraria, Research Funding; Abbvie: Honoraria; Takeda: Honoraria; Pharmacyclics: Research Funding; AstraZeneca: Research Funding; Genentech: Research Funding; Biopath: Consultancy; Xynomics: Consultancy; Epizyme: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; HCM: Consultancy; BMS: Research Funding; Syndax: Research Funding. OffLabel Disclosure: GAZYVA (obinutuzumab) is a CD20-directed cytolytic antibody and is indicated for the following: in combination with chlorambucil, for the treatment of patients with previously untreated CLL; in combination with bendamustine followed by GAZYVA monotherapy, for the treatment of patients with FL who relapsed after, or are refractory to, a rituximab-containing regimen; in combination with chemotherapy followed by GAZYVA monotherapy in patients achieving at least a partial remission, for the treatment of adult patients with previously untreated stage II bulky, III or IV FL.

Introduction: The standard first line treatment for diffuse large B-cell lymphoma (DLBCL) is rituximab (R) plus CHOP (R-CHOP). However, approximately 35-40% of patients (pts) relapse following such treatment, and outcomes with salvage therapy remain poor. Obinutuzumab (GA101; G) is a fully humanized, glycoengineered, type II anti-CD20 monoclonal antibody. It has demonstrated greater direct cell death induction and antibody-dependent cellular cytotoxicity/phagocytosis activity than R, and has shown activity and an acceptable safety profile when combined with CHOP (G-CHOP) in first-line treatment of pts with advanced DLBCL (Sharman et al. Leuk Lymphoma 2019). GOYA (NCT01287741) was a randomized, open-label, multicenter Phase III study that compared the efficacy and safety of G-CHOP with R-CHOP in pts with previously untreated DLBCL. In the primary analysis (median observation period: 29 months), G-CHOP did not significantly improve investigator (INV)-assessed progression-free survival (PFS) compared with R-CHOP (Vitolo et al. J Clin Oncol 2017). Here, we present results from the final analysis of GOYA. Methods: Pts were aged ≥18 years, had histologically documented, previously untreated, CD20-positive DLBCL, with adequate hematologic function, ≥1 bi-dimensionally measurable lesion, an ECOG performance status of ≤2, and were classified as being in an International Prognostic Index (IPI) risk group of high, high-intermediate, or low-intermediate risk. Low-risk pts with an IPI score of 1 (not due to age alone) or 0 with bulky disease (1 lesion ≥7.5cm) were also eligible. Pts were randomized (1:1) to 8 (21-day) cycles of G (1000mg i.v. on Days [D]1, 8 and 15, Cycle [C]1 and D1, C2-8) or R (375mg/m2 i.v. on D1, C1-8) in combination with 6 or 8 cycles of CHOP. Preplanned radiotherapy was allowed for bulky or extranodal disease. The primary endpoint was INV-assessed PFS. Secondary endpoints included independent review committee-assessed PFS (primary analysis only); overall survival (OS); complete response (CR) and overall response rate (ORR) with or without PET (according to modified Cheson 2007 criteria); event-free survival; disease-free survival; duration of response; time to next anti-lymphoma treatment; PFS according to cell of origin (COO; germinal center B cell [GCB] or activated B cell [ABC]), as an exploratory endpoint; and safety. Results: In total, 1418 pts were randomized in GOYA; of these, 704 pts who received G-CHOP and 710 who received R-CHOP were included in this final analysis (clinical cut-off date: January 31, 2018). Overall median follow-up was 47.7 months. Baseline characteristics were well balanced between the G-CHOP and R-CHOP arms. INV-assessed PFS was similar between G-CHOP and R-CHOP (5-year PFS, 63.8% vs 62.6%; stratified HR, 0.94; 95% CI: 0.78, 1.12; p=0.48; Table). There was no significant difference in 5-year OS between the G-CHOP and R-CHOP groups (77.0% vs 77.7%) or in CR or ORR (Table). In the subgroup analysis of pts with ABC, GCB and unclassified DLBCL, no significant reductions in risk of disease progression were observed (stratified HR for INV-PFS, 0.91 [95% CI: 0.61, 1.36], 0.80 [95% CI: 0.58, 1.12] and 1.10 [95% CI: 0.65, 1.88], respectively). No new safety signals were identified. Grade ≥3 adverse events (AEs; 75% vs 66%) and serious AEs (44% vs 38%) were more common with G-CHOP than R-CHOP. Grade ≥3 AEs of particular interest (≥2% of pts in either treatment arm) were more frequent in the G-CHOP arm: infusion-related reactions (10% vs 3%), neutropenia (57% vs 47%), infections (20% vs 16%), cardiac events (5% vs 3%), thrombocytopenia (6% vs 2%), and hemorrhagic events (3% vs 1%); secondary malignancies occurred in 3% and 2% of the R-CHOP and G-CHOP arms, respectively. AEs resulting in treatment withdrawal (12% [87/702] G-CHOP; 8% [58/701] R-CHOP) and AEs with fatal outcome (6% [43/702] G-CHOP; 4% [31/701] R-CHOP) were slightly more common with G-CHOP. The most common grade 5 AEs were pneumonia (n=5 both arms) and sepsis/septic shock (G-CHOP, n=7; R-CHOP, n=3). Conclusions: Consistent with the primary analysis, G-CHOP did not significantly improve INV-assessed PFS compared with R-CHOP in previously untreated pts with DLBCL. Furthermore, there was no significant difference in 5-year OS between the treatment arms. No unexpected safety signals were identified. Further investigation of outcomes is ongoing, including the prognostic value of COO and BCL2 positivity. Disclosures Sehn: F. Hoffmann-La Roche/Genentech: Consultancy, Honoraria, Research Funding; Lundbeck: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Acerta: Consultancy, Honoraria; Acerta: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria; F. Hoffmann-La Roche/Genentech: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Apobiologix: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; TEVA Pharmaceuticals Industries: Consultancy, Honoraria; Verastem: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria; Janssen-Ortho: Consultancy, Honoraria; Janssen-Ortho: Honoraria; Kite Pharma: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria; TEVA Pharmaceuticals Industries: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria. Martelli:F. Hoffman-La Roche, Celgene, Janssen, Sandoz, Novartis, Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Honoraria; F. Hoffman-La Roche, Celgene, Janssen, Sandoz, Novartis, Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Honoraria. Trněný:Gilead Sciences: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; MorphoSys: Consultancy, Honoraria; Celgene: Consultancy; Incyte: Consultancy, Honoraria; F. Hoffmann-La Roche: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Liu:Roche Pharma Development, Shanghai, China: Employment. Bolen:Genentech, Inc.: Employment; F. Hoffmann-La Roche: Equity Ownership. Knapp:F. Hoffmann-La Roche Ltd: Employment. Sahin:F. Hoffmann-La Roche Ltd: Employment, Equity Ownership. Sellam:Roche: Employment, Equity Ownership. Vitolo:Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: 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, Speakers Bureau; Kite: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. OffLabel Disclosure: GAZYVA (obinutuzumab) is a CD20-directed cytolytic antibody and is indicated for the following: in combination with chlorambucil, for the treatment of patients with previously untreated CLL; in combination with bendamustine followed by GAZYVA monotherapy, for the treatment of patients with FL who relapsed after, or are refractory to, a rituximab-containing regimen; in combination with chemotherapy followed by GAZYVA monotherapy in patients achieving at least a partial remission, for the treatment of adult patients with previously untreated stage II bulky, III or IV FL.

To compare the influence of three different nonpharmacological interventions on cortical activation, heart rate and peripheral oxygen saturation (SaO2 ) after heelstick in preterm infants.Twenty five preterm infants between 24 0/7 and 32 0/7 weeks of gestational age were randomized to either oral sucrose (S), facilitated tucking (FT) or a combination of the two interventions (SFT) prior to five heelsticks each within the first 14 days of life. SaO2 , heart rate and oxygenation of the somatosensory cortex, measured by near infrared spectroscopy (NIRS), were analysed.Hundred and twenty five heelsticks were performed. The heart rate increased significantly after heelstick in all three intervention groups (p 0.004 in all groups). The increase was higher in the FT group compared with the other groups (S: p = 0.007; SFT: p = 0.004). There was no difference among the two groups receiving sucrose (S and SFT; p = 0.87). SaO2 did not change significantly after heelstick in all intervention groups. Near infrared spectroscopy measurements did not show a significant change in the curve but patients in the FT group showed a trend towards higher average oxygenation of the contralateral somatosensory cortex.Oral sucrose seems to be more effective in reducing reaction to pain than FT. Application of both interventions did not show an additive effect.

Background: Evidence indicates that medical and demographic contextual factors (cFs) impact pain responses in preterm neonates, but the existing evidence is very heterogeneous. Aim: To explore the effect of cFs on pain responses to heel-stick procedures of preterm infants. Methods: This study was a secondary analysis of data collected during a randomized controlled trial examining pain response to nonpharmacological interventions across repeated heel sticks. Five heel sticks across the first 14 days of life were videotaped. Pain response was rated with the Bernese Pain Scale for Neonates (BPSN) by four raters blinded to the heel-stick phases (baseline, heel stick, recovery). Demographic and medical cFs were extracted from medical charts. Mixed single and multiple regression analyses were performed controlling for the intervention group, site and heel-stick phase. Results: Apgar scores at 1 min were negatively associated with behavioural (p = 0.002) BPSN scores, while Apgar scores at 5 min after birth were positively associated with behavioural (p = 0.006) scores. Accumulated number of painful procedures (p = 0.002) and gender (p = 0.02) were positively associated with physiological scores while continuous positive airway pressure CPAP (p = 0.009) and mechanical ventilation (p = 0.005) were negatively associated. Conclusion: Higher exposure to painful procedures, male infants and having CPAP or mechanical ventilation were cFs associated with physiological response. The only variables significantly associated with behavioural BPSN scores were Apgar scores but these relationships were inconsistent.

OBJECTIVES: To test the comparative effectiveness of 2 nonpharmacologic pain-relieving interventions administered alone or in combination across time for repeated heel sticks in preterm infants. METHODS: A multicenter randomized controlled trial in 3 NICUs in Switzerland compared the effectiveness of oral sucrose, facilitated tucking (FT), and a combination of both interventions in preterm infants between 24 and 32 weeks of gestation. Data were collected during the first 14 days of their NICU stay. Three phases (baseline, heel stick, recovery) of 5 heel stick procedures were videotaped for each infant. Four independent experienced nurses blinded to the heel stick phase rated 1055 video sequences presented in random order by using the Bernese Pain Scale for Neonates, a validated pain tool. RESULTS: Seventy-one infants were included in the study. Interrater reliability was high for the total Bernese Pain Scale for Neonates score (Cronbach’s α: 0.90–0.95). FT alone was significantly less effective in relieving repeated procedural pain (P < .002) than sucrose (0.2 mL/kg). FT in combination with sucrose seemed to have added value in the recovery phase with lower pain scores (P = .003) compared with both the single-treatment groups. There were no significant differences in pain responses across gestational ages. CONCLUSIONS: Sucrose with and without FT had pain-relieving effects even in preterm infants of

Introduction: Rituximab (R) plus CHOP (R-CHOP) is standard of care for patients (pts) with previously untreated DLBCL. Although most pts have long-term responses, up to 40% of pts fail to achieve a remission or relapse. Atezolizumab (atezo) is a fully humanized anti-programmed death-ligand 1 (PD-L1) antibody with a complementary mechanism of action to R. An ongoing Phase I/II study (NCT02596971) is evaluating the safety and efficacy of atezo in combination with R-CHOP (R-CHOP-atezo) in DLBCL pts. Results from the primary analysis are reported. Methods: This open-label, multicenter study enrolled pts (≥18 years; ECOG PS 0-2) with previously untreated advanced DLBCL (Ann Arbor Stage III/IV, International Prognostic Index [IPI] score ≥2 or Stage II with bulky disease [at least 1 lesion ≥7cm]). Pts received induction treatment with R-CHOP-atezo (8 cycles [each 21 days] of R [375mg/m2 IV on Day 1 (Cycles 1-8)] and atezo [1200mg IV on Day 1 (Cycles 2−8)], and 6 or 8 cycles of CHOP [as determined by the investigator (INV)]). Pts who achieved a complete response (CR) at end of induction (EOI) received consolidation treatment with atezo 1200mg IV on Day 1 of Cycles 9─25, every 21 days for 12 months (mo). Primary endpoints were safety, and efficacy as determined by CR rate at EOI by independent review committee (IRC) using modified Lugano 2014 criteria (if bone marrow [BM] involvement at baseline [BL], CR was confirmed with a negative BM biopsy at EOI; designation of partial response [PR] on PET required that CR or PR on CT scan were met). Secondary endpoints included CR at EOI assessed by INV (modified Lugano 2014 criteria) and by IRC and INV (Cheson et al. J Clin Oncol 2007). Minimal residual disease (MRD) was evaluated at EOI using the Adaptive ImmunoSEQ® NGS platform (v2). Results: At the data cut-off (April 11, 2018), 42 pts were enrolled and received treatment (safety population); 7 pts discontinued during the induction phase (1 protocol violation, 1 withdrawal of consent [these 2 pts discontinued after Cycle 1, Day 1 and were not treated with atezo, and were not included in the efficacy analysis], 4 adverse events [AEs], 1 progressive disease [PD]). Of 35 pts completing induction, 30 entered the consolidation phase; 5 pts discontinued at EOI (2 PD, 3 PR). Pt demographics and disease characteristics are shown in Table 1. Among 40 pts evaluable for response (efficacy population), 31 pts (77.5%) had a CR and 4 pts (10%) had a PR by IRC (modified Lugano 2014 criteria); PD occurred in 2 pts (5%), and 3 pts (7.5%) were not evaluable. Response assessments by Cheson et al. (J Clin Oncol 2007) were similar by IRC and INV; IRC assessment showed 31 (77.5%) CRs, 5 (12.5%) PRs, 2 (5%) pts with PD and 1 with SD (Table 2). MRD was evaluable in 26 pts at BL: 10 pts were MRD negative and 16 pts were MRD positive. Of the 16 MRD positive pts at BL, MRD data were available for 14 at EOI: 13 pts were negative and 1 pt was positive (PR by INV and IRC). Median dose intensity was >99% for the induction phase (median exposure 6.7 mo [range 1.5-7.3]) and 100% for the consolidation phase (median exposure 3.7 mo [range 0.7-9.3]). During induction, all 42 pts (100%) had ≥1 AE, 29 (69%) had a grade (Gr) 3-4 AE and 12 (29%) had a serious AE. No fatal AEs were reported. AEs led to any treatment discontinuation in 6 pts (14%) (Gr 3 neutropenia and Gr 3 transaminase increase, Gr 2 hyperthyroidism, Gr 3 lipase increase, Gr 1-2 peripheral neuropathy, Gr 4 thrombocytopenia), dose reduction (CHOP) in 9 pts (21%) (Gr 4 anemia, Gr 3 pancytopenia, Gr 2 paresthesia, Gr 4 neutropenia and Gr 1-2 peripheral neuropathy) and dose interruption (missed doses and dose delays) in 15 pts (36%). Five pts had AEs of interest to atezo (Gr 3 increased lipase, Gr 2 hyperthyroidism, and Gr 1 infusion-related reaction). Common Gr 3-4 AEs during induction were: neutropenia (45%), febrile neutropenia (9.5%), leukopenia (5%), anemia (5%), increased lipase (5%), and fatigue (5%), and during consolidation were: neutropenia (10%), febrile neutropenia (3%), increased lipase (14%), and syncope (7%). Conclusions: The PET-CR rate with R-CHOP-atezo at EOI is encouraging and compares favorably with that previously reported with R-CHOP. The overall safety profile of R-CHOP-atezo is manageable, with no new safety signals reported. Preliminary MRD data at EOI are encouraging and support activity. Biomarker data and duration of response will be presented. Disclosures Younes: Sanofi: Honoraria; Roche: Honoraria, Research Funding; Takeda: Honoraria; Bayer: Honoraria; J&J: Research Funding; BMS: Honoraria, Research Funding; Astra Zeneca: Research Funding; Celgene: Honoraria; Novartis: Research Funding; Pharmacyclics: Research Funding; Seattle Genetics: Honoraria; Janssen: Honoraria, Research Funding; Abbvie: Honoraria; Genentech: Research Funding; Incyte: Honoraria; Merck: Honoraria; Curis: Research Funding. Burke:Tempus Labs: Consultancy; Celgene: Consultancy; Gilead: Consultancy; Genentech: Consultancy; Abbvie: Consultancy; Bayer: Consultancy; Seattle Genetics: Consultancy, Speakers Bureau. Cheson:AbbVie, Roche/Genentech, Pharmacyclics, Acerta, TG Therapeutics: Consultancy. Diefenbach:Genentech: Consultancy; Trillium: Research Funding; Millenium/Takeda: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Incyte: Research Funding; Merck: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Denovo: Research Funding; Acerta: Research Funding. Hawkes:Celgene: Other: Advisory board, Research Funding; Astra Zeneca: Research Funding; Merck: Other: Advisory board; Takeda: Other: Speaker fee; Roche: Other: Speaker fee; advisory board; Bristol Myers Squibb: Other: Speaker fee, Research Funding; Merck Sharpe Dohme: Research Funding; Merck KGA: Research Funding. Khan:Roche: Honoraria; AbbVie: Honoraria. Lossos:Affimed: Research Funding. Vitolo:Takeda: Speakers Bureau; Gilead: Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sandoz: Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Yuen:Seattle Genetics: Research Funding. Oestergaard:Roche: Employment, Other: Ownership interests PLC. Chitra:Genentech/Roche: Employment. Wenger:F. Hoffmann-La Roche Ltd: Employment, Equity Ownership, Other: Ownership interests PLC. Nielsen:F. Hoffmann-La Roche Ltd: Employment, Other: Ownership interests PLC. Sellam:Roche: Employment. Sharman:Pharmacyclics, an AbbVie Company: Consultancy, Research Funding; Acerta: Consultancy, Research Funding.

Introduction: Clinical trial response assessments for follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) typically mandate bone marrow biopsies (BMBs) at baseline and for confirmation of complete response (CR) as assessed by computed tomography (CT) imaging according to International Working Group (IWG) criteria. BMBs are painful and expensive, and can deter patients (pts) from clinical trial participation. Rutherford et al. (Br J Haematol 2017) suggested that confirmatory BMBs do not impact response assessment in the majority of FL pts treated in clinical trials. We describe the impact of confirmatory BMBs on response in the GALLIUM study (NCT01332968), which randomized previously untreated FL pts to obinutuzumab (G)- or rituximab (R)-chemotherapy (CHOP, CVP, or bendamustine) followed by maintenance with the same antibody in responders, and in the GOYA study (NCT01287741), which randomized previously untreated DLBCL pts to G-CHOP or R-CHOP. Methods: We conducted a retrospective analysis of GALLIUM and GOYA to evaluate the percentage of pts with CR as assessed by CT but with a positive BMB at end of induction (EOI), and the percentage of pts with complete metabolic response (CMR) on positron emission tomography (PET) by Lugano 2014 criteria but with a positive BMB at EOI. Response by PET was an exploratory endpoint and not mandatory. Results: Of 1202 randomized FL pts in GALLIUM, 633 (52.7%) had a positive (613 pts, 51.0%) or indeterminate (20 pts, 1.7%) baseline BMB (data missing for 12 pts, 1.0%). Bone marrow involvement was not prognostic for progression-free survival (PFS; investigator (INV)-assessed PFS: HR 0.99 [95% CI 0.80, 1.23] for pts with positive vs non-positive BMB). At EOI, 209/633 (33%) pts had a CR on CT by IWG criteria, 179 of whom had a follow-up BMB to confirm response; 174/179 (97.2%) had a negative BMB that confirmed CR, 1/179 (0.6%) was positive, and 4/179 (2.2%) were indeterminate. Overall, only 5/179 (2.8%) pts with a positive/indeterminate baseline BMB and EOI CR by CT, or 5/1202 (0.4%) pts enrolled in the trial, had a repeat BMB result that was relevant for response assessment. Lugano 2014 criteria (determined by Independent Review Committee; IRC) were used for response assessment in 282/633 (44.5%) pts with positive/indeterminate baseline BMBs and EOI PET scans available; 251/282 (89.0%) pts had a CMR, and 213/251 (84.9%) underwent confirmatory BMBs at EOI (203 [95.3%] negative, 5 [2.3%] positive, and 5 [2.3%] indeterminate). Thus, BMB results only affected response by Lugano 2014 in 4.7% of pts having a repeat BMB (0.8% of all enrolled pts). Of 1418 randomized DLBCL pts in GOYA, 167 (11.8%) had a positive (154 pts, 10.9%) or indeterminate (13 pts, 0.9%) baseline BMB; information was missing for 14 pts (1.0%). Bone marrow involvement was prognostic for PFS (INV-assessed PFS: HR 0.75 [95% CI: 0.56, 0.99]; 3-year PFS rate 55.3% vs 69.8% for pts with positive vs non-positive BMBs, respectively). At EOI, 69/167 (41.3%) pts had a CR on CT by IWG criteria, 49 of whom had a follow-up BMB to confirm response; 47/49 (95.9%) had a negative BMB and 2/49 (4.0%) were positive. Therefore, only 2/49 (4.0%) pts with a positive/indeterminate baseline BMB and EOI CR by CT, or 2/1418 (0.1%) pts enrolled in the GOYA trial, had a repeat BMB result that was relevant for response assessment. Lugano 2014 criteria (by IRC) were used for response assessment in 121/167 (72.5%) pts with positive/indeterminate baseline BMBs and EOI PET scans available; 96/121 (79.3%) pts had a CMR, and 70/96 (72.9%) underwent confirmatory BMB. Of these, 65/70 (92.9%) were negative. Thus, BMB results only affected response by Lugano 2014 in 7.1% of pts having a repeat BMB (0.4% of all enrolled pts). Conclusions: In previously untreated FL and DLBCL pts in the GALLIUM and GOYA studies, post-induction BMB results impacted the CR rate by IWG criteria in only a minority of pts ( Disclosures Hiddemann: Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; F. Hoffman-La Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Consultancy, Research Funding. Kostakoglu:Roche: Consultancy, Honoraria; Norvatis: Consultancy, Honoraria. Marcus:F. Hoffman-La Roche: Other: Travel support and lecture fees; Roche: Consultancy, Other: Travel support and lecture fees ; Gilead: Consultancy. Martelli:F. Hoffman-La Roche: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Sandoz: Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Membership on an entity's Board of Directors or advisory committees. Sehn:Roche/Genentech: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria. Trněný:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Advisory board; Sandoz: Honoraria; Incyte: Membership on an entity's Board of Directors or advisory committees, Other: Advisory board; Gilead: Honoraria; Abbvie: Honoraria, Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees, Other: Advisory board; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Advisory board; F. Hoffman-La Roche Ltd: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Advisory board, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Advisory board. Trotman:Janssen: Other: Unremunerated member of Ad Board, Research Funding; Beigene: Research Funding; PCYC: Research Funding; F. Hoffman-La Roche: Other: Travel to meeting, Unremunerated member of Ad Board, Research Funding; Celgene: Other: Unremunerated member of Ad Board, Research Funding; Takeda: Other: Unremunerated member of Ad Board. Vitolo:Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Gilead: Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Speakers Bureau. Nielsen:F. Hoffmann-La Roche Ltd: Employment, Other: Ownership interests PLC. Mattiello:Roche: Employment. Sahin:F. Hoffman-La Roche Ltd: Other: Ownership interests PLC. Sellam:Roche: Employment. Martin:Seattle Genetics: Consultancy; Bayer: Consultancy; AstraZeneca: Consultancy; Kite: Consultancy; Janssen: Consultancy; Gilead: Consultancy.

Introduction: Standard of care for previously untreated patients (pts) with diffuse large B-cell lymphoma (DLBCL) is rituximab (R) plus 6-8 cycles of CHOP (R-CHOP). While the RICOVER trial (Pfreundschuh et al. Lancet Oncol 2008) showed no benefit of 6 versus 8 cycles of R-CHOP administered at 2-weekly intervals, this has not been assessed with the standard 3-weekly regimen, and many centers continue to administer 8 cycles. GOYA (NCT01287741) was an open-label, randomized, Phase III study of the efficacy and safety of R-CHOP versus obinutuzumab (GA101; G) plus CHOP in previously untreated pts with DLBCL. The current exploratory analysis compared investigator (INV)-assessed progression-free survival (PFS) and overall survival (OS) in pts receiving 6 or 8 cycles of CHOP in combination with 8 cycles of R in GOYA. Methods: Eligible pts were aged ≥18 years with histologically documented, CD20-positive DLBCL and ≥1 bi-dimensionally measurable lesion, ECOG PS 0-2, IPI score ≥2, and adequate hematologic function. Low-risk pts with IPI score 1 not due to age alone or 0 with bulky disease (1 lesion ≥7.5cm) were also eligible. Pts who were randomized to R-CHOP received 8 cycles of R (375mg/m2) in combination with 6 (CHOP6) or 8 (CHOP8) cycles of CHOP. Centers elected upfront to administer either 6 or 8 CHOP cycles to all pts enrolled at that site. Efficacy was evaluated in all pts who were randomized to R-CHOP (intent-to-treat population; data cut-off: January 31, 2018). Safety was assessed in all pts who completed the 6th treatment cycle and received R in the 7th cycle (CHOP6 safety population: no additional CHOP cycles; CHOP8 safety population: at least 7 or 8 CHOP cycles received). Only AEs starting during or after the 7th cycle were considered. Statistical analyses included Kaplan-Meier estimates and Cox-regression, with and without propensity score adjustment to correct for baseline imbalances. Results: Results are reported for 712 pts who were randomized to R-CHOP (CHOP6, n=526; CHOP8, n=186; safety population: CHOP6, n=461; CHOP8, n=144). In the CHOP6 group, 55% were male and median age was 62 years (range 54-70). In CHOP8, 49% were male and median age was 60 years (range 47-67). Baseline characteristics were broadly comparable across treatment groups, except for geographic region (CHOP6 vs CHOP8: Asia, 32% vs 49%, respectively; Eastern Europe, 10% vs 24%; Western Europe, 36% vs 13%; North America, 18% vs 8%; other, 4% vs 5%). In CHOP6, 89% completed 6 cycles of R-CHOP, while in CHOP8, 76% completed 8 cycles. Three-year INV-assessed PFS rates were comparable between groups: 68.7% in CHOP6 versus 66.8% in CHOP8 (HR 0.92; 95% CI: 0.69, 1.23; Figure 1a). Three-year OS rates appeared higher in the CHOP6 group (83.2% vs 76.2% in CHOP8; HR 0.65; 95% CI: 0.46, 0.91; Figure 1b). PFS and OS comparisons were unchanged after propensity score adjustment for the prespecified baseline characteristics, including age, gender, disease stage, geographic region, IPI score, extranodal sites, body surface area, bulky disease, LDH, and COO (PFS: HR 0.96, 95% CI: 0.70, 1.32; OS: HR 0.66, 95% CI: 0.45, 0.97). Interim treatment response (by CT) did not influence these findings. Model-based subgroup analysis according to baseline pt characteristics did not identify any pt subgroups benefitting from 8 versus 6 cycles of CHOP (Figure 1c). Incidence of grade 3-5 adverse events (AEs) was lower in the CHOP6 group than in the CHOP8 group (17.8% vs 38.9%, respectively); cardiac AEs (all grade: 2.4% vs 6.3%; grade 3-5: 1.3% vs 3.5%) and infections (all grade: 10.6% vs 23.6%) were also less common. In support of these findings, similar results were achieved after repeating the same efficacy analysis in pts who received 6 or 8 cycles of CHOP in combination with 8 cycles of obinutuzumab. Conclusions: In this exploratory analysis of 712 previously untreated DLBCL pts in GOYA, in which the number of CHOP cycles was selected upfront by each site, no additional PFS benefit was observed with 8 cycles of R-CHOP compared with 6 cycles of R-CHOP plus 2 cycles of R, even after adjusting for baseline differences, including COO and IPI. Slow response, assessed by interim CT, did not influence these findings. Furthermore, incidence of grade 3-5 AEs (including cardiac) and any grade infections was markedly higher in pts receiving 8 cycles of CHOP versus 6 cycles. These results suggest that rituximab with 6 cycles of 3-weekly CHOP should be considered standard of care. Disclosures Sehn: Janssen: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Roche/Genentech: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria. Culligan:JAZZ: Honoraria; Celgene: Other: Support to attend conferences; Takeda: Honoraria, Other: Support to attend conferences; Daiichi-Sankyo: Other: Support to attend conferences; Abbvie: Other: Support to attend conferences; Pfizer: Honoraria; Merck Sharp & Dohme (MSD): Honoraria. Ogura:Cellgene: Honoraria; Celltrion: Research Funding; Takeda: Honoraria; SymBio: Research Funding. Launonen:Roche: Employment, Other: Travel, accommodation, expenses; Novartis: Consultancy, Equity Ownership, Other: Ownership interests none PLC; Travel. accommodation, expenses; Launonen: Other: Ownership interests none PLC; Travel, accommodation, expenses. Nielsen:F. Hoffmann-La Roche Ltd: Employment, Other: Ownership interests PLC. Sellam:Roche: Employment. Trněný:Morphosys: Membership on an entity's Board of Directors or advisory committees, Other: Advisory board; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Advisory board; Incyte: Membership on an entity's Board of Directors or advisory committees, Other: Advisory board; F. Hoffman-La Roche Ltd: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Advisory board, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Advisory board; Gilead: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Advisory board; Sandoz: Honoraria; Abbvie: Honoraria, Research Funding. Vitolo:Gilead: Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sandoz: Speakers Bureau. Martelli:Servier: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Membership on an entity's Board of Directors or advisory committees; Sandoz: Membership on an entity's Board of Directors or advisory committees; F. Hoffman-La Roche: Membership on an entity's Board of Directors or advisory committees.

Introduction: Quantitative 18fluorodeoxyglucose positron emission tomography (PET)/computed tomography assessment using total metabolic tumor volume (TMTV) and tumor lesion glycolysis (TLG) measurements has been found promising as an objective method to predict survival in diffuse large B-cell lymphoma (DLBCL) patients (pts). However, the methodology for PET-derived metrics is still evolving, and their predictive value is yet to be proven in large-scale, prospective, multicenter studies. We investigated the prognostic value of baseline maximum standardized uptake value (SUVmax), TMTV and TLG for progression-free survival (PFS) in a large pt cohort treated with obinutuzumab (GA101; G) or rituximab (R) combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in the Phase 3 GOYA study (NCT01287741; Vitolo et al. J Clin Oncol 2017). Methods: Pts aged ≥18 years, with previously untreated, CD20-positive DLBCL and an International Prognostic Index (IPI) score ≥2 and low-risk pts with IPI scores of 1 (not due to age alone) or 0 (with bulky disease) were randomized 1:1 to receive 8 x 21-day cycles of G (1000mg intravenous [IV] on Days [D] 1, 8, and 15 of Cycle [C] 1 and D1, C2-8) or R (375mg/m2 IV on D1, C1-8) plus 6 or 8 cycles of CHOP. All pts had a baseline and end of treatment (EOT) PET. PET images were segmented using an automated workflow program in MIM software, applying thresholds of 1.5 x liver background and a minimum volume of 1mL to the whole body PET images. The data were analyzed for the overall population and according to germinal center B-cell-like (GCB), unclassified, and activated B-cell-like (ABC) subtypes of DLBCL. TMTV, TLG, and SUVmax were split into 4 categories/levels according to the following quartiles: Q1, Results: Of 1418 enrolled pts, 1346 had a baseline PET scan and 1334 had detectable lesions. There was no statistical difference in PFS between the treatment arms (G vs R), thus the entire cohort was analyzed as a whole. Results of the predictive value of baseline TMTV for PFS are presented in quartiles in Figure 1, and results of the predictive value of TLG for PFS are presented in quartiles in Figure 2, for the overall PET intent-to-treat population. After a median follow-up of 29 months TMTV and TLG were highly predictive of PFS when comparing Q4 vs Q1: HR=2.21, 95% CI 1.48-3.29, p Three-year PFS for pts in TMTV Q1, 2, 3 and 4 was 86% (95% CI 81-89%), 84% (95% CI 78-88%), 78% (95% CI 72-83%) and 66% (95% CI 59-71%), respectively. TMTV also showed a trend for a better prediction of PFS (Figure 3) and OS in pts with the unclassified and ABC DLBCL subtypes when compared with those with the GCB subtype. Conclusions: This large prospective study confirms baseline TMTV and TLG as predictors of PFS and OS in DLBCL after first-line immunochemotherapy, while SUVmax may not be a predictor. Furthermore, TMTV and TLG appear to be better predictors of survival for pts with the unclassified and ABC subtypes of DLBCL than for those pts with the GCB subtype. Further analyses are underway comparing these results with the predictive value of percentage change from baseline to EOT PET, Deauville score-based analysis of EOT PET, and the various molecular DLBCL subtypes. Figure 1 Figure 1. Disclosures Kostakoglu: Roche: Consultancy, Other: GOYA is sponsored by F. Hoffmann-La Roche Ltd. Third-party editorial support, under the direction of Lale Kostakoglu and Denis Sahin, was provided by Helen Cathro of Gardiner-Caldwell Communications, and was funded by F. Hoffmann-La Roche Ltd. Sehn: Celgene: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Roche/Genentech: Consultancy, Honoraria. Chua: Lundbeck: Honoraria; Roche: Honoraria; Seattle Genetics: Honoraria; Gilead Sciences: Honoraria; Merck: Honoraria. Gonzalez-Barca: Gilead: Consultancy; Sandot: Consultancy; Janssen: Speakers Bureau; Roche: Speakers Bureau. Pinto: Millenium Takeda: Research Funding; Gilead: Honoraria; Roche: Honoraria; Bristol Myers Squibb: Honoraria; Merck Sharp Dome: Honoraria; Celgene: Honoraria; Helssin: Honoraria; Mundipharma EDO: Speakers Bureau. Fingerle-Rowson: F. Hoffmann-La Roche Ltd: Employment, Equity Ownership. Knapp: Roche: Employment. Mattiello: Roche: Employment. Nielsen: F. Hoffmann-La Roche Ltd: Employment, Equity Ownership. Sellam: Roche: Employment. Sahin: Roche: Employment, Equity Ownership. Vitolo: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria; Mundipharma: Honoraria; Takeda: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Trněný: Janssen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding.

UNLABELLED There is an impressive body of knowledge on pain management in infants hospitalized in neonatal intensive care units. However, deficits in the clinical management of pain in these infants remain. One reason is the gap between research evidence and translation of this knowledge into the clinical setting. This is particularly true for non-pharmacological pain-relieving methods. Effective performance of some of these methods requires additional staffing and time. This viewpoint articles describes the clinical challenges associated with implementing 'facilitated tucking'. Although 'facilitated tucking' is described as an efficient method for acute pain relief, the clinical facilitators required to successfully implement such a resource consuming-intervention remain unclear. CONCLUSION Translational research on the feasibility of using 'facilitated tucking' in the management of neonatal pain is warranted, including the economic impact of this intervention. Increased manpower costs need to be weighed against the possible long-term economical consequences of pain exposure in infants.

Major efforts to develop objective measurement tools for neonatal pain assessment have been made. However, the challenge of measuring pain in neonates remains suggesting that contextual factors (cFs) might alter their responses to pain. Although the role of cFs is increasingly discussed as crucial for pain assessment, they are not well described in the literature and are rarely considered in the clinical setting despite their importance. Aim To systematically examine studies investigating the impact of cFs on pain response in preterm infants. Method A literature search was undertaken for the period from 1990 to 2009. Studies reporting the relation between one or more cFs and pain response in preterm infants during a heelstick procedure were considered for inclusion. Results Twenty-three studies satisfied inclusion criteria. The studies varied relative to their design, sample, analysis procedures, and variables examined. Six categories of cFs emerged: age, pain exposure, health status, therapeutic interventions, behavioral status, and demographic factors. The examined cFs varied in the strength of their association with pain response, although none were invariably related, as evidenced by contradictory findings. In some cases the inconsistencies appeared attributable to methodological limitations in studies. Behavioral and physiological pain responses were not always in agreement as would be expected. Conclusion This review supports the influence of some cFs on pain response. However, the results remain inconclusive which may be, in part, related to the heterogeneity of the studies. Contextual factors need further investigation for a better understanding of the magnitude of their effect on pain response.

1168 Contextual Factors Influencing Pain Response to Heel Stick Procedure in Preterm Infants: What Do We Know? a Systematic Review