Abstract: Patients with non–Hodgkin lymphoma and chronic lymphocytic leukemia (NHL/CLL) elicit inadequate antibody responses after initial SARS-CoV-2 vaccination and remain at high risk of severe COVID-19 disease. We investigated IgG, IgA, and IgM responses after booster vaccination against recent SARS-CoV-2 variants including Omicron BA.5 in 67 patients. Patients had lower fold increase and total anti-spike binding titers after booster than healthy individuals. Antibody responses negatively correlated with recent anti-CD20 therapy and low B-cell numbers. Antibodies generated after booster demonstrated similar binding properties against SARS-CoV-2 variants compared with those generated by healthy controls with lower binding against Omicron variants. Importantly, 43% of patients showed anti-Omicron BA.1 neutralizing antibodies after booster and all these patients also had anti-Omicron BA.5 neutralizing antibodies. Patients with NHL/CLL demonstrated inferior antibody responses after booster vaccination, particularly against Omicron variants. Prioritization of prophylactic and treatment agents and vaccination of patients and close contacts with updated vaccine formulations are essential. Significance: Limited data exist on antibody responses against current SARS-CoV-2 variants after booster vaccination in patients with NHL/CLL. We showed inferior antibody responses against Omicron variants after booster vaccination in these patients but some generated anti-Omicron titers. This stresses the importance of vaccinating patients with updated formulations.

Abstract: Background: In patients with chemo-sensitive relapsed diffuse large B-cell lymphoma (DLBCL), autologous hematopoietic cell transplant (ASCT) has long been the standard of care. Several recent studies have identified patient groups with poor post-transplant outcomes and in recent years chimeric antigen receptor (CAR)-T therapy has been utilized in patients who do not have adequate disease control to proceed with ASCT or who progress after ASCT. We hypothesized that the availability of CART to treat patients with aggressive lymphoma who were not ideal candidates for ASCT would lead to improved survival among lymphoma patients proceeding to transplant. We evaluated whether the demographics, baseline characteristics and post-ASCT outcomes for patients with relapsed non-Hodgkin lymphoma (NHL) have changed in the CAR-T era. Methods: We included patients initially diagnosed with DLBCL since 2012 who subsequently relapsed and received ASCT. Patients who completed ASCT without a documented relapse or who received CART therapy prior to an ASCT were excluded as were patients without adequate follow-up data. Patients who completed ASCT prior to January 1, 2018, were part of the pre-CART group while those completing ASCT on January 1, 2018 and later were part of the post-CART group. We compared demographics as well as disease and treatment-related variables of interest between the pre- and post-CART groups using Fisher's Exact or chi Square tests as appropriate for categorical and ANOVA for numeric variables. In addition, we determined progression-free (PFS) and overall survival (OS) from the date of ASCT using the Kaplan-Meier method and determined predictors of post-ASCT PFS and OS using the Cox Proportional Hazards model with backward elimination. Results: Of 84 included patients, 55 were in the pre-CART group and 29 were in the post-CART group. Median age at diagnosis for all patients was 55 years (range 22-73). 50 were male, and 60 had stage 3 or 4 disease. While there were no differences in demographics based on treatment group, the ECOG performance status for patients in the post-CART group was improved compared to those pre-CART (Table 1, p=0.040). There was also no difference in time from diagnosis to transplant between the two groups (Table 1, p=0.292). With a median follow-up post ASCT of 2.22 years for the pre-CART group and 1.24 years for the post-CART group, the median OS was 4.7 years (95% CI: 3.4 - Not Reached) for the entire cohort, 4.7 years (95% CI: 2.8 - Not Reached) for the pre-CART group and not reached (95% CI: NR-NR) for the post-CART group. The median PFS was not reached in either cohort (p=0.932). Neither univariate nor multivariable analysis showed any of covariates as being significant predictors of post-ASCT PFS. In the multivariable model for OS, receiving R-CHOP chemotherapy compared to other induction regimens (HR 0.28 [0.10-0.74], p=0.01) predicted improved OS while increased age (HR 1.06 [1.01-1.11] , p=0.03) predicted inferior OS. The receipt of ASCT after CART cell era, conditioning regimen, or first salvage regimen all did not impact PFS or OS. Conclusion: In comparison with those patients receiving autologous transplantation prior to the adoption of CAR T cell, patients receiving ASCT more recently had no change PFS or OS despite having better performance status prior to ASCT. Our findings suggest that selection of appropriate candidates for ASCT in the current era is critical and that patients who are at higher risk for early post-ASCT relapse should be considered for novel approaches including immune effector cell therapy. Additional follow-up will be needed to determine if newer currently approved therapies for post-ASCT relapse can improve OS in relapsed/refractory DLBCL who relapse after ASCT. Disclosures Waller: Verastem Oncology, Inc: Consultancy, Research Funding. Allen:Curio Sciences: Honoraria; Bayer: Consultancy, Other; Clinical Care Options: Speakers Bureau; Research to Practice: Speakers Bureau; Imbrium: Consultancy, Other. Lonial:JUNO Therapeutics: Consultancy; Amgen: Consultancy, Honoraria, Other: Personal fees; Abbvie: Consultancy; Sanofi: Consultancy; Karyopharm: Consultancy; Genentech: Consultancy; Onyx: Honoraria; Janssen: Consultancy, Honoraria, Other: Personal fees, Research Funding; Takeda: Consultancy, Other: Personal fees, Research Funding; Novartis: Consultancy, Honoraria, Other: Personal fees; BMS: Consultancy, Honoraria, Other: Personal fees, Research Funding; GSK: Consultancy, Honoraria, Other: Personal fees; Merck: Consultancy, Honoraria, Other: Personal fees; Millennium: Consultancy, Honoraria; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees. Kaufman:Tecnopharma: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; AbbVie: Consultancy; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi/Genyzme: Consultancy, Honoraria. Hofmeister:Janssen: Honoraria, Research Funding; Oncolytics Biotech: Research Funding; Imbrium: Honoraria; Oncopeptides: Honoraria; Bristol Myers Squibb: Honoraria, Research Funding; Nektar: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Karyopharm: Honoraria, Research Funding. Dhodapkar:Janssen: Membership on an entity's Board of Directors or advisory committees, Other; Kite: Membership on an entity's Board of Directors or advisory committees, Other; Lava Therapeutics: Membership on an entity's Board of Directors or advisory committees, Other; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Other; Amgen: Membership on an entity's Board of Directors or advisory committees, Other; Roche/Genentech: Membership on an entity's Board of Directors or advisory committees, Other. Nooka:Oncopeptides: Consultancy, Honoraria; Spectrum Pharmaceuticals: Consultancy; Celgene: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; Adaptive Technologies: Consultancy, Honoraria; Karyopharm Therapeutics, Adaptive technologies: Consultancy, Honoraria, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Other: Personal Fees: Travel/accomodations/expenses, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding. Klisovic:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees. Langston:Bristol Myers Squib: Research Funding; Incyte: Research Funding; Jazz Pharmaceuticals: Research Funding; Astellas Pharmaceuticals: Research Funding; Kadmon Corporation: Research Funding; Takeda: Research Funding; Chimerix: Research Funding. Cohen:Janssen, Adicet, Astra Zeneca, Genentech, Aptitude Health, Cellectar, Kite/Gilead, Loxo: Consultancy; Genentech, BMS, Novartis, LAM, BioInvent, LRF, ASH, Astra Zeneca, Seattle Genetics: Research Funding.

Abstract: Background: Maintenance rituximab administered post autologous stem cell transplant (ASCT) in mantle cell lymphoma (MCL) is associated with improved overall survival (OS). Maintenance approaches with the proteasome inhibitor, bortezomib, are associated with improved progression-free survival (PFS), although its use is limited by peripheral neuropathy (Kaplan et al, 2020). We conducted a phase 1 study to evaluate the safety of maintenance therapy with ixazomib, an oral proteasome inhibitor, alone and in combination with rituximab for patients with MCL completing ASCT in first remission. Methods: Adult patients with MCL completing an ASCT in first partial or complete remission and who remained progression-free were enrolled between days 70-180 post-ASCT. Initially, patients received ixazomib monotherapy in cohorts of three using a standard 3+3 design. Patients self-administered ixazomib on days 1, 8, and 15 of each 28-day cycle at one of 3 dose levels: 2.3mg, 3mg, or 4mg. Patients continued therapy until disease progression, intolerance, or completion of 10 cycles. While we were enrolling to the 4mg dose level, the LYMA trial reported an OS benefit associated with maintenance rituximab (Le Gouill et al, 2017), so the protocol was amended to explore the combination of ixazomib and rituximab. Combination therapy consisted of ixazomib 4mg (given at the same schedule) and rituximab 375 mg/m2 given on day 1 of cycles 1, 3, 5, 7, and 9. The primary objective of the study was to evaluate the safety of this treatment and determine the maximum tolerated dose (MTD) while secondary objectives included efficacy. Results Twelve patients enrolled in the trial and received at least one dose of study therapy. Seven patients received ixazomib monotherapy (3mg = 3 patients, 4mg= 4 patients), and 5 patients received combination with rituximab and 4mg ixazomib. In all patients, the median age was 58 years (range 42-73 years) and 75% of the patients were male. Five patients had a high risk MIPI score. All patients entered the study in complete remission. Pre-transplant induction was R-HyperCVAD (n=6), VR-CAP/R-DHAP (n=2), NORDIC regimen (n=2), R-CHOP/R-DHAP (n=1), and R-DHAX (n=1). Transplant conditioning regimens were BEAM (n=7) or Bu/Cy/VP-16 (n=5). In the monotherapy group, 6 patients completed all 10 cycles of therapy. One patient experienced a dose limiting toxicity (DLT) which consisted of grade 3 neutropenia following cycle 1. In addition to the patient who experienced a DLT, one patient discontinued therapy early due to persistent abdominal pain that was ultimately determined to be unrelated to study therapy after an extensive evaluation. Two patients required dose reductions due to grade 3 hematologic toxicities. Two patients in the combination therapy group completed 10 cycles of therapy. Two patients experienced DLTs which consisted of grade 4 neutropenia, and 1 patient opted to discontinue therapy early due to persistent grade 2 peripheral neuropathy. In all patients, common adverse events (AEs) regardless of attribution were abdominal pain (n=6), leukopenia (n=5), nausea (n=4), thrombocytopenia (n=4), and peripheral neuropathy (n=3). Grade 3/4 AEs were thrombocytopenia (n=1) and neutropenia (n=4). No grade 3/4 peripheral neuropathy was observed. With a median follow up of 29.6 months, no patients experienced disease progression and all are alive. Due to the myelosuppression-related DLT's encountered in the combination arm, the study was closed to further accrual. Conclusions Our findings suggest adding rituximab to ixazomib at the evaluated dose and schedule as post-ASCT maintenance is associated with myelosuppression, and we would suggest future studies evaluate an alternative dose/schedule to mitigate this risk. The lack of early progressions is encouraging, confirming the findings from CALGB50403 that proteasome inhibition may provide therapeutic benefit in this setting. Further evaluation of rituximab-containing post-induction combination therapies may identify a safer dosing strategy while improving long-term remission rates. Disclosures Allen: Bayer: Consultancy, Other; Curio Sciences: Honoraria; Clinical Care Options: Speakers Bureau; Research to Practice: Speakers Bureau; Imbrium: Consultancy, Other. Waller:Verastem Oncology, Inc: Consultancy, Research Funding. Flowers:Bayer: Consultancy; Denovo Biopharma: Consultancy; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; BeiGene: Consultancy; Celgene: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Karyopharm: Consultancy; OptumRx: Consultancy; Pharmacyclics/Janssen: Consultancy; Spectrum: Consultancy; Acerta: Research Funding; Millennium/Takeda: Consultancy, Research Funding; TG Therapeutics: Research Funding; Burroughs Wellcome Fund: Research Funding; Eastern Cooperative Oncology Group: Research Funding; National Cancer Institute: Research Funding; V Foundation: Research Funding; Cancer Prevention and Research Institute of Texas: Research Funding; Kite: Research Funding; Leukemia and Lymphoma Society: Membership on an entity's Board of Directors or advisory committees. Cohen:Genentech, BMS, Novartis, LAM, BioInvent, LRF, ASH, Astra Zeneca, Seattle Genetics: Research Funding; Janssen, Adicet, Astra Zeneca, Genentech, Aptitude Health, Cellectar, Kite/Gilead, Loxo: Consultancy.

Abstract: Background: Allogeneic hematopoietic transplantation (HCT) is frequently considered for patients (pts) with relapsed T-cell lymphoma (TCL) and less often as consolidation of initial therapy. Outcomes from prior registry data show that only 31% of pts remain disease free 3 years after HCT (Smith et al. JCO 2013). However, several single institution studies have superior outcomes. We previously presented an analysis of allogeneic transplant in T-cell lymphoma but have expanded this effort to 12 academic centers with longer follow up (Mehta-Shah ASH 2017). Methods: We analyzed the patient characteristics at time of diagnosis and transplant, treatment history, overall (OS) and progression-free survival (PFS) in consecutive TCL pts who had an HCT from 1/1/2000-12/31/2019 at 12 academic institutions. Results: Patient characteristics are shown in Table 1. 508 pts were identified with median age 51 years (16 - 72). 452 (86.5%) had known remission status at the time of HCT: 245 (54.4%) complete remission (CR), 168 (37.2%) partial remission (PR), 23 (5.0%) stable disease (SD), 16 (3.2%) progressive disease (PD). Seventy-eight (15.5%) had a prior autologous HCT. Thirty-six (7%) pts underwent HCT in CR1, 352 (69%) for relapsed/refractory TCL, and was not specified in 120 pts (24%). The median HCT comorbidity index (HCT-CI) score was 1 (0-11). Conditioning regimens were myeloablative (n=180), reduced intensity/non-myeloablative (n=323), unknown (n=3). Donor type was known for 471 pts: 192 matched related (MRD), 183 matched unrelated (MUD), 53 mismatched (MMD), 18 haploidentical donors, 25 umbilical cord blood. In this series, the 2 year OS and PFS rate following HCT were 59.1% (95%CI: 54.6-63.3%) and 45.8% (95%CI: 41.3-50.2%) respectively. 5 year OS and PFS rate were 50.8% (95%CI: 46.1-55.3%) and 39.4% (95%CI: 34.9-43.9%) (Fig 1) For disease specific 2-year and 5-year PFS, see Table 1. At a median follow-up of 29.7 mo (0.1-263 mo), 163 pts had relapsed and 261 pts had died. The median time from relapse post HCT to death was 10.2 mo (0-158.4 mo). Of 261 deaths: 81 were due to transplant related mortality (TRM), 69 were confirmed to be from TCL, and 111 were from non-relapse mortality/unknown. There was not a significant difference in PFS for pts with AITL, PTCL-NOS, ALK positive ALCL or ALK negative ALCL, with median PFS of 23.2 mo (95%CI:15.3-64.2). However, when AITL was compared specifically to PTCL-NOS or ALCL, those with AITL had a trend towards improved median PFS (51.4 mo vs. 18.4 mo, p=0.14) and improved median OS (not reached vs. 73.1 mo, p=0.26). At 5 years, PFS was worse for CTCL (18.6%, 95% CI: 9.7%-30.0%) compared to PTCL subtypes (43.8%; 95% CI: 37.3%-50.0%)(p & lt;0.001) . However, 5-year OS was similar for CTCL (44.0%, 95% CI: 30.1-56.4%) and PTCL (53.1%, 95% CI: 46.5-59.3%) (p=0.46). The rate of TRM at 1 year was 11.2% (95%CI:8.5%-14.0%). Of evaluable pts, 245/489 (46%) had acute GvHD and 192/473 (40.6%) had chronic GvHD. There were no differences in TRM according to recipient age (p=0.47). Higher HCT-CI was associated with an increased risk of TRM (HR 1.15, 95% CI: 1.031-1.286; p=0.012) Disease status at the time of HCT was associated with PFS (p & lt;0.001). Median PFS for those with CR (n=239), PR (n=164), SD (n=22) or PD (n=14) were 44.6 mo, 8.6 mo, 21 mo, 3.5 mo respectively. Degree of donor match was associated with cumulative TRM (p=0.0241). For pts who underwent MRD, MUD, or MMD HCT, cumulative TRM at 12 months was 8% (95%CI: 5.5-12.2%), 13.1% (95%CI: 9.7-17.8%), 14.7% (95%CI: 8.7-24.6%). Conclusions: We present the largest series of HCT in TCL. In this dataset, HCT provided durable disease control for a significant portion of pts with relapsed or refractory or otherwise high risk TCL. Depth of response to therapy immediate prior to HCT was associated with PFS. Patients with AITL appeared to have a trend towards improved outcome with HCT compared to other common PTCL histologies. Patients with CTCL had a higher rate of relapse compared to PTCL subtypes, but OS was similar. MRD HCTs were associated with lower TRM. This data supports the curative potential of HCT in a patient group with otherwise poor survival and limited treatment options. Disclosures Mehta-Shah: Corvus: Research Funding; Genetech/Roche: Research Funding; Verastem: Research Funding; Karyopharm Therapeutics: Consultancy; Bristol Myers-Squibb: Research Funding; Celgene: Research Funding; C4 Therapeutics: Consultancy; Kyowa Hakko Kirin: Consultancy; Innate Pharmaceuticals: Research Funding. Dahi:Kite: Consultancy. Sauter:Sanofi-Genzyme: Consultancy, Research Funding; Kite - a Gilead Company: Consultancy; Spectrum Pharamaceuticals: Consultancy; Gamida Cell: Consultancy; GSK: Consultancy; Bristol-Myers Squibb: Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy; Genmab: Consultancy; Precision Biosciences: Consultancy, Research Funding; Juno Therapeutics: Consultancy, Research Funding. Moskowitz:Merck: Research Funding; Imbrium Therapeutics, L.P.: Consultancy; Bristol-Myers Squibb: Research Funding; Miragen Therapeutics: Consultancy; Merck: Consultancy; Seattle Genetics: Consultancy; Incyte: Research Funding; Seattle Genetics: Research Funding. Jacobsen:Novartis: Research Funding; Takeda: Honoraria; Pharmacyclics: Research Funding; F. Hoffmann-LaRoche: Research Funding; Astra-Zeneca: Consultancy; Acerta: Consultancy; Merck: Consultancy. William:Celgene: Consultancy, Honoraria; Guidepoint Global: Consultancy; Seattle Genetics: Research Funding; Dova: Research Funding; Incyte: Research Funding; Merck: Research Funding; Kyowa Kirin: Consultancy, Honoraria. Barta:Monsanto: Consultancy; Pfizer: Honoraria; Janssen: Honoraria; Seattle Genetics: Honoraria, Research Funding; Atara: Honoraria. Allen:Clinical Care Options: Speakers Bureau; Curio Sciences: Honoraria; Research to Practice: Speakers Bureau; Imbrium: Consultancy, Other; Bayer: Consultancy, Other. Song:Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen, Celgene,Takeda: Consultancy, Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Research Funding; Otsuka: Honoraria. Ruan:Celgene: Consultancy, Research Funding; Seattle Genetics: Research Funding; Kite Pharma: Consultancy; Juno: Consultancy; BMS: Consultancy, Research Funding; Pharmacyclics: Research Funding; AstraZeneca: Consultancy, Research Funding. McKinney:Kite/Gilead: Honoraria, Speakers Bureau; Kite/Gilead, Seattle Genetics, Molecular Templates, BTG, Pharmacyclics, Verastem, Genentech, Inc., Celgene: Consultancy; UNUM, Molecular Templates, Incyte, Beigene, Denovo Biopharma, Pharmacyclics, Nordic Nanovector, BMS, Genentech, Inc., Celgene: Research Funding. Beaven:Tessa Therapeutics: Research Funding; Roche: Research Funding; Seattle Genetics: Research Funding; MorphoSysAb: Research Funding; LoxoOncology: Research Funding; Celgene: Research Funding. Haverkos:Viracta THerapeutics: Consultancy. Alpdogan:Seattle Genetics: Consultancy; Kiowa Kirin: Consultancy. Porcu:Kiowa Kirin: Research Funding; Kura Oncology: Research Funding; Innate Pharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Galderma: Research Funding; Daiichi: Consultancy, Honoraria; Celgene: Research Funding; Cell Medica: Research Funding; Miragen: Research Funding; Verastem: Consultancy; Viracta Therapeutics: Membership on an entity's Board of Directors or advisory committees. Horwitz:Daiichi Sankyo: Research Funding; GlaxoSmithKline: Consultancy; Janssen: Consultancy; Kura Oncology: Consultancy; Myeloid Therapeutics: Consultancy; Miragen: Consultancy; ADCT Therapeutics: Consultancy, Research Funding; Aileron: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Forty Seven: Consultancy, Research Funding; Infinity/Verastem: Research Funding; Kyowa Hakka Kirin: Consultancy, Research Funding; Millenium/Takeda: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Trillium: Consultancy, Research Funding; Corvus: Consultancy; Innate Pharma: Consultancy; Mundipharma: Consultancy; Portola: Consultancy, Research Funding; Beigene: Consultancy; C4 Therapeutics: Consultancy; Verastem: Consultancy, Research Funding; Vividion Therapeutics: Consultancy; Affirmed: Consultancy; ASTEX: Consultancy.

Abstract: Bendamustine-rituximab (BR) is a standard of care for patients with mantle cell lymphoma (MCL) with median progression free survival (PFS) of approximately 3 years. Venetoclax has proven activity both as a single agent and in combination with other targeted therapies in relapsed MCL. We developed a phase 2 study of bendamustine, obinutuzumab, and venetoclax (BOV) for untreated patients with MCL to determine the efficacy and toxicity of this combination (NCT03872180). Patients ≥ 18 years old with untreated MCL received up to six 28-day cycles of BOV, consisting of bendamustine (90mg/m2 on D1-2) and obinutuzumab (1000mg, C1: D 1,8,15 and C2-6: D1) with a venetoclax ramp up from 20mg to 200mg during the first cycle and then 400mg on days 1-10 of cycles 2-6. Post-induction therapy is determined by the treating physician and is not dictated by the study. The primary endpoint was CR rate at the end of induction, per Lugano criteria. We assumed a historical CR rate of 60% with BR, with a goal CR rate of 85% with the BOV regimen and plan to accrue 23 total patients to assess for this difference. This was a two-stage design that included 9 patients in stage 1 with a requirement of 7 CR's in the first 9 patients to justify continued accrual. Secondary and correlative endpoints include PFS/overall survival, toxicity (including frequency and severity of tumor lysis syndrome), and MRD negativity using both commercial IgHTS assays as well as CAPP-Seq. Supportive care included G-CSF, antimicrobial prophylaxis, and prescribed monitoring for and management of tumor lysis syndrome. 11 patients have initiated therapy. Median age is 70 years (45-80), with 7 males and 4 females. All 11 patients had marrow involvement. Five patients had Ki67 index ≥30%, and TP53/17p abnormalities were found in 2 patients. Eight patients have completed 6 cycles, one patient discontinued study therapy after 5 cycles due to thrombocytopenia and 2 patients remain on therapy after 5 cycles of treatment. Of 9 patients who have completed end of treatment restaging, the ORR was 100%, including 8 CR's (89%) and 1 PR. The two patients currently completing study therapy have completed their interim PET/CT's and both have achieved CR. Three patients experienced grade 3+ obinutuzumab infusion reactions on cycle 1 day 1, with both patients requiring admission but subsequently fully recovering. One of these patients chose to forgo additional obinutuzumab while a second patient safely completed 6 cycles of treatment. The third patient initiated treatment in the hospital and experienced atrial fibrillation requiring ICU transfer, as well as grade 2 hyperkalemia while receiving day 1 treatment. Cardiology did not feel AFib was a result of TLS. She was ultimately able to safely complete 6 cycles of obinutuzumab. Although this event was not clear clinical TLS, the protocol was subsequently amended to incorporate venetoclax administration beginning on day 8 of cycle 1 to prevent overlapping infusional and TLS toxicities from venetoclax and obinutuzumab on day 1. No other patients have had TLS to date. Grade 3/4 hematologic toxicities include neutropenia (n=4), anemia (n=1), thrombocytopenia (n=4) leukopenia (n=3), and lymphopenia (n=10). Grade 3/4 non-hematologic toxicities included rash (n=2), hypophosphatemia (n=2). One patient has experienced prolonged leukopenia 2 months after finishing 6 cycles of therapy and was unable to collect stem cells after cycle 4 for a planned post-induction autologous transplant. To date, 2 patients have relapsed at 7 and 8 months after completing therapy, and one patient died suddenly while in remission of unknown causes at 6 months post-treatment. Of the two relapses, one patient chose not to receive any obinutuzumab during treatment due to a grade 3 reaction during cycle 1, and both patients initially presented with aggressive leukemic phase disease with Ki67 & gt; 30%. Here we report the pre-planned stage 1 of this phase 2 study, the BOV regimen has resulted in CRs in 8 of the first 9 patients, and accrual continues to stage 2. Expected hematologic and infusional toxicities have been manageable. One patient has discontinued therapy due to toxicity, and the prescribed venetoclax ramp-up has successfully avoided clinically significant tumor lysis syndrome. Accrual continues, and additional follow-up of currently treated patients will provide insights into response duration, OS, and rate of MRD negativity with this regimen. Disclosures Greenwell: Acrotech Biopharma LLC, Kyowa Kirin: Consultancy; Lymphoma Research Foundation: Research Funding. Maddocks:Karyopharm: Consultancy; ADC Therapeutics, AstraZeneca: Consultancy; BMS: Consultancy, Research Funding; Morphosys: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria. Kahl:Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche Laboratories Inc: Consultancy; Pharmacyclics LLC: Consultancy; Genentech: Consultancy; Celgene Corporation: Consultancy; AstraZeneca Pharmaceuticals LP: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy; ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Acerta: Consultancy, Research Funding. Alizadeh:Janssen: Consultancy; Genentech: Consultancy; Pharmacyclics: Consultancy; Chugai: Consultancy; Celgene: Consultancy; Gilead: Consultancy; Roche: Consultancy; Pfizer: Research Funding. Allen:Curio Sciences: Honoraria; Bayer: Consultancy, Other; Clinical Care Options: Speakers Bureau; Research to Practice: Speakers Bureau; Imbrium: Consultancy, Other. Cohen:Genentech, BMS, Novartis, LAM, BioInvent, LRF, ASH, Astra Zeneca, Seattle Genetics: Research Funding; Janssen, Adicet, Astra Zeneca, Genentech, Aptitude Health, Cellectar, Kite/Gilead, Loxo: Consultancy.