Abstract: Introduction: Patients (pts) with limited stage (LS) aggressive large B-cell lymphoma (ALBCL) comprise 30-40% of ALBCLs and are usually treated with R-CHOP with or without consolidative involved field radiation therapy (IFRT). In pts with ALBCL, cytogenetic studies have identified a subset with high-risk disease who harbor MYC rearrangement (MYC-R) with or without BCL2 (BCL2-R) and/or BCL6 (BCL6-R) rearrangements. This has led to the adoption of intensive induction strategies in this population; however, it is unclear if such an approach is necessary in limited stage disease. Methods: We conducted a multi-center (15 US academic centers) retrospective study of MYC-R LS-ALBCL pts with diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL) morphology. LS was defined by stage I and II confined to a single radiation field as determined by the treating center. Pts diagnosed between 1/1/2005 and 3/1/2017 were included. All pts received either R-CHOP or more intensive immuno-chemotherapy (IIC) (i.e. R-DA-EPOCH, R-hyperCVAD/MA, or R-CODOX-M/IVAC) with or without IFRT. Baseline demographic, clinical, laboratory, pathology and outcomes data was collected by retrospective chart review. Stage-modified IPI (sm-IPI) score was calculated [stage II (vs 1), age 〉 60, elevated LDH, and ECOG performance status ≥ 2]. Differences in overall response rate (ORR), complete remission (CR) rate, 2-year progression-free survival (PFS) and overall survival (OS) were compared in pts treated with R-CHOP vs IIC and in pts treated with IFRT vs no IFRT. Results: A total of 142 pts with MYC-R LS-ALBCL were identified, of which 105 fulfilled the inclusion criteria. Baseline characteristics included: median age 65 yrs (range 21-85), 66% male; 14% stage I, 32% stage IE, 28% stage II, 26% stage IIE disease; 17% bulky, 58% extra-nodal, 15% transformed disease, 40% elevated LDH. The majority of pts (70%) had germinal center B-cell phenotype. Eighty-two pts had data on BCL2-R and BCL6-R, of which 41 (50%) had double-hit lymphoma (DHL), including 4 pts with triple-hit lymphoma. Forty-five pts (43%) received R-CHOP, of which 56% had IFRT. Sixty pts (57%) received IIC, of which 42% had IFRT. R-DA-EPOCH was the most common IIC regimen used (85%), followed by R-hyperCVAD/MA (12%). Age (p=0.38), stage (p=0.32), extra-nodal disease (p=0.84), LDH (p=0.09), sm-IPI (p=0.24), morphology (p=0.44) and double-hit status (p=1.00) were similar between pts receiving R-CHOP and IIC. Median no. of cycles (NOC) (6 vs 6) and proportion of pts who received IFRT (56% vs 42%, p=0.17) did not differ in the 2 groups. Median NOC were lower in IFRT vs no IFRT group (4 vs 6; p=0.02). Pts receiving IIC (vs. R-CHOP) were more likely to undergo CNS prophylaxis (CNS-P) (75% vs 29%, p 〈 0.001). No. of pts receiving CNS-P were similar in DHL vs MYC-R only (64% vs 49%; p=0.23). ORR was 90% (83% CR, 7% PR). Pts with DHL were less likely to achieve a CR compared to pts with MYC-R only (73% vs 98%; p=0.011). CR rate was higher in the IFRT vs no-IFRT group (92% vs. 75%, p=0.028). In the 27 pts who had relapsed/refractory disease, distant relapses were more common in the IFRT vs no-IFRT group (87% vs 33%, p=0.007). Median follow-up was 3.2 yrs; 35 (33%) pts progressed or died. Of the 23 deaths, 15 were due to progressive lymphoma, 1 due to treatment-related toxicity and 7 due to unrelated causes. 2-year PFS and OS were 78% and 86% for the entire cohort and 72% and 82% respectively for DHL pts. Sm-IPI ≥ 2 (HR: 2.81, p=0.02) and age ≥ 70 (HR: 4.07, P 〈 0.001) were associated with inferior OS. Stage, extra-nodal disease, morphology, LDH and double hit status did not affect survival. PFS and OS were similar across treatment groups (IFRT vs no IFRT, R-CHOP vs IIC) in the entire cohort (Figures 1 and 2) and in DHL pts (Figures 3 and 4). Use of CNS-P was not associated with improved PFS (HR: 0.57 [95% CI: 023, 1.43]) or OS (HR 0.98 [95% CI: 0.34, 2.85] ). Conclusions: Outcomes of MYC-R LS-ALBCL pts are excellent with 2-year PFS and OS of 78% and 86% respectively. There was no benefit of choosing IIC over R-CHOP or using CNS prophylaxis in pts with MYC-R LS-ALBCL and LS-DHL in our study. While IFRT was effective in inducing CRs and preventing local relapses, distant relapses limited its benefit. Pts with LS-DHL had lower CR rates with similar PFS and OS when compared to those with MYC-R as the sole cytogenetic abnormality. Longer follow up is needed to assess the impact of upfront treatment strategies on late relapses. Disclosures Landsburg: Takeda: Consultancy; Curis: Consultancy, Research Funding. Maddocks:Teva: Honoraria; AstraZeneca: Honoraria; Pharmacyclics/Janssen: Honoraria; Novartis: Research Funding; Pharmacyclics: Research Funding; Merck: Research Funding; BMS: Research Funding. Advani:Bayer Healthcare Pharmaceuticals: Other: Consultancy/Advisory Role; Cell Medica: Other: Consultancy/Advisory Role; Janssen Pharmaceutical: Other: Institutional Research Support; Regeneron Pharmaceuticals, Inc.: Other: Institutional Research Support; Merck: Other: Institutional Research Support; Kyowa: Other: Consulting/Advisory Role; Celgene: Other: Institutional Research Support; Roche/Genentech: Other: Consultancy/Advisory Role, Institutional Research Support; Takeda: Other: Consultancy/Advisory Role; Gilead/Kite: Other: Consultancy/Advisory Role; Autolus: Other: Consultancy/Advisory Role; AstraZeneca: Other: Consultancy/Advisory Role; Seattle Genetics: Other: Consultancy/Advisory role, Institutional Research Support; Bristol Myers Squibb: Other: Consultancy/Advisory role and Institutional Research Support; Forty Seven, Inc: Other: Institutional Research Support; Pharmacyclics: Other: Institutional Research Support; Agensys: Other: Institutional Research Support; Kura: Other: Institutional Research Support; Infinity: Other: Institutional Research Support; Millenium: Other: Institutional Research Support. Barta:Janssen: Membership on an entity's Board of Directors or advisory committees; Merck, Takeda, Celgene, Seattle Genetics, Bayer: Research Funding. Vose:Seattle Genetics, Inc.: Research Funding; Merck Sharp & Dohme Corp.: Research Funding; Novartis: Honoraria, Research Funding; Abbvie: Honoraria; Roche: Honoraria; Epizyme: Honoraria; Kite Pharma: Research Funding; Celgene: Research Funding; Incyte Corp.: Research Funding; Bristol Myers Squibb: Research Funding; Acerta Pharma: Research Funding; Legend Pharmaceuticals: Honoraria. Cohen:Takeda: Research Funding; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; BioInvent: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Infinity Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees. Karmali:AstraZeneca: Speakers Bureau; Gilead: Speakers Bureau. Mehta:Seattle Genetics: Research Funding; Kite: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Research Funding; AstraZeneca: Consultancy, Speakers Bureau; Merck: Research Funding; Spectrum: Consultancy; Epizyme: Research Funding; F. Hoffmann-La Roche Ltd: Research Funding; Incyte: Research Funding; Gilead: Consultancy, Speakers Bureau; Celgene: Consultancy; Carevive: Other: Patient engagement; Medpage: Other: Medical website. Olszewski:Spectrum Pharmaceuticals: Consultancy, Research Funding; TG Therapeutics: Research Funding; Genentech: Research Funding. Hill:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Abstract: Mantle cell lymphoma (MCL) is a B-cell lymphoma characterized by cyclin D1 expression. Autologous hematopoietic cell transplantation (AHCT) consolidation after induction chemotherapy is often used for eligible patients; however, the benefit remains uncertain in the rituximab era. Herein we retrospectively assessed the impact of AHCT consolidation on survival in a large cohort of transplantation-eligible patients age 65 years or younger. PATIENTS AND METHODS We retrospectively studied transplantation-eligible adults age 65 years or younger with newly diagnosed MCL treated between 2000 and 2015. The primary objective was to assess for improved progression-free survival (PFS) with AHCT consolidation and secondarily to assess for improved overall survival (OS). Cox multivariable regression analysis and propensity score–weighted (PSW) analysis were performed. RESULTS Data were collected from 25 medical centers for 1,254 patients; 1,029 met inclusion criteria. Median follow-up for the cohort was 76 months. Median PFS and OS were 62 and 139 months, respectively. On unadjusted analysis, AHCT was associated with improved PFS (75 v 44 months with v without AHCT, respectively; P 〈 .01) and OS (147 v 115 months with v without AHCT, respectively; P 〈 .05). On multivariable regression analysis, AHCT was associated with improved PFS (hazard ratio [HR], 0.54; 95% CI, 0.44 to 0.66; P 〈 .01) and a trend toward improved OS (HR, 0.77; 95% CI, 0.59 to 1.01; P = .06). After PSW analysis, AHCT remained associated with improved PFS (HR, 0.70; 95% CI, 0.59 to 0.84; P 〈 .05) but not improved OS (HR, 0.87; 95% CI, 0.69 to 1.1; P = .2). CONCLUSION In this large cohort of younger, transplantation-eligible patients with MCL, AHCT consolidation after induction was associated with significantly improved PFS but not OS after PSW analysis. Within the limitations of a retrospective analysis, our findings suggest that in younger, fit patients, AHCT consolidation may improve PFS.

Abstract: The impact of MYC translocations (with or without additional BCL 2 or BCL 6 gene rearrangements) on response to salvage therapy and survival in patients with diffuse large B‐cell lymphoma who experience primary treatment failure is not well defined. In this retrospective study, patients with MYC ‐positive DLBCL who fail on primary treatment have response rates similar to those observed after salvage therapy compared with their MYC ‐negative counterparts, but their survival is dismal irrespective of additional “hits” and hematopoietic cell transplantation, representing an unmet medical need.

Abstract: The B-cell receptor signaling pathway is active in diffuse large B-cell lymphomas, with increased expression of MYC and BCL2 protein. The overall response rate was 60% for relapsed/refractory non–germinal center double-expressor lymphoma patients treated with ibrutinib.

Abstract: In this real-world evaluation of tafasitamab-lenalidomide (TL) in relapsed/refractory LBCL, patients receiving TL had higher rates of comorbidities and high-risk disease characteristics, and substantially lower progression-free survival and overall survival, compared to the L-MIND registration clinical trial for TL.

Abstract: 7541 Background: Translocations involving MYC are a hallmark of poor prognosis among patients with newly diagnosed DLBCL. The impact of MYC translocations with or without additional “hits” involving BCL2 or BCL6 in response to salvage therapy and survival in R/R DLCBL is not well defined. Methods: We performed a multicenter retrospective study of 176 patients with R/R DLBCL failing to achieve CR or relapsing within 6 months after completion of upfront chemoimmunotherapy and for whom FISH information on MYC, BCL2 and BCL6 was available. The objectives were to examine the response to salvage therapy, utilization of hematopoietic cell transplantation (HCT) and survival outcomes in MYC- (n = 120), MYC+ single hit (SH, n = 28), and MYC+ double hit (DH, n = 36) R/R DLBCL. Results: Overall response rate to first salvage therapy and utilization of HCT was comparable between the 3 cohorts (Table). 2-year OS was 0% in MYC+ SH, 8.8% in MYC+ DH and 29.9% in MYC- cases (p = 0.001) without difference in OS between SH and DH (P = 0.8). The higher risk of death for MYC+ SH (HR 1.79, 95% C.I. 1.03-3.11, P = 0.03) and MYC+ DH (HR 1.93, 95% C.I. 1.23-3.00, P = 0.004) persisted after adjustment for covariates. For patients who underwent auto-HCT, 2-year OS was 0% in MYC+ SH, 29.3% in MYC+ DH and 55.4% in MYC- cases (p 〈 0.001) without significant difference between SH and DH (P = 0.8). All 4 MYC+patients who underwent allo-HCT relapsed in 〈 4 months. Conclusions: MYC+ R/R DLBCL have similar response to salvage therapy than the MYC- counterparts but dismal survival irrespective of additional “hits” and even if HCT can be performed. MYC+ R/R DLBCL represents an unmet medical need and should be prioritized for clinical trials with novel agents and innovative cellular therapies. [Table: see text]

Abstract: Introduction: Preclinical data have suggested that B-cell receptor-associated genes are upregulated in diffuse large B cell lymphoma (DLBCL) with increased expression of MYC protein, as well as MYC and BCL2 protein, also known as "double expressor" lymphoma (DEL) (Am J Surg Pathol. 2017 Apr;41(4):541-549 and PLoS One. 2017 Feb 17;12(2):e0172364). Patients (pts) with DEL respond poorly to cytotoxic chemotherapy; thus novel treatment approaches are needed for this disease. Here, we report outcomes of pts with relapsed/refractory (R/R) DLBCL and high grade B cell lymphoma (HGBL) treated with ibrutinib (ibr) monotherapy. Methods: Pts analyzed were those with R/R DLBCL or HGBL treated with ibr monotherapy at University of Pennsylvania, Ohio State University or Cleveland Clinic with immunohistochemical (IHC) stains for MYC and BCL2 from the tissue specimen obtained most recently prior to initiation of ibr available for hematopatholoigst (HP) review, and determined to have IHC scores of ≥40% for MYC and ≥50% for BCL2, meeting criteria for definition of DEL. Exclusion criteria were HIV positivity, post-transplant lymphoproliferative disorder, prior chronic lymphocytic leukemia and inadequate data. All available IHC stains for MYC and BCL2 were scored as positive or negative as per the aforementioned cutoffs by a HP at the treating center (HP1) as well as a second HP at one of the other centers (HP2) through review of digital slide images. In cases of disagreement, the score assigned in the clinical pathology report (CPR) was used as a tiebreaker. Progression free survival (PFS) was defined as the interval between time of initiation of ibr and documented disease progression, change in therapy (tx) if no disease response or last follow-up in remission, and overall survival (OS) between time of initiation of ibr and death or last follow-up while alive. Data were censored on 7/1/18. Results: Twenty-five cases with IHC stains for MYC and BCL2 were reviewed, with 19 meeting criteria for DEL which were included in the analysis. Clinicopathologic characteristics at time of ibr initiation were median age 69 years, 32% female, 63% stage III-IV, 74% elevated LDH, 11% bone marrow (BM) involvement, 11% B symptoms present, 21% extranodal (EN) disease at 〉 1 site, 32% ECOG performance status (PS) 〉 1, 58% with International Prognostic Index score (IPI)≥3, 26% HGBL, median Ki67 80% and 21% germinal center (GCB) cell of origin (COO) by Hans algorithm. Of pts with available fluorescence in situ hybridization (FISH) data, 50% (7/14), 25% (3/12) and 14% (1/7) demonstrated MYC, BCL2 and BCL6 rearrangements, respectively, and 3 pts were known to be double hit lymphoma. First-line tx was R-EPOCH in 26% and R-CHOP in 74%. Autologous stem cell transplantation was received by 42% prior to treatment with ibr. The proportion of pts receiving ibr as 2nd, 3rd, 4th and ≥5th line of tx was 21%, 37%, 21% and 21%, respectively. The time from initiation of the prior line of tx to initiation of ibr was 〈 6 months (mo), 6-12 mo and 〉 12 mo in 79%, 16% and 5%, respectively. Overall response to ibr was 47% (37% complete response and 10% partial response) and 5% with stable disease. All responses were seen in pts with non-GCB COO. The median PFS was 4.7 mo, median OS 5.5 mo and median duration of response 4.2 mo. For all cases reviewed (n=25), MYC IHC was scored by HP1 and HP2 and available in the CPR in 100%, 84% and 88%, respectively, and BCL2 IHC in 100%, 84% and 100%, respectively. Rates of concordance and kappa (κ) coefficient were as follows: HP1 and HP2 for MYC 85.7% (κ=0.49), BCL2 95.2% (κ=0.64) and DEL 84.0% (κ=0.61); HP1 and CPR for MYC 86.3% (κ=0.70), BCL2 96.0% (κ=0.78) and DEL 81.8% (κ=0.62); HP2 and CPR for MYC 66.7% (κ=0.18), BCL2 90.5% (κ=0.45) and DEL 68.2% (κ=0.34). In 4 cases with disagreement between HP1 and HP2 regarding DEL status, the CPR agreed with HP1, and 4 cases were identified as DEL by both HP1 and HP2 but not by CPR. Conclusion: An objective response to ibr was experienced by nearly half of pts with R/R DEL as defined by multicenter HP review in this series. Our data suggest a potential benefit to the use of ibr monotherapy as bridging tx to curative-intent cellular tx, as well as support the incorporation of ibr into clinical trials for the R/R DEL pt population. A relatively high rate of concordance between HP1 and CPR in identifying cases of DEL suggests that local review of MYC and BCL2 IHC may be a reasonable alternative for determining DEL status when central review is infeasible. Disclosures Landsburg: Curis, INC: Consultancy, Research Funding; Takeda: Research Funding. Maddocks:Novartis: Research Funding; Pharmacyclics/Janssen: Honoraria; BMS: Research Funding; Merck: Research Funding; Pharmacyclics: Research Funding; AstraZeneca: Honoraria; Teva: Honoraria. Hill:Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees. Dwivedy Nasta:Incyte: Research Funding; Merck: Other: DSMC; Pharmacyclics: Research Funding; Aileron: Research Funding; Roche: Research Funding; Takeda/Millenium: Research Funding; Rafael/WF: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Debiopharm: Research Funding. Svoboda:Regeneron: Research Funding; TG Therapeutics: Research Funding; Seattle Genetics: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Merck: Research Funding; Pharmacyclics: Consultancy, Research Funding; KITE: Consultancy; Kyowa: Consultancy. Schuster:Physician's Education Source, LLC: Honoraria; Dava Oncology: Consultancy, Honoraria; Merck: Consultancy, Honoraria, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; OncLive: Honoraria; Genentech: Honoraria, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals Corporation: 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; Nordic Nanovector: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

Abstract: Background: Plasmablastic lymphoma (PBL) is a rare subtype of Non-Hodgkin Lymphoma with a well-known association with HIV infection. The outcomes of PBL patients are typically described with high relapse rates and poor prognosis. (Loghavi S, J Hematol Oncol. 2015; Morscio J, Am J of Pathol. 2014; Castillo JJ, Clin Lymphoma Myeloma Leuk. 2011; Castillo JJ, Am J Hematol. 2008) There has been a paucity of data suggesting that limited stage disease (Ann Arbor stage I-II) may have a more favorable prognosis. However, due to the rarity of this disease there have been no large-scale reviews to confirm this. Thus, many patients with limited stage disease are subject to the aggressive therapy recommendations based on the poor outcomes of PBL patients as a whole. (Loghavi S, J Hematol Oncol. 2015; NCCN Guidelines, version 2.2020; Al-Malki MM, BBMT. 2014) We attempted to determine the treatment patterns and outcomes of patients with limited stage PBL. Methods: We conducted a multi-center (13 US academic centers) retrospective study of patients with limited stage (Ann Arbor stage I-II) Plasmablastic lymphoma. Determination of limited stage and diagnosis of PBL was determined by the investigators at each individual center. Patients diagnosed between 1/1/1990 and 6/1/2018 were included. Baseline demographic, clinical, laboratory, pathology, and outcomes data were extracted by retrospective chart review. Kaplan Meier was utilized for time to event analysis. Results: Baseline characteristics are included in table 1. A total of 80 patients were identified with limited stage disease. With a median follow up of 34 months the 3-yr Progression free survival (PFS) and overall survival (OS) was 71.9% and 78.7% respectively (Figure 1A and 1B). Patients that received frontline chemotherapy with (n=29) and without RT (n=36) had a 3-yr PFS and OS of 84.6% and 96.2% as compared to 64.5% and 70.8%, respectively (Figure 2A and 2B; Figure 3A and 3B). The Hazard ratio (HR) for PFS and OS for chemo (reference) vs chemo-RT was 0.47 (95% CI 0.18-1.3; P=0.131) and 0.18 (95% CI 0.04-0.84; p=0.029) respectively. The HR for PFS and OS for CHOP (n=14, reference) vs EPOCH (n=33) based regimens was 0.37 (95% CI 0.11-1.2; p=0.106) and 0.36 (95% CI 0.079-1.6; p=0.182) respectively. Patients with stage I/IE disease (n=56) had a 3-yr PFS and OS of 73.1% and 81.2% respectively. Patients with stage II/IIE disease (n=24) had a 3-yr PFS and OS of 69.3% and 73.4% respectively. Patients that received aggressive treatment (n=17) with Hyper-CVAD based regimens and/or Auto-SCT as consolidation had a 3-yr PFS and OS of 63.6% and 72.7% respectively. Patients with concomitant HIV (n=16) had a 3-yr PFS and OS of 80.8% and 77.4% respectively. Seven patients received RT alone and 6 patients had surgical resection alone as frontline therapy; 1 patient received no therapy; 1 patient received HAART therapy only and remains in CR without any other treatment for PBL 29 months after diagnosis. There were 8 deaths (10%) related to PBL, 3 deaths (4%) related to treatment of PBL (2 during frontline chemo and 1 upon relapse with salvage chemo), and 9 deaths (11%) related to other causes. The 3-yr lymphoma free survival (LFS) of the entire cohort, pts receiving chemo alone, and pts receiving chemo-RT (without including treatment related mortality (TRM) as an event) was 89.1%, 85.2%, and 100% respectively. The 3-yr LFS survival of the entire cohort, pts receiving chemo alone, and pts receiving chemo-RT (including TRM as an event) was 85.1%, 80.0%, and 96.2% respectively. Discussion: Here we report the largest review to our knowledge of limited stage PBL. Outcomes appear to be excellent with 3-yr PFS and OS of 71.9% and 78.7% respectively and a 3-yr LFS of 89.1% (85.1% when attributing TRM as an event). There was no obvious benefit to receiving aggressive therapy with H-CVAD based regimens and/or Auto-SCT. Although this is a small, uncontrolled sample size the HR for OS was improved in patients receiving frontline chemo-RT vs chemo alone 0.18 (95% CI 0.04-0.84; p=0.029). However, this did not take into account TRM with or progression while receiving frontline chemotherapy. Patients who were HIV+ had similar PFS and OS outcomes compared to the entire cohort. This retrospective study clearly demonstrates the favorable outcomes in this patient population, especially in those able to receive definitive therapy for their disease. Disclosures Hess: ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS, AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Patel:Takeda: Consultancy, Research Funding; Precision Biosciences: Research Funding; Nektar: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Poseida: Research Funding; Cellectis: Research Funding; Oncopeptides: Consultancy; Janssen: Consultancy, Research Funding. Nowakowski:Nanostrings: Research Funding; Seattle Genetics: Consultancy; Curis: Consultancy; Ryvu: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other; Kymera: Consultancy; Denovo: Consultancy; Kite: Consultancy; Celgene/BMS: Consultancy, Research Funding; Roche: Consultancy, Research Funding; MorphoSys: Consultancy, Research Funding. Chavez:Bayer: Consultancy; AbbVie: Consultancy; BeiGene: Speakers Bureau; Morphosys: Consultancy, Speakers Bureau; Merck: Research Funding; AstraZeneca: Speakers Bureau; Celgene: Consultancy; Genentech: Speakers Bureau; Epizyme: Speakers Bureau; Gilead: Consultancy; Novartis: Consultancy; Kite, a Gilead Company: Consultancy, Speakers Bureau; Karyopharm: Consultancy; Verastem: Consultancy; Pfizer: Consultancy. Hill:Beigene: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Honoraria, Research Funding; Takeda: Research Funding; AstraZenica: Consultancy, Honoraria, Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding. Maddocks:Pharmacyclics: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Karyopharm: Consultancy; ADC Therapeutics, AstraZeneca: Consultancy; BMS: Consultancy, Research Funding. Wagner-Johnston:ADC Therapeutics, Regeneron, CALIB-R, Verastem: Membership on an entity's Board of Directors or advisory committees. Kahl:AstraZeneca Pharmaceuticals LP: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy; Pharmacyclics LLC: Consultancy; Genentech: Consultancy; Acerta: Consultancy, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Consultancy; ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche Laboratories Inc: Consultancy. Alderuccio:ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Forma Therapeutics: Other: Family member; Agios Pharmaceuticals: Other: Family member; Oncinfo: Honoraria; Inovio Pharmaceuticals: Other: Family member; Foundation Medicine: Other: Family member; Puma Biotechnology: Other: Family member; OncLive: Honoraria. Lossos:Janssen Biotech: Honoraria; Verastem: Consultancy, Honoraria; Janssen Scientific: Consultancy, Other; Seattle Genetics: Consultancy, Other; Stanford University: Patents & Royalties; NCI: Research Funding. Portell:Bayer: Consultancy; BeiGene: Consultancy, Research Funding; Kite: Consultancy, Research Funding; Acerta/AstraZeneca: Research Funding; Amgen: Consultancy; Janssen: Consultancy; Pharmacyclics: Consultancy; AbbVie: Research Funding; TG Therapeutics: Research Funding; Infinity: Research Funding; Roche/Genentech: Consultancy, Research Funding; Xencor: Research Funding. Landsburg:Celgene: Membership on an entity's Board of Directors or advisory committees; Triphase: Research Funding; Takeda: Research Funding; Curis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Morphosys: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Speakers Bureau. Castillo:TG Therapeutics: Research Funding; Beigene: Consultancy, Research Funding; Kymera: Consultancy; Janssen: Consultancy, Research Funding; Abbvie: Research Funding; Pharmacyclics: Consultancy, Research Funding.

Abstract: Introduction: Modern chemoimmunotherapy cures the majority of patients (pts) with newly diagnosed diffuse large B cell lymphomas (DLBCL). The paradigm for pts who relapse has been salvage chemotherapy followed by autologous hematopoietic cell transplantation (auto-HCT) when chemosensitive disease. This approach is often also applied to pts with primary treatment failure (PTF), although this group is heterogeneous and outcomes of HCT in this population have not been well described. Methods: Fifteen US academic medical centers contributed pts to the REgistry of diFfuse large B cell lymphoma with prImary treatmeNt failurE (REFINE) collaboration. REFINE retrospectively captured patient, disease and treatment characteristics and response as assessed by treating center. Eligible pts were ≥ 18 years diagnosed with DLBCL during 2008-2015, who received upfront therapy including anthracycline and CD20-directed antibody and developed one of 3 patterns of PTF: relapse 〈 6 months following CR (early relapse- ER); only partial remission (PR) or stable disease (SD) with upfront therapy (residual disease-RD); progressive disease (PD) while receiving upfront therapy (primary progression-PP). Pts with HIV infection, primary CNS lymphoma or lymphoma transforming from a more indolent histology were excluded. Results: Among 331 cases included in REFINE, patterns of PTF were ER in 95 (28.7%), RD in 92 (27.8%) and PP in 144 (43.5%) pts. Salvage therapy was administered to 94.6% of pts. We analyzed the 157 (47.4%) PTF pts who subsequently underwent HCT, 132 auto-HCT and 33 allo-HCT (8 after failure of auto-HCT) (Table). Nearly half of pts were in CR at transplant, after 1-2 lines of salvage therapy. Among all pts receiving auto-HCT, 2-year progression-free survival (PFS) from time of transplant was 38.4% (95% C.I. 29.6-47.2%) and overall survival (OS) 54.9% (95% C.I. 44.9-64.9%). Two-year OS from auto-HCT was affected by pattern of PTF: 71.3% for ER, 55.0% for RD and 41.7% for PP (P=0.05). OS at 2-years was 23.7% for auto-HCT pts with germinal center B (GCB)type,c-myc(+) (by FISH) tumors vs. 66.7% for GCB, c-myc (-), vs. 67.8% for non-germinal center (NGC) (P=0.01). Auto-HCT pts with intermediate-high/high NCCN-IPI at time of PTF had 2-year OS of 28.6% vs. 66.0% for intermediate-low and 80.9% for low risk (P 〈 0.001). In multivariate analysis, PP pattern, c-myc(+) status and intermediate-high/high NCCN-IPI at time of PTF, hereforth called ultra-high-risk (UHR) fetures, negatively affected survival. Auto-HCT pts with no UHR features had 2-year OS of 74.3%(95% C.I. 60.0-88.6%)vs. 59.6% (95% C.I. 44.5-74.7%)for pts with 1 vs. 10.7% (95% C.I. 0-24.4%)for pts with 2-3 features (Figure, P 〈 0.001). Among pts who underwent allo- HCT, 2-year PFS and OS were 20.5% (95% C.I. 6.4-34.6%)and 32.7% (95% C.I. 13.1-52.3%)respectively. Failure of allo-HCT was primarily due to disease progression, with only one death occuing due to HCT complications. Conclusions: Pts with DLBCL experiencing PTF and 2 or more UHF features have dismal outcome after auto-HCT and should be targeted for experimental modalities of cellular therapy. Outcomes of allo-HCT in DLBCL with PTF are poor, due to rapid and fatal relapses. Table. Table. Figure. Figure. Disclosures Costa: Sanofi: Honoraria, Research Funding. Reddy:INFINITY: Membership on an entity's Board of Directors or advisory committees; KITE: Membership on an entity's Board of Directors or advisory committees; celgene: Membership on an entity's Board of Directors or advisory committees; GILEAD: Membership on an entity's Board of Directors or advisory committees. Karmali:Celgene: Speakers Bureau. Chavez:Janssen: Speakers Bureau. Calzada:Seattle Genetics: Research Funding. Barta:Janssen: Honoraria, Speakers Bureau; Celgene, Merck, Seattle Genetics: Research Funding. Flowers:Pharmacyclics, LLC, an AbbVie Company: Research Funding; Mayo Clinic: Research Funding; Acerta: Research Funding; Roche: Consultancy, Research Funding; TG Therapeutics: Research Funding; ECOG: Research Funding; Genentech: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; NIH: Research Funding; Infinity: Research Funding; Millenium/Takeda: Research Funding; AbbVie: Research Funding. Fenske:Seatle Genetics: Honoraria; Pharmacyclics: Honoraria; Celgene: Honoraria; Millennium/Takeda: Research Funding. Cohen:Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium/Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Infinity: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Research Funding. Hamadani:Takeda: Research Funding.