ALBERT

Description: Background Mantle cell lymphoma (MCL) is an incurable B-cell non-Hodgkin lymphoma associated with poor outcomes. First-line treatment incorporates cytotoxic chemotherapy and rituximab, but there is no single standard of care regimen. In British Columbia (BC), between January 2003 and May 2013, R-CHOP was the preferred induction regimen. Based on results from the STIL-1 trial (Rummel et al, Lancet 2013) demonstrating improved CR rate and prolonged progression-free survival (PFS) of bendamustine and rituximab (BR) compared with R-CHOP, in June 2013, BR became the standard first-line therapy for all patients with MCL regardless of age. In both eras, fit patients generally ≤65 years of age responding to induction were eligible for high-dose BEAM and autologous stem cell transplantation (ASCT). Maintenance rituximab (MR) has been offered to responding patients post ASCT since 2004 and for transplant ineligible patients since 2012. The aim of this study was to assess the efficacy of BR as an induction regimen for MCL. Methods Patients with MCL treated with first-line BR were identified in the BC Cancer clinical and pathology databases as well as the Leukemia/BMT Program of BC transplant database. BR was initiated no later than December 2018. Treatment received was verified using the BC Cancer Provincial Pharmacy database, and clinical characteristics were verified using the BC Cancer Information System. Radiotherapy for localized disease, splenectomy, or a period of observation prior to systemic therapy were permitted. PFS and overall survival (OS) were calculated from the date of initiation of systemic therapy. In the subgroup of patients ≤65 years of age, results were compared to a historical cohort uniformly treated with R-CHOP. Baseline and treatment characteristics associated with PFS or OS (p65 years old, 9 underwent ASCT (age 66-71) and 92 did not. 63/69 patients received MR after ASCT, and 77/121 received MR after BR (without ASCT). Reasons for not receiving MR (6 after ASCT, 44 after BR) were 25 PD, 10 ASCT/BR toxicity, 7 pending, 3 patient preference, 3 early deaths, 2 physician preference. With a median follow-up of 2.4y (range 0.2 - 6.1) in living patients the 3y OS was 69.5% (95% CI 69.4-70.6) and 3y PFS 62.8% (95% CI 62.4-63.6). Baseline characteristics and outcomes were similar between patients ≤65y treated with BR vs. R-CHOP (Table 1, Figure 1A and 1B). 81/140 (58%) patients treated with R-CHOP underwent ASCT. In the subgroup of patients who underwent ASCT, outcomes calculated from the point of ASCT were not statistically different between BR vs. R-CHOP. In univariate analysis, age 〉65y, ECOG performance status 〉1, elevated LDH, blastoid/pleomorphic morphology, no ASCT, and no MR were associated with worse PFS and OS. In multivariate analysis including these variables as well as chemoimmunotherapy regimen, treatment with BR was not associated with PFS or OS. Conclusions In this population-based analysis, BR is an effective induction regimen for both transplant eligible and ineligible patients. ASCT is feasible in patients treated with BR induction. Even though BR was associated with a numerical improvement in PFS compared to R-CHOP in patients ≤65y, differences in PFS and OS were not statistically significant. Longer follow-up is necessary to fully understand the impact of BR in the frontline setting. We observed PD in 12% patients, suggesting that BR may not be an optimal induction regimen across all patients with MCL, particularly in those with aggressive or highly proliferative disease. Disclosures Villa: Roche, Abbvie, Celgene, Seattle Genetics, Lundbeck, AstraZeneca, Nanostring, Janssen, Gilead: Consultancy, Honoraria. Sehn:Morphosys: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria; Merck: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Acerta: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria; Apobiologix: Consultancy, Honoraria; Janssen-Ortho: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria; F. Hoffmann-La Roche/Genentech: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Verastem: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Acerta: Consultancy, Honoraria; F. Hoffmann-La Roche/Genentech: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; TEVA Pharmaceuticals Industries: Consultancy, Honoraria; TEVA Pharmaceuticals Industries: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Janssen-Ortho: Honoraria; Celgene: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria. Savage:BMS, Merck, Novartis, Verastem, Abbvie, Servier, and Seattle Genetics: Consultancy, Honoraria; Seattle Genetics, Inc.: Consultancy, Honoraria, Research Funding. Song:Celgene: Honoraria, Research Funding; Janssen: Honoraria; Takeda: Honoraria; Amgen: Honoraria. Freeman:Seattle Genetics, Janssen, Amgen, Celgene, Abbvie: Consultancy, Honoraria. Scott:Roche/Genentech: Research Funding; Celgene: Consultancy; Janssen: Consultancy, Research Funding; NanoString: Patents & Royalties: Named inventor on a patent licensed to NanoSting [Institution], Research Funding. Gerrie:Lundbeck, Seattle Genetics: Consultancy, Honoraria.

Description: Cure rates for primary mediastinal large B-cell lymphoma (PMBCL) have improved with the integration of rituximab. However, the type of primary therapy and role of radiotherapy (RT) remains ill-defined. Herein, we evaluated the outcome of PMBCL primarily treated with R-CHOP and the impact of an end-of-treatment (EOT) FDG-PET scan to guide consolidative RT. Patients ≥18 years of age with PMBCL treated with curative intent R-chemotherapy were identified. Prior to 2005, patients were recommended to receive R-CHOP +RT (RT era). Beginning in 2005, EOT PET was used to guide RT and only those with a PET-positive scan received RT (PET era). In total, 159 patients were identified, 94% were treated with R-CHOP and 44% received RT - 78% in RT era, 28% in PET era. The 5-year time to progression (TTP) and OS for the entire cohort were 80% and 89%, respectively, similar across treatment eras. Overall, 10% had refractory disease. In total, 113 patients had an EOT PET scan: 63% negative and 37% positive with a 5-year TTP of 90% vs 71% and 5-year OS of 97% vs 88%, respectively. For those with Deauville (D) scored PET scans (n=103), the 5-year TTP for PET-negative cases by Deauville criteria (D1-D3,DX) was 91%, with inferior outcomes for D5 vs D4 (5-year TTP 33% vs 87%, p=0.0002). Outcomes for R-CHOP treated PMBCL patients treated with R-CHOP are favorable and use of a PET-adapted approach reduces RT in the majority of patients. A small proportion have refractory disease and may benefit from an alternate treatment.

Description: Introduction: Limited stage nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a highly curable malignancy with an excellent prognosis. Given disease rarity, there are few prospective studies and as a result, diverse treatment approaches are used in both the adult and pediatric populations. At BC Cancer, provincial treatment guidelines for limited stage NLPHL have largely followed that of classical HL: Prior to 2005, radiotherapy (RT) was integrated usually as combined modality therapy (CMT); after 2005, an adaptive approach using 18F-fluoro-2-deoxyglucose positron emission tomography (PET) was adopted. Herein, we evaluated the impact of using this approach. Methods: Adult (〉16 years [y]) patients (pts) diagnosed with limited stage NLPHL (stage 1A, 1B or 2A, non-bulky [0.1) or by stage (1 vs 2) (p=0.93). Overall, there have been 7 lymphoma recurrences (CMT era n=3, PET era n=4), including 3 (3%) with transformed disease (biopsy proven T cell rich B cell lymphoma n=1, presumed aggressive lymphomas based on new splenic nodules n=2). In total, there were 48/52 cases that had a PET2 scan interpreted using the D criteria, including 30 in the IHP time period that were re-reviewed: 85% were PETneg (n=41); 15% were PETpos (n=7). Four CHT treated pts did not receive a PET2 scan: RT added (CHT toxicity) n=3; death (diabetic ketoacidosis [DKA] post cycle 1 ABVD) n=1. All PETpos cases and only 4 PETneg cases (CHT toxicity n=2, PETpos by IHP criteria n=2) received RT. Considering PET-specific outcomes, the 5 y PFS and TTP were both 92% for PETneg and 80% for PETpos cases (p=0.56) (Figure 1). Three recurrences occurred in PETneg pts (DX n=1, D2 n=2), all of which had received ABVD alone but only 1 would have been solely in a RT field. The single recurrence among the PETpos cases (D5) was outside of the RT field. In the whole cohort, 9 pts have died (CMT era n=5, PET era n=4). Two deaths in the PET era were deemed related to NLPHL: 1 patient refused primary therapy and died of progressive disease and the other died during ABVD of DKA, possibly treatment related. The remaining deaths were due to other malignancies (lung n=2 [one within RT field], vulvar n=1, anaplastic large cell lymphoma n=1) or unknown causes (n=3). Conclusions: Consistent with other modern series, the outcome of pts with limited stage NLPHL is excellent with both 5 y PFS and OS exceeding 90%. Pts with an interim PETneg scan have a favorable outcome although longer follow-up is needed given the long natural history of NLPHL. This represents the largest experience of a PET-adapted approach in NLPHL and supports that ABVD alone is a viable option in selected patients with consideration of both acute and long term toxicities. Disclosures Villa: Roche, Abbvie, Celgene, Seattle Genetics, Lundbeck, AstraZeneca, Nanostring, Janssen, Gilead: Consultancy, Honoraria. Scott:Celgene: Consultancy; Janssen: Consultancy, Research Funding; Roche/Genentech: Research Funding; NanoString: Patents & Royalties: Named inventor on a patent licensed to NanoSting [Institution], Research Funding. Gerrie:Lundbeck, Seattle Genetics: Consultancy, Honoraria. Freeman:Seattle Genetics, Janssen, Amgen, Celgene, Abbvie: Consultancy, Honoraria. Pickles:TarSera: Honoraria, Other: Participated in advisory board meeting; Astellas Inc.: Research Funding; Abbvie, Sanofi: Consultancy, Honoraria. Sehn:Morphosys: Consultancy, Honoraria; TEVA Pharmaceuticals Industries: Consultancy, Honoraria; F. Hoffmann-La Roche/Genentech: Consultancy, Honoraria, Research Funding; F. Hoffmann-La Roche/Genentech: Consultancy, Honoraria, Research Funding; Astra Zeneca: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Acerta: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria; TEVA Pharmaceuticals Industries: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria; Acerta: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria; Apobiologix: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria; Janssen-Ortho: Honoraria; Janssen-Ortho: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Verastem: Consultancy, Honoraria. Connors:Takeda Pharmaceuticals: Honoraria; Seattle Genetics: Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy. Savage:BMS, Merck, Novartis, Verastem, Abbvie, Servier, and Seattle Genetics: Consultancy, Honoraria; Seattle Genetics, Inc.: Consultancy, Honoraria, Research Funding.

Description: Background: Treatment practices for patients with limited-stage DLBCL are varied and include combined-modality treatment (3 cycles immunochemotherapy + radiation therapy) or immunochemotherapy alone. Since 2005, patients (pts) in BC with limited-stage DLBCL (stage I/II, no B-symptoms, mass 〈 10cm) have been treated according to a PET-guided algorithm. Following 3 cycles of R-CHOP, pts undergo FDG-PET/CT scan; PET-negative pts receive one additional cycle of R-CHOP, while PET-positive pts receive involved-site radiation therapy (RT). We present long-term follow-up of this population-based experience. Methods: Using the BC Cancer Lymphoid Cancer Database we identified all pts who were diagnosed with limited-stage DLBCL from Mar 2005 to February 2019 and underwent a PET/CT after 3 cycles of curative-intent R-CHOP, in keeping with the PET-guided policy. Pts with primary CNS, primary testicular, PMBCL, PTLD, and transformed/discordant/composite lymphoma were excluded. Pts with evidence of progressive disease prior to or on mid-treatment PET/CT were also excluded. All PET/CT scans were performed and reviewed centrally. Prior to 2014, interpretation was based on the International Harmonization Project (IHP) criteria, and subsequently according to Deauville criteria. Importantly, uptake greater than the mediastinal blood pool was consistently used to determine PET-positivity (ie. PET-positive by IHP, or D3-5 by Deauville). Results: Clinical characteristics of the 319 pts identified are as follows: median age, 68 y (range 19-92); 48%, male; 59%, stage I; 41%, stage II; 8%, PS〉1; 13%, elevated LDH; 52%, at least 1 extranodal site; 37%, mass size ≥ 5cm. Stage-modified IPI risk score: 19%, 0; 45%, 1; 27%, 2; 9%, 3-4. Median follow-up is 6.25 yrs (range 0.42-14.25). After 3 cycles of R-CHOP: 254 pts (80%) were PET-negative; 59 pts (18%) were PET-positive; and 6 pts (2%) were considered PET-indeterminate (by IHP). Elevated serum LDH (p4 years from diagnosis. Of the 6 PET-indeterminate patients, 2 received RT and 3/6 have relapsed. Overall 5-year time-to-progression (TTP) censoring deaths from unrelated causes is 89% (92% for PET-negative and 80% for PET-positive pts). Overall 5-year PFS is 84% (88% for PET-negative and 74% for PET-positive pts) and 5-year OS is 87% (90% for PET-negative and 77% for PET-positive pts). On univariate analysis, age〉60, PS〉1, stage-modified IPI, and PET status were significant predictors of TTP. On multivariate analysis controlling for age〉60, stage, PS, LDH, presence of extranodal involvement, mass size ≥ 5cm, and PET status, only age (p=0.002) and PET status (p=0.004) remained independent predictors of TTP. Conclusion: Using a PET-guided approach to treatment, the majority of patients with limited-stage DLBCL have negative PET scans after 3 cycles of R-CHOP. Patients with negative PET scans have an excellent outcome when treated with 4 cycles of R-CHOP alone, without exposure to radiation. Patients with a positive PET scan who complete treatment with radiation therapy have a slightly less favorable outcome, and may be appropriate for alternative approaches. A detailed analysis of patterns of relapse, as well as efforts to identify clinical factors, PET parameters and biomarkers associated with poor outcome and delayed relapse are ongoing. Figure Disclosures Sehn: Acerta: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; TEVA Pharmaceuticals Industries: Consultancy, Honoraria; F. Hoffmann-La Roche/Genentech: Consultancy, Honoraria, Research Funding; TG Therapeutics: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria; TEVA Pharmaceuticals Industries: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria; Janssen-Ortho: Honoraria; Janssen-Ortho: Honoraria; Merck: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; F. Hoffmann-La Roche/Genentech: Consultancy, Honoraria, Research Funding; Acerta: Consultancy, Honoraria. Scott:NanoString: Patents & Royalties: Named inventor on a patent licensed to NanoSting [Institution], Research Funding; Roche/Genentech: Research Funding; Janssen: Consultancy, Research Funding; Celgene: Consultancy. Gerrie:Lundbeck, Seattle Genetics: Consultancy, Honoraria. Freeman:Seattle Genetics, Janssen, Amgen, Celgene, Abbvie: Consultancy, Honoraria. Pickles:TarSera: Honoraria, Other: Participated in advisory board meeting; Abbvie, Sanofi: Consultancy, Honoraria; Astellas Inc.: Research Funding. Savage:Seattle Genetics, Inc.: Consultancy, Honoraria, Research Funding; BMS, Merck, Novartis, Verastem, Abbvie, Servier, and Seattle Genetics: Consultancy, Honoraria.

Description: When the WHO defined high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (HGBL-DH/TH) as a clinical category, rearrangements were the only structural variant (SV) incorporated. An "atypical double-hit" entity has been proposed, encompassing tumors with concurrent MYC and BCL2 SVs other than co-occurring translocations - i.e. copy number variations (CNVs). While the identification of a gene expression signature (DHITsig) shared among tumors harboring MYC and BCL2 rearrangements (HGBL-DH/TH-BCL2) has confirmed a shared underlying biology, the biological implication of MYC and BCL2 CNVs requires further elucidation. We performed a comprehensive analysis of MYC and BCL2 SVs, as determined by fluorescent in situ hybridization (FISH), in a cohort of 802 de novo tumors with diffuse large B-cell lymphoma (DLBCL) morphology. While BCL2 CNVs were associated with increased expression, MYC CNVs were not. Furthermore, MYC and BCL2 CNVs, in the context of atypical double-hit, did not confer a similar gene expression profile as HGBL-DH/TH-BCL2. Finally, while MYC IHC has been proposed as a screening tool for FISH testing, two mechanisms were observed that uncoupled MYC rearrangement from IHC positivity. 1) low MYC mRNA expression and 2) false-negative immunohistochemistry (IHC) staining mediated by a single nucleotide polymorphism resulting in an asparagine to serine substitution at the 11th amino acid residue of MYC (MYC-N11S). Taken together, these results support the current exclusion of MYC and BCL2 CNVs from HGBL-DH/TH and highlight the ability of a molecular based classification system to identify tumors with shared biology that FISH and IHC fail to fully capture.

Description: Consolidative radiation therapy (RT) for advanced-stage diffuse large B-cell lymphoma (DLBCL) remains controversial with routine practice continuing to include RT in patients with initial bulky disease or residual masses. PET-CT is a sensitive modality for detecting the presence of residual disease at end-of-treatment (EOT). A PET-guided approach to selectively administer RT has been policy in BC since 2005. Patients with advanced-stage DLBCL diagnosed between January 2005 - March 2017 treated with at least 6 cycles of R-CHOP that underwent EOT-PET were included in this analysis. Those with complete metabolic response (PET-NEG) were observed; those with PET-positive scans (PET-POS) were offered consolidative RT, when feasible. 723 patients were identified with median follow-up of 4.3 years: 517 (72%) were PET-NEG; 206 (28%) were PET-POS. Time-to-progression (TTP) and overall survival (OS) at 3 years were 83% v 56% and 87% v 64%, for PET-NEG and PET-POS patients, respectively. Non-progressing PET-POS patients treated with consolidative RT (109/206, 53%) had outcomes approaching those of PET-NEG patients, with 3-year estimates of 76% and 80% for TTP and OS. PET-NEG patients with bulky disease (≥10 cm) at diagnosis, had outcomes indistinguishable from those without bulk, despite omitting RT. These data suggest that patients with advanced-stage DLBCL that are PET-NEG at EOT and receive no RT have excellent outcomes. FDG-PET can reliably guide selective administration of consolidative RT, even for patients with initially bulky disease.

Description: Introduction Many pts with advanced (adv) stage follicular lymphoma (FL) present with low burden asymptomatic disease and are suitable for observation. Previous studies have shown that rituximab can delay the need for definitive therapy in these pts (Ardeshna et al, Lancet Oncol 2014), and that rituximab maintenance does not offer a long-term advantage (Kahl et al, JCO 2014). Based on early results of these trials, BC Cancer endorsed the use of rituximab monotherapy (R-mono), administered as 4 weekly doses for pts with newly diagnosed asymptomatic adv stage FL in British Columbia in 2011. The aim of this study was to assess the benefit of R-mono and to compare outcomes to pts undergoing observation (OBSE) prior to the introduction of R-mono (OBSE-1) or since the availability of R-mono (OBSE-2). Methods The BC Cancer Lymphoid Cancer and Provincial Pharmacy Databases were used to identify all pts 〉16 y of age with newly diagnosed, adv stage (extensive stage 2-4), asymptomatic (low tumour burden), grades 1-3a FL betw Jan 2011-Aug 2019, who were treated with R-mono. Results were compared with two OBSE cohorts with similar clinical inclusion criteria; a historical cohort (OBSE-1) diagnosed Jan 2004-Dec 2010 and a current-era cohort (OBSE-2) diagnosed Jan 2011-Aug 2019. Use of R-mono was at the discretion of the treating physician and reflected patient preference. The primary endpoint was time-to-new treatment (TTNT), measured from date of diagnosis to start of any therapy following R-mono or OBSE (systemic, radiotherapy or splenectomy); pts who did not need new treatment were censored at last follow-up. Clinical factors were compared using chi-square tests, ANOVA, and Kruskal-Wallis tests. Kaplan-Meier curves were used to generate survival estimates and differences between cohorts were examined using a log-rank test. Multivariable cox proportional hazard models were used to estimate hazard ratios for each cohort adjusting for relevant clinical factors, including the FLIPI group. Results In total, 843 pts were identified; R-mono (n=301), OBSE-1 (n=302), OBSE-2 (n=240). Median f/up was longer for OBSE-1 (12.1y, range 0.2-16.2), compared with R-mono (4.5y, 0.1-8.8) and OBSE-2 (4.3y, 0.4-9.3). Median time from diagnosis to R-mono was 0.21y (range, 0.05-1.06). Clinical characteristics were largely comparable betw the historical (OBSE-1) and current-era cohorts (R-mono + OBSE-2). However, in the current era, pts receiving R-mono were slightly younger and more likely to have stage 3/4 disease than OBSE-2 pts, indicating a possible selection bias in the use of R-mono (Table). Of the 301 pts receiving R-mono, 298 were evaluable for response, with 210 (70%) achieving CR(u), 70 (23%) PR, and 18 with non-response (2 stable disease, 16 progression, 6%). 10/18 R-mono non-responders developed transformed disease, with significantly poorer OS than responders (p

Description: Background: Richter transformation (RT) to diffuse large B-cell lymphoma (DLBCL) is a well-known complication of CLL/SLL, occurring in 2-10% of patients (pts); however, a minority transform to Hodgkin lymphoma, termed Hodgkin variant of RT (HvRT). Because of the rarity of HvRT, there is limited information regarding prognostic factors and treatment approach. The aim of this study was to evaluate clinical characteristics, treatment and survival of HvRT in a population based cohort of CLL/SLL pts in BC. Methods: Provincial databases were retrospectively reviewed from Jan. 1994 - Feb. 2020 to identify all CLL/SLL pts in BC with histologically proven HvRT using central pathology review. Overall survival (OS) was defined from HL diagnosis to death/last follow-up (f/u); progression-free survival (PFS) was defined from HL diagnosis to lymphoma progression, death or last f/u. Results: 32 pts with HvRT from CLL (N=18) or SLL (N=14) were identified. Median f/u for living pts from CLL/SLL diagnosis was 129 months (mos) (range, 25-504). Most pts were male (87%) with median age at CLL/SLL and HL diagnoses of 64 years (y) (range, 35-83) and 71 y (range, 51-86), respectively. Median interval from CLL/SLL diagnosis to HvRT was 67 mos (range, 0-403), with composite CLL/SLL and HL diagnosed in 5 pts (16%). At CLL/SLL diagnosis, 50% (15/30) had Rai or Ann Arbor stage 3-4; 7% (1/14) had del(17p), 29% (4/14) del(13q), 0% (0/14) del(11q), 29% (4/14) trisomy 12 and 50% (7/14) had no abnormalities. Most pts (80%; 24/30) had treatment for CLL/SLL prior to HvRT: purine analogues (PA) in 67% (20/30), alkylators in 50% (15/30), rituximab in 60% (18/30) and ibrutinib in 17% (5/30%). Median number of treatment lines prior to HvRT was 2 (range, 0-4) and median time from last CLL/SLL therapy to HvRT was 15 mos (range, 1-107). HvRT was characterized by Ann Arbor stage 3-4 in 87% (25/29) of cases, B symptoms in 67% (18/27), International Prognostic Score (IPS) ≥ 4 in 67% (18/27), and Epstein Barr virus (EBV) positivity in 59% (13/22). Richter Prognosis Score (RPS) was low risk (RPS 0-1) in 48% (10/21 pts), low-intermediate (RPS 2) in 33% (7/21) and high-int/high (RPS 3-5) in 19% (4/21). ABVD (adriamycin, bleomycin, vinblastine and dacarbazine) or ABVD-like therapy (AVD or modified ABVD dose/regimen) was the most common primary HL therapy, used in 65% (20/31). Others were alkylator-based regimens in 13% (4/31); brentuximab, ibrutinib and cyclosporine in 1 case each, and local excision in 1 case. 4 pts had radiotherapy for primary (N=2) or relapsed HL (N=2). No pts had autologous stem cell transplant (SCT); however, 1 had a reduced intensity allogeneic SCT 10.8 mos after HvRT. 3 pts (10%) had no HL therapy due to frailty. Median f/u for living pts from HvRT was 25 mos (range, 4-100). 18 pts (56%) experienced lymphoma progression: 5 CLL/SLL, 8 HL, 1 with a second RT to DLBCL and 4 with unknown subtype. One pt, who first progressed with CLL after HvRT, subsequently developed a second RT to DLBCL. At time of last f/u, 75% of pts (24/32) died. Cause of death was lymphoma in 14 pts (3 CLL/SLL; 7 HL; 2 DLBCL; 2 unknown subtype), treatment-related toxicity in 5, secondary malignancy in 2, other causes in 2 and unknown cause in 1. The 2 y OS and PFS from HvRT were 55% (95% CI: 36-71%) and 46% (95% CI: 28-62%), respectively, Fig. 1A-B. Factors at HvRT significantly affecting OS included low hemoglobin (〈 120 vs ≥ 120 x 109/L, P=.02), elevated lactate dehydrogenase (elevated vs normal, P=.04), high IPS (IPS ≥ 4 vs 〈 4, P=.04), and, among pts who received chemotherapy (N=27), primary HL therapy (non-ABVD vs ABVD/ABVD-like, P=.048). The only factor significantly associated with PFS was primary HL treatment (P12 mos, P=.72), prior treatment for CLL (P=0.15), prior PA therapy (P=.14), B symptoms at HvRT (P=0.12), EBV positivity (P=.24) and RPS (0-2 vs 3-5, P=.85) did not significantly impact OS or PFS. Conclusion: In this real-world population-based cohort of CLL/SLL pts, HvRT was associated with poor clinical outcomes, with a median OS less than 3 y from time of HvRT. This may be in part due to the older age of HvRT diagnosis, which limits the ability to give curative therapy with ABVD. Further biological and clinical investigation of this rare entity, particularly in the era of novel agents, is warranted to improve outcomes. Disclosures Villa: Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; AZ: Consultancy, Honoraria, Research Funding; Kite/Gilead: Consultancy, Honoraria; Nano String: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Sandoz Canada: Consultancy, Honoraria; Immunovaccine: Consultancy, Honoraria; Purdue Pharma: Consultancy, Honoraria. Scott:NIH: Consultancy, Other: Co-inventor on a patent related to the MCL35 assay filed at the National Institutes of Health, United States of America.; Roche/Genentech: Research Funding; Abbvie: Consultancy; AstraZeneca: Consultancy; Janssen: Consultancy, Research Funding; NanoString: Patents & Royalties: Named inventor on a patent licensed to NanoString, Research Funding; Celgene: Consultancy. Sehn:Takeda: Consultancy, Honoraria; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding; MorphoSys: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Acerta: Consultancy, Honoraria; Genentech, Inc.: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; Apobiologix: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Servier: Consultancy, Honoraria; TG therapeutics: Consultancy, Honoraria; Chugai: Consultancy, Honoraria; Verastem Oncology: Consultancy, Honoraria; Teva: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Connors:Seattle Genetics: Other: Sponsorship to educational presentations; Takeda: Other: Sponsorship to educational presentations. Toze:Janssen: Consultancy. Savage:Merck, BMS, Seattle Genetics, Gilead, AstraZeneca, AbbVie, Servier: Consultancy; BeiGene: Other: Steering Committee; Merck, BMS, Seattle Genetics, Gilead, AstraZeneca, AbbVie: Honoraria; Roche (institutional): Research Funding. Gerrie:Roche: Research Funding; Sandoz: Consultancy; Astrazeneca: Consultancy, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding.