Outcomes of patients with limited-stage plasmablastic lymphoma: A multi-institutional retrospective study

Plasmablastic lymphoma (PBL) is a rare entity, commonly associated with immunosuppressed states such as human immunodeficiency virus (HIV) infection or solid organ transplant. The clinical course is characterized by high relapse rates and a poor prognosis, leading some clinicians to recommend aggressive frontline therapy. However, a specific review of limited stage (LS) PBL patients is not available to evaluate outcomes and justify treatment recommendations. We performed a retrospective review of LS PBL cases to provide insight into this rare disease. Our cohort consisted of 80 stage I or II PBL patients from 13 US academic centers. With a median follow up of 34 months (1-196), the 3-year progression-free survival (PFS) and overall survival (OS) of the entire cohort were 72% (95% CI 62, 83) and 79% (95% CI 70, 89), respectively. The 3-year PFS and OS of patients treated with frontline chemotherapy alone was 65% (95% CI 50, 84) and 71% (95% CI 56, 89), respectively, compared to 85% (95% CI 72, 100) and 96% (95% CI 89, 100), respectively, in patients treated with combined frontline chemotherapy with radiation consolidation. Our data demonstrate favorable outcomes in LS PBL with no improvements in outcome from aggressive frontline treatment including Hyper-CVAD or auto-SCT consolidation. Multivariate regression analysis (MRA) demonstrated improved PFS for patients receiving EPOCH based frontline therapy versus CHOP (HR: 0.23; p = 0.029). Frontline chemotherapy followed by radiation consolidation versus chemotherapy alone appeared to be associated with improved relapse and survival outcomes but did not show statistical significance in MRA

Outcomes of Patients with Limited-Stage Plasmablastic Lymphoma

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

The Evaluation and Treatment (Tx) of Burkitt Lymphoma (BL) in the Modern Era: Real World (RW) Outcomes and Prognostication across 26 US Cancer Centers (CC)

Introduction: Historically, outcomes for BL have improved in adults using dose intensive chemotherapy regimens and early CNS prophylaxis. More recent data using a less intensive regimen, DA-EPOCH, have been reported. We analyzed detailed patient (pt) & disease characteristics and treatment patterns across 26 US CCs over a recent 9 year (yr) period and also determined survival rates & prognostication. Methods: We conducted a large multicenter retrospective study of newly diagnosed (dx) adult BL pts (6/2009 - 6/2018). Dx was established by institutional expert pathology review; all cases were verified for BL based on 2016 WHO criteria (high grade B cell lymphoma, BL like, etc were excluded). Survival rates were estimated by Kaplan-Meier with differences assessed by log rank test. Univariate (UVA) associations were derived via Cox model with variables P ≤0.05 entered stepwise into a multivariate (MVA) model. Using significant factors from the MVA, a prognostic survival model was constructed. Results: Among N=557 verified BL cases, clinical features included: median age 47 yrs (17-88 yrs; 24% ≥60 yrs); male 76%; HIV+ 22%; ECOG PS 0/1 76%; B symptoms 51%; elevated LDH 78% (3, 5, & 10x elevation: 44%, 29% & 15%, respectively); hemoglobin 1 EN 43%; and 76% stage 3-4 disease (10% stage 1). Additionally, 16% and 3% of pts had baseline leptomeningeal (CSF or cranial nerve palsy) or parenchymal CNS involvement, respectively (see Zayac A et al. ASH 2019 for details). For MYC partner, 68% had t(8;14), 4% light chain, 5% negative FISH (otherwise classic BL) and 23% + break apart probe. HIV+ pts had several clinical differences: CSF+ 23% vs 12% P=0.003; CNS 19% vs 8% P1 EN 60% vs 38% P3x normal (Fig 1B/C). Notably, survival rates were not different based on HIV status (Fig 1D) or by the 3 most common Tx regimens (Fig 1E). However, there were important Tx differences based on presence of CNS involvement (see Zayac A et al. ASH 2019). Additionally, use of rituximab was associated with improved PFS & OS (Fig 1F), while outcomes were similar whether rituximab was given inpt vs outpatient (inpt PFS HR 1.25, P=0.19). Furthermore, Tx at an academic CC was associated with improved outcomes, which persisted on MVA (PFS HR 0.54, 95%CI 0.33-0.88 P=0.01; OS HR 0.50, 95%CI 0.29-0.87 P=0.01) & achievement of initial CR was strongly prognostic (Fig 1G). Baseline factors significant on UVA for PFS & OS were: age ≥40 yrs; PS 2-4; LDH >3x; anemia, low albumin; BM involvement; Stage 3-4; CSF+; & >1 EN. On MVA, factors associated with inferior survival were: age ≥40 yrs (PFS HR 1.57, P3x (PFS HR 2.28, P<0.0001; OS HR 1.96, P<0.0001). Collectively, these factors yielded a BL survival model (Fig 1H/I). Conclusions: Outcomes for adult BL in this contemporary, large, multicenter RW analysis appear inferior to smaller published series. Interestingly, despite increased adverse prognostic factors, survival rates appeared similar in HIV+ pts. In addition, use of rituximab, achievement of initial CR, and Tx at an academic CC were associated with improved survival. Finally, a novel BL-specific survival model identified pts with markedly divergent outcomes. Disclosures Evens: Seattle Genetics: Consultancy, Honoraria, Research Funding; Epizyme: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria; Tesaro: Research Funding; Verastem: Consultancy, Honoraria. Danilov:Janssen: Consultancy; Seattle Genetics: Consultancy; MEI: Research Funding; Abbvie: Consultancy; Pharmacyclics: Consultancy; Takeda Oncology: Research Funding; Janssen: Consultancy; TG Therapeutics: Consultancy; Curis: Consultancy; Pharmacyclics: Consultancy; Aptose Biosciences: Research Funding; Verastem Oncology: Consultancy, Other: Travel Reimbursement , Research Funding; AstraZeneca: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Bayer Oncology: Consultancy, Research Funding; Celgene: Consultancy; Bristol-Meyers Squibb: Research Funding; MEI: Research Funding; Gilead Sciences: Consultancy, Research Funding; Abbvie: Consultancy; Bristol-Meyers Squibb: Research Funding. Reddy:KITE Pharma: Consultancy; BMS: Consultancy, Research Funding; Celgene: Consultancy; Genentech: Research Funding; Abbvie: Consultancy. Farooq:Celgene: Honoraria; Kite Pharma: Research Funding. Khan:Janssen: Other: Educational Content/Symposium; Abbvie: Membership on an entity's Board of Directors or advisory committees; Bristol Myers: Other: Research Funds; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Yazdy:Genentech: Research Funding; Bayer: Honoraria; Abbvie: Consultancy; Octapharma: Consultancy. Karmali:Gilead/Kite; Juno/Celgene: Consultancy, Speakers Bureau; Astrazeneca: Speakers Bureau; Takeda, BMS: Other: Research Funding to Institution. Martin:Janssen: Consultancy; Teneobio: Consultancy; Celgene: Consultancy; Karyopharm: Consultancy; Sandoz: Consultancy; I-MAB: Consultancy. Diefenbach:LAM Therapeutics: Research Funding; Incyte: Research Funding; Genentech: Consultancy, Research Funding; Trillium: Research Funding; Millenium/Takeda: Research Funding; Seattle Genetics: Consultancy, Research Funding; Merck: Consultancy, Research Funding; MEI: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Denovo: Research Funding. Epperla:Pharmacyclics: Honoraria; Verastem Oncology: Speakers Bureau. Feldman:Eisai: Research Funding; Amgen: Research Funding; Cell Medica: Research Funding; Roche: Research Funding; Corvus: Research Funding; Kyowa Hakko Kirin: Research Funding; Pfizer: Research Funding; Trillium: Research Funding; Viracta: Research Funding; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Other: Travel expenses, Speakers Bureau; AbbVie: Honoraria, Other: Travel expenses, Speakers Bureau; Pharmacyclics: Honoraria, Other: Travel expenses, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Kite Pharma: Honoraria, Other: Travel expenses, Speakers Bureau; Portola Pharma: Research Funding; Roche: Research Funding. Lossos:Janssen Scientific: Membership on an entity's Board of Directors or advisory committees; NIH: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Naik:Celgene: Other: Advisory board. Kamdar:Celgene: Consultancy; AstraZeneca: Consultancy; Seattle Genetics: Speakers Bureau; University of Colorado: Employment; Pharmacyclics: Consultancy. Portell:AbbVie: Research Funding; Pharmacyclics: Consultancy; Janssen: Consultancy; Genentech: Consultancy, Research Funding; Bayer: Consultancy; BeiGene: Consultancy, Research Funding; Kite: Consultancy, Research Funding; Acerta/AstraZeneca: Research Funding; TG Therapeutics: Research Funding; Xencor: Research Funding; Roche/Genentech: Research Funding; Infinity: Research Funding; Amgen: Consultancy. Olszewski:Spectrum Pharmaceuticals: Research Funding; TG Therapeutics: Research Funding; Genentech: Research Funding; Adaptive Biotechnologies: Research Funding. Alderuccio:Agios: Other: Immediate family member; Puma Biotechnology: Other: Immediate family member; Foundation Medicine: Other: Immediate family member; Targeted Oncology: Honoraria; Inovio Pharmaceuticals: Other: Immediate family member; OncLive: Consultancy

Outcomes of Patients with Newly-Diagnosed Burkitt Lymphoma (BL) and Central Nervous System (CNS) Involvement Treated in the Modern Era: A Multi-Institutional Real-World Analysis

Background: BL is associated with a high risk of primary or secondary CNS involvement, warranting intrathecal (IT) and/or systemic therapy that penetrates the blood-brain barrier (BBB). The lower-intensity DA-EPOCH-R regimen has recently shown high survival rates in BL (Dunleavy, NEJM 2013), but it omits drugs traditionally used for CNS prophylaxis (like high-dose methotrexate [HDMTX]). The objective of this multi-institutional retrospective study was to examine treatments, risk factors, and CNS-related outcomes among patients (pts) with BL. Methods: We collected data from 26 US centers on adult BL pts diagnosed (dx) in 6/2009-6/2018. Using institutional expert pathology review and 2016 WHO criteria, we excluded other high-grade lymphomas (including BL-like/unclassifiable), or cases with inadequate clinicopathologic data. We studied factors associated with baseline CNS involvement (CNSinv) using logistic regression reporting odds ratios (OR). Progression-free (PFS), overall survival (OS), and cumulative incidence function of CNS recurrence (in a competing risk analysis) were examined in Cox or Fine-Gray models reporting hazard (HR) or subhazard ratios (SHR), respectively. All estimates report 95% confidence intervals (in square brackets). Results: Among 557 BL pts (median age, 47 years [yr], 24% women, 23% HIV+), 107 (19%) had CNSinv at dx, including 89 (16%) with leptomeningeal, and 15 (3%) with parenchymal CNS disease. In a multivariable model, factors significantly associated with CNSinv at dx included stage 3/4 (OR, 11.2 [1.47-85.9]), poor performance status (PS; OR, 2.12 [1.22-3.69]), ≥2 extranodal sites (OR, 3.77 [2.02-7.03]), or marrow involvement (OR, 2.44 [1.35-4.39]), whereas intestinal involvement conferred low risk of CNSinv (OR, 0.27 [0.11-0.65]). CNSinv at dx was not significantly associated with use of specific chemotherapy regimens (Fig. A,P=.75) or receipt of IT chemotherapy (91% vs 84%, P=.065). Pts with CNSinv were less likely to achieve a complete response (62% vs 76%, P=.005), had worse 3 yr PFS (47% vs 69%; P3x upper limit of normal [LDH>3x]; see Evens AM et al, ASH 2019 for further details). With median follow up of 3.6 yrs, 33 pts (6%) experienced a CNS recurrence (82% within 1 yr from dx; 79% purely in CNS, and 21% with concurrent systemic BL). The cumulative risk of CNS recurrence was 6% [4-8%] at 3y (Fig. D). Univariate significant predictors of CNS recurrence included baseline CNSinv, HIV+ status, stage 3/4, poor PS, LDH>3x, involvement of ≥2 extranodal sites, marrow, or testis. However, in a multivariate model only baseline CNSinv (SHR, 3.35 [1.53-7.31]) and poor PS (SHR, 2.24 [1.03-4.90]) retained significance. The 3 yr risk of CNS recurrence varied from 3% for pts with no risk factor, to 10% with one, and 17% with both factors (Fig. E). In addition, the risk of CNS recurrence differed according to chemotherapy regimen, and was significantly higher for pts treated with DA-EPOCH (12% at 3y [8-18%]; Fig. F) compared with CODOX-M/IVAC (4% [2-8%]) or hyperCVAD/MA (3% [1-6%]; SHR for DA-EPOCH vs. others, 3.50 [1.69-7.22]). All pts recurring after DA-EPOCH had received IT chemotherapy. Higher risk of CNS recurrence persisted with DA-EPOCH regardless of baseline CNSinv (Pinteraction=.70), poor PS (Pint=.14), or HIV status (Pint=.89). Baseline CNSinv was the strongest factor associated with CNS recurrence after DA-EPOCH (3 yr risk, 30% vs 8%, P<.001). Of 7 pts who received HDMTX with DA-EPOCH (6 with leptomeningeal CNSinv at dx), 3 (43%) experienced CNS recurrence. Median OS among all BL pts with CNS recurrence was 2.8 months [1.9-3.9] (Fig. G). After recurrence, 67% of pts received salvage systemic and 9% IT chemotherapy, 3% radiation, and 21% hospice care. Conclusions: In adult BL, baseline CNSinv and poor PS predicted subsequent CNS recurrence, an outcome that is associated with a dismal prognosis. Furthermore, treatment with DA-EPOCH was associated with a significantly increased risk of CNS recurrence in this real-world analysis. For BL pts with baseline CNSinv treated in routine clinical practice, regimens with highly BBB-penetrant drugs (e.g. CODOX-M/IVAC, hyperCVAD/MA) may be preferred. Studies should delineate ways to mitigate the risk of CNS recurrence with lower-intensity programs. Disclosures Evens: Seattle Genetics: Consultancy, Honoraria; Research to Practice: Honoraria; Verastem: Consultancy, Honoraria; Affimed: Consultancy, Honoraria; Pharmacyclics: Honoraria, Other: DMC; Bayer: Consultancy, Honoraria; Takeda: Research Funding; Merck: Research Funding. Smith:Incyte Corporation: Research Funding; Seattle Genetics: Research Funding; Portola Pharmaceuticals: Research Funding; Pharmacyclics: Research Funding; Acerta Pharma BV: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Research Funding; Ignyta (spouse): Research Funding; Merck Sharp & Dohme Corp: Consultancy, Research Funding; Denovo Biopharma: Research Funding; Bristol-Myers Squibb (spouse): Research Funding; Ayala (spouse): Research Funding. Naik:Celgene: Other: Advisory board. Reddy:KITE Pharma: Consultancy; Abbvie: Consultancy; Genentech: Research Funding; BMS: Consultancy, Research Funding; Celgene: Consultancy. Farooq:Celgene: Honoraria; Kite Pharma: Research Funding. Epperla:Verastem Oncology: Speakers Bureau; Pharmacyclics: Honoraria. Khan:Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Janssen: Other: Educational Content/Symposium; Abbvie: Membership on an entity's Board of Directors or advisory committees; Bristol Myers: Other: Research Funds. Alderuccio:Puma Biotechnology: Other: Immediate family member; Agios: Other: Immediate family member; Inovio Pharmaceuticals: Other: Immediate family member; Targeted Oncology: Honoraria; OncLive: Consultancy; Foundation Medicine: Other: Immediate family member. Yazdy:Bayer: Honoraria; Genentech: Research Funding; Octapharma: Consultancy; Abbvie: Consultancy. Diefenbach:Bristol-Myers Squibb: Consultancy, Research Funding; Denovo: Research Funding; Genentech: Consultancy, Research Funding; Incyte: Research Funding; LAM Therapeutics: Research Funding; MEI: Research Funding; Merck: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Millenium/Takeda: Research Funding; Trillium: Research Funding. Karmali:Astrazeneca: Speakers Bureau; Takeda, BMS: Other: Research Funding to Institution; Gilead/Kite; Juno/Celgene: Consultancy, Speakers Bureau. Martin:Celgene: Consultancy; Teneobio: Consultancy; Karyopharm: Consultancy; Janssen: Consultancy; Sandoz: Consultancy; I-MAB: Consultancy. Magarelli:Tevan Oncology: Speakers Bureau. Kamdar:Seattle Genetics: Speakers Bureau; Pharmacyclics: Consultancy; AstraZeneca: Consultancy; Celgene: Consultancy; University of Colorado: Employment. Portell:Xencor: Research Funding; Roche/Genentech: Research Funding; Infinity: Research Funding; TG Therapeutics: Research Funding; AbbVie: Research Funding; Pharmacyclics: Consultancy; Janssen: Consultancy; Genentech: Consultancy, Research Funding; Amgen: Consultancy; Bayer: Consultancy; BeiGene: Consultancy, Research Funding; Kite: Consultancy, Research Funding; Acerta/AstraZeneca: Research Funding. Lossos:Janssen Scientific: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; NIH: Research Funding. Olszewski:Genentech: Research Funding; Adaptive Biotechnologies: Research Funding; TG Therapeutics: Research Funding; Spectrum Pharmaceuticals: Research Funding

Outcomes of Burkitt lymphoma with central nervous system involvement: evidence from a large multi-center cohort study

Central nervous system (CNS) involvement in Burkitt lymphoma (BL) poses a major therapeutic challenge, and the relative ability of contemporary regimens to treat CNS involvement remains uncertain. We described prognostic significance of CNS involvement and incidence of CNS recurrence/progression after contemporary immunochemotherapy using real-world clinicopathologic data on adults with BL diagnosed between 2009 and 2018 across 30 US institutions. We examined associations between baseline CNS involvement, patient characteristics, complete response (CR) rates, and survival. We also examined risk factors for CNS recurrence. Nineteen percent (120/641) of patients (age 18-88 years) had CNS involvement. It was independently associated with HIV infection, poor performance status, involvement of ≥2 extranodal sites, or bone marrow involvement. First-line regimen selection was unaffected by CNS involvement (P=0.93). Patients with CNS disease had significantly lower rates of CR (59% versus 77% without; P

Burkitt lymphoma in the modern era: real-world outcomes and prognostication across 30 US cancer centers

We examined adults with untreated Burkitt lymphoma (BL) from 2009 to 2018 across 30 US cancer centers. Factors associated with progression-free survival (PFS) and overall survival (OS) were evaluated in univariate and multivariate Cox models. Among 641 BL patients, baseline features included the following: median age, 47 years; HIV+, 22%; Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2 to 4, 23%; >1 extranodal site, 43%; advanced stage, 78%; and central nervous system (CNS) involvement, 19%. Treatment-related mortality was 10%, with most common causes being sepsis, gastrointestinal bleed/perforation, and respiratory failure. With 45-month median follow-up, 3-year PFS and OS rates were 64% and 70%, respectively, without differences by HIV status. Survival was better for patients who received rituximab vs not (3-year PFS, 67% vs 38%; OS, 72% vs 44%; P 3× normal (PFS, HR = 1.83, P < .001; OS, HR = 1.63, P = .009), and CNS involvement (PFS, HR = 1.52, P = .017; OS, HR = 1.67, P = .014) predicted inferior survival. Furthermore, survival varied based on number of factors present (0, 1, 2 to 4 factors) yielding 3-year PFS rates of 91%, 73%, and 50%, respectively; and 3-year OS rates of 95%, 77%, and 56%, respectively. Collectively, outcomes for adult BL in this real-world analysis appeared more modest compared with results of clinical trials and smaller series. In addition, clinical prognostic factors at diagnosis identified patients with divergent survival rates

HIV-associated Burkitt lymphoma: outcomes from a US-UK collaborative analysis

Abstract Data addressing prognostication in patients with HIV related Burkitt lymphoma (HIV-BL) currently treated remain scarce. We present an international analysis of 249 (United States: 140; United Kingdom: 109) patients with HIV-BL treated from 2008 to 2019 aiming to identify prognostic factors and outcomes. With a median follow up of 4.5 years, the 3-year progression-free survival (PFS) and overall survival (OS) were 61% (95% confidence interval [CI] 55% to 67%) and 66% (95%CI 59% to 71%), respectively, with similar results in both countries. Patients with baseline central nervous system (CNS) involvement had shorter 3-year PFS (36%) compared to patients without CNS involvement (69%; P 5 upper limit of normal (HR 2.09; P 1 extranodal sites (HR 1.58; P = .043). The same variables were significant in multivariate models for OS. Adjusting for these prognostic factors, treatment with cyclophosphamide, vincristine, doxorubicin, and high-dose methotrexate, ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) was associated with longer PFS (adjusted HR [aHR] 0.45; P = .005) and OS (aHR 0.44; P = .007). Remarkably, HIV features no longer influence prognosis in contemporaneously treated HIV-BL

Prognostication, Survival and Treatment-Related Outcomes in HIV-Associated Burkitt Lymphoma (HIV-BL): A US and UK Collaborative Analysis

Introduction: There are few data about prognostication and outcomes in patients (pts) with HIV-BL treated in the cART era. Optimal treatment strategies to minimize treatment-related mortality (TRM) remain unclear and current recommendations are based on small studies. We conducted a multicenter international analysis to identify prognostic factors and outcomes in pts with HIV-BL treated in the cART era. Methods: This retrospective analysis included a subcohort from a recent study across 30 US sites (Evens et al. Blood 2020) augmented by data from 5 UK centers treated 2009-2018. Progression-free (PFS) and overall survival (OS) were estimated by Kaplan-Meier & differences assessed by log-rank test. Univariate (UVA) associations were derived via Cox model and multivariable (MVA) models were constructed by forward selection of significant variables with P 3x upper limit of normal (ULN) 49% & >5xULN 39%); >1 extranodal (EN) site: 60%; any CNS involvement (CNSinv) 25%; and +bone marrow (BM) 46%. MYC rearrangement was reported in 93% of pts with t(8;14) in 49%, break-apart probe in 41% and MYC-light chain in 3%; the rest had classical BL with negative MYC testing (4%) or missing result (3%) (otherwise classical BL). Median CD4 count was 217 (IQR 90-392 cells/µL) with 68% pts having CD4>100 cells/µL. At BL diagnosis, HIV viral load was detectable in 55%; 39% of pts were on cART. Baseline features were similar between the US & UK cohorts with significant differences only in ECOG PS 2-4 (32% vs 65%; P100 cells/µL had better 3-yr PFS (Fig B) & OS (68% vs 57% P=0.03). We observed significantly worse outcomes in pts with baseline CNSinv (3-yr PFS 36% vs 69%, P1 EN, +BM, baseline CNSinv, LDH>ULN, CD4 5xULN (HR 2.09, P1 EN sites (HR 1.58 P=0.043). The same variables were significant on MVA for OS. Adjusting for all of the prognostic variables, Tx with Magrath was associated with longer PFS (adjusted HR, 0.45, P=0.005). Conclusions: These data represent the largest analysis of HIV-BL to date. There were favorable tolerance and outcomes with intensive R-containing regimens with Magrath being associated with lower TRM and the highest PFS. In addition, prognostic factors for pt outcomes were associated with lymphoma characteristics rather than with HIV-related features. Pts with baseline CNSinv represent a high-risk group with unmet therapeutic needs. Disclosures Alderuccio: Oncinfo: Honoraria; Puma Biotechnology: Other: Family member; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; OncLive: Honoraria; Inovio Pharmaceuticals: Other: Family member; Foundation Medicine: Other: Family member; Forma Therapeutics: Other: Family member; Agios Pharmaceuticals: Other: Family member. Olszewski:Spectrum Pharmaceuticals: Research Funding; TG Therapeutics: Research Funding; Adaptive Biotechnologies: Research Funding; Genentech, Inc.: Research Funding. Evens:Epizyme: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria; Merck: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria; Mylteni: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria, Research Funding; MorphoSys: Consultancy, Honoraria; Research To Practice: Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria. Collins:Gilead: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; MSD: Consultancy, Honoraria, Research Funding; Taekda: Consultancy, Honoraria, Other: travel, accommodations, expenses, Speakers Bureau; BeiGene: Consultancy; Roche: Consultancy, Honoraria, Other: travel, accommodations, expenses , Speakers Bureau; Celleron: Consultancy, Honoraria, Research Funding; ADC Therapeutics: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Speakers Bureau; Celgene: Research Funding; Amgen: Research Funding; Pfizer: Honoraria. Danilov:Astra Zeneca: Consultancy, Research Funding; Verastem Oncology: Consultancy, Research Funding; Takeda Oncology: Research Funding; Gilead Sciences: Research Funding; Bayer Oncology: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; TG Therapeutics: Consultancy; Nurix: Consultancy; Celgene: Consultancy; Aptose Biosciences: Research Funding; Bristol-Myers Squibb: Research Funding; Rigel Pharmaceuticals: Consultancy; Karyopharm: Consultancy; Pharmacyclics: Consultancy; BeiGene: Consultancy; Abbvie: Consultancy. Jagadeesh:Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Debiopharm Group: Research Funding; MEI Pharma: Research Funding; Verastem: Membership on an entity's Board of Directors or advisory committees; Regeneron: Research Funding. Reddy:Genentech: Research Funding; Abbvie: Consultancy; BMS: Consultancy, Research Funding; Celgene: Consultancy; KITE Pharma: Consultancy. Farooq:Kite, a Gilead Company: Honoraria. Bond:Seattle Genetics: Honoraria. Khan:Celgene: Research Funding; Janssen: Honoraria; Pharmacyclics: Honoraria; Bristol Myers Squibb: Research Funding; Seattle Genetics: Research Funding. Yazdy:Bayer: Honoraria; Genentech: Research Funding; Octapharma: Consultancy; Abbvie: Consultancy. Karmali:Karyopharm: Honoraria; Takeda: Research Funding; AstraZeneca: Speakers Bureau; BeiGene: Speakers Bureau; BMS/Celgene/Juno: Honoraria, Other, Research Funding, Speakers Bureau; Gilead/Kite: Honoraria, Other, Research Funding, Speakers Bureau. Martin:Janssen: Consultancy; Regeneron: Consultancy; Bayer: Consultancy; Sandoz: Consultancy; I-MAB: Consultancy; Beigene: Consultancy; Cellectar: Consultancy; Incyte: Consultancy; Kite: Consultancy; Morphosys: Consultancy; Celgene: Consultancy; Teneobio: Consultancy; Karyopharm: Consultancy, Research Funding. Diefenbach:Bristol-Myers Squibb: Consultancy, Research Funding; Denovo: Research Funding; Genentech, Inc.: Consultancy, Research Funding; Incyte: Research Funding; LAM Therapeutics: Research Funding; MEI: Research Funding; Merck: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Millenium/Takeda: Research Funding; Trillium: Research Funding. Klein:Takeda: Membership on an entity's Board of Directors or advisory committees. Haverkos:Viracta THerapeutics: Consultancy. Epperla:Verastem Oncology: Speakers Bureau; Pharmacyclics: Honoraria. Caimi:Amgen: Other: Advisory Board; Bayer: Other: Advisory Board; Kite Pharma: Other: Advisory Board; ADC Therapeutics: Other: Advisory Board, Research Funding; Celgene: Speakers Bureau; Verastem: Other: Advisory Board. Kamdar:Roche: Research Funding. Feldman:Eisai: Research Funding; Pfizer: Research Funding; Kyowa Kirin: Consultancy, Research Funding; Portola: Research Funding; Janssen: Speakers Bureau; AstraZeneca: Consultancy; Trillium: Research Funding; Cell Medica: Research Funding; Amgen: Research Funding; Pharmacyclics: Honoraria, Other, Speakers Bureau; Abbvie: Honoraria; Bayer: Consultancy, Honoraria; Viracta: Research Funding; Rhizen: Research Funding; Corvus: Research Funding; BMS: Consultancy, Honoraria, Research Funding; Kite: Honoraria, Other: Travel expenses, Speakers Bureau; Celgene: Honoraria, Research Funding; Takeda: Honoraria, Other: Travel expenses; Seattle Genetics, Inc.: Consultancy, Honoraria, Other: Travel expenses, Research Funding, Speakers Bureau. Smith:AstraZeneca: Consultancy; Millenium/Takeda: Consultancy; Karyopharm: Consultancy; Beigene: Consultancy; Seattle Genetics: Research Funding; Ayala: Research Funding; Bayer: Research Funding; AstraZeneca: Research Funding; Acerta Pharma BV: Research Funding; Bristol Meyers Squibb: Research Funding; Portola: Research Funding; Pharmacyclics: Research Funding; Merck: Research Funding; Incyte: Research Funding; Ignyta: Research Funding; Genentech: Research Funding; De Novo Biopharma: Research Funding. Portell:Amgen: Consultancy