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

• Published in: Blood 2019-11, Vol.134 (Supplement_1), p.402-402
• Main Authors: Zayac, Adam, Evens, Andrew Matthew, Stadnik, Andrzej, Smith, Stephen D., Jagadeesh, Deepa, Leslie, Lori A., Wei, Catherine, Kim, Seo-Hyun, Naik, Seema, Sundaram, Suchitra, Reddy, Nishitha, Farooq, Umar, Kenkre, Vaishalee P., Epperla, Narendranath, Blum, Kristie A., Khan, Nadia, Singh, Daulath, Alderuccio, Juan Pablo, Godara, Amandeep, Yazdy, Maryam, Diefenbach, Catherine, Rabinovich, Emma, Varma, Gaurav, Karmali, Reem, Shao, Yusra, Trabolsi, Asaad, Burkart, Madelyn, Martin, Peter, Stettner, Sarah, Chauhan, Ayushi, Choi, Yun Kyong, Straker-Edwards, Allandria, Klein, Andreas, Churnetski, Michael C., Boughan, Kirsten M, Berg, Stephanie, Haverkos, Brad M., Orellana-Noia, Victor M., D'Angelo, Christopher, Bond, David A., Maliske, Seth M, Vaca, Ryan, Magarelli, Gabriela, Sperling, Amy, Gordon, Max J., David, Kevin A., Caimi, Paolo, Kamdar, Manali, Portell, Craig A., Venugopal, Parameswaran, Lossos, Izidore S., Olszewski, Adam J
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2019-122990

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]; 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