Outcomes of Burkitt lymphoma with central nervous system involvement: Evidence from a large multicenter cohort study

Adam S. Zayac, Andrew M. Evens, Alexey Danilov, Stephen D. Smith, Deepa Jagadeesh, Lori A. Leslie, Catherine Wei, Seo Hyun Kim, Seema Naik, Suchitra Sundaram, Nishitha Reddy, Umar Farooq, Vaishalee P. Kenkre, Narendranath Epperla, Kristie A. Blum, Nadia Khan, Daulath Singh, Juan P. Alderuccio, Amandeep Godara, Maryam Sarraf YazdyCatherine Diefenbach, Emma Rabinovich, Gaurav Varma, Reem Karmali, Yusra Shao, Asaad Trabolsi, Madelyn Burkart, Peter Martin, Sarah Stettner, Ayushi Chauhan, Yun Kyong Choi, Allandria Straker-Edwards, Andreas Klein, Michael C. Churnetski, Kirsten M. Boughan, Stephanie Berg, Bradley M. Haverkos, Victor M. Orellana-Noia, Christopher D'Angelo, David A. Bond, Seth M. Maliske, Ryan Vaca, Gabriella Magarelli, Amy Sperling, Max J. Gordon, Kevin A. David, Malvi Savani, Paolo Caimi, Manali Kamdar, Matthew A. Lunning, Neil Palmisiano, Parameswaran Venugopal, Craig A. Portell, Veronika Bachanova, Tycel Phillips, Izidore S. Lossos, Adam J. Olszewski

Research output: Contribution to journalArticlepeer-review

Abstract

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<0.001), worse 3-year progression-free survival (adjusted hazard ratio [aHR], 1.53, 95% confidence interval [CI], 1.14-2.06, P=0.004) and overall survival (aHR, 1.62, 95%CI, 1.18-2.22, P=0.003). The 3-year cumulative incidence of CNS recurrence was 6% (95%CI, 4-8%). It was significantly lower among patients receiving other regimens (CODOX-M/IVAC, 4%, or hyperCVAD/MA, 3%) compared with DA-EPOCH-R (13%; adjusted sub-HR, 4.38, 95%CI, 2.16-8.87, P<0.001). Baseline CNS involvement in BL is relatively common and portends inferior prognosis independent of first-line regimen selection. In real-world practice, regimens with highly CNS-penetrant intravenous systemic agents were associated with a lower risk of CNS recurrence. This finding may be influenced by observed suboptimal adherence to the strict CNS staging and intrathecal therapy procedures incorporated in DA-EPOCH-R.

Original languageEnglish (US)
Pages (from-to)1932-1942
Number of pages11
JournalHaematologica
Volume106
Issue number7
DOIs
StatePublished - Jul 1 2021

Bibliographical note

Funding Information:
Verastem, Affimed and Bayer; and has received honoraria from and sat on a DMC for Pharmacyclics. AD has received research funding from Aptose Biosciences, Gilead Sciences, Takeda Oncology and Bristol-Myers Squibb; has received research funding and provided consultancy services for AstraZeneca, Genentech, Bayer Oncology and Verastem Oncology; has acted as a consultant for Beigene. TG Therapeutics, Celgene, Nurix and Rigel Pharmaceuticals; and is a Leukemia and Lymphoma Society Scholar in Clinical Research. SDS has received research funding from Incyte Corporation, Seattle Genetics, Portola Pharmaceuticals, Pharmacyclics, Acerta Pharma BV, Genentech and Denovo Biopharma; he has received research funding from and acted as a consultant for Merck Sharp & Dohme Corp; and he has been a member of Astra Zeneca’s Board of Directors or advisory committees and has received research funding from this company; a Astra Zeneca. An immediate family member has received research funding from Ignyta, Bristol-Myers Squibb and Ayala. SN has provided advisory board services for Celgene and Sanofi. NR has acted as a consultant for KITE Pharma, Abbvie and Celgene; has received research funding from Genentech; and has provided consultancy services for and received research funding from BMS. UF has received honoraria from Celgene and research funding from Kite Pharma. NE has received honoraria from Pharmacyclics and taken part in a speakers bureau for Verastem Oncology. NK has been a member of the Board of Directors or an advisory committee of Seattle Genetics and Abbvie; has received research funds from Bristol Myers; and has delivered educational content or symposia for Janssen. JPA has received honoraria from Targeted Oncology; and acted as a consultant for OncLive. An immediate family member has had contacts with Puma Biotechnology, Agios, Inovio Pharmaceuticals and Foundation Medicine. MSY has received honoraria from Bayer; has received research funding from Genentech; and has acted as a consultant for Octapharma and Abbvie. CD has received research funding from Denovo, Incyte, LAM Therapeutics, MEI, Millenium/Takeda and Trillium; and has acted as consultant for and received research funding from Bristol-Myers Squibb, Genentech, Merck and Seattle Genetics. RK has sat on speakers’ bureaus for Takeda, AstraZeneca and BeiGene; has supplied advisory board services

Funding Information:
AE has received research funding from Takeda and Merck; has received honoraria from Research to Practice; has received honoraria from and provided consultancy services for Seattle Genetics,

Publisher Copyright:
© 2021 Ferrata Storti Foundation

Keywords

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols/therapeutic use
  • Burkitt Lymphoma/diagnosis
  • Central Nervous System
  • Central Nervous System Neoplasms/diagnosis
  • Cohort Studies
  • Cyclophosphamide/therapeutic use
  • Disease-Free Survival
  • Doxorubicin/therapeutic use
  • HIV Infections
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Rituximab/therapeutic use
  • Young Adult

PubMed: MeSH publication types

  • Research Support, Non-U.S. Gov't
  • Multicenter Study
  • Journal Article

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