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 Yazdy; Catherine 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

doi:10.3324/haematol.2020.270876

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

^*Corresponding author for this work

Medicine, Hematology Oncology Division

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

Central nervous system (CNS) involvement in Burkitt lymphoma poses a major therapeutic challenge, and the relative ability of contemporary regimens to treat CNS involvement remains uncertain. We describe the prognostic significance of CNS involvement and the incidence of CNS recurrence/progression after contemporary immunochemotherapy using real-world clinicopathological data from adults with Burkitt lymphoma diagnosed between 2009 and 2018 in 30 institutions in the USA. We examined associations between baseline CNS involvement, patients' characteristics, complete response rates, and survival. We also examined risk factors for CNS recurrence. Of 641 patients (aged 18 to 88 years), 120 (19%) had CNS involvement. CNS involvement was independently associated with human immunodeficiency virus infection, poor performance status, involvement of ≥2 extranodal sites, and bone marrow involvement. Selection of the first-line treatment regimen was unaffected by CNS involvement (P=0.93). Patients with CNS disease had significantly lower rates of complete response (59% vs. 77% for patients with and without CNS involvement, respectively; P<0.001), worse 3-year progression-free survival (adjusted hazard ratio [aHR]=1.53, 95% confidence interval [95% 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%) and was significantly lower among patients receiving other regimens (CODOX-M/IVAC, 4%, or hyperCVAD/MA, 3%) compared with DA-EPOCH-R (13%; adjusted sub-distribution HR=4.38, 95% CI:, 2.16-8.87; P<0.001). Baseline CNS involvement in Burkitt lymphoma is relatively common and portends inferior prognosis independently of the first-line treatment regimen selected. In real-world practice, regimens including intravenous systemic agents with pronounced CNS penetrance 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 the DA-EPOCH-R regimen.

Original language	English (US)
Pages (from-to)	1932-1942
Number of pages	11
Journal	Haematologica
Volume	106
Issue number	7
DOIs	https://doi.org/10.3324/haematol.2020.270876
State	Published - Jul 2021

ASJC Scopus subject areas

Hematology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.3324/haematol.2020.270876

Cite this

Zayac, A. S., Evens, A. M., Danilov, A., Smith, S. D., Jagadeesh, D., Leslie, L. A., Wei, C., Kim, S. H., Naik, S., Sundaram, S., Reddy, N., Farooq, U., Kenkre, V. P., Epperla, N., Blum, K. A., Khan, N., Singh, D., Alderuccio, J. P., Godara, A., ... Olszewski, A. J. (2021). Outcomes of Burkitt lymphoma with central nervous system involvement: Evidence from a large multicenter cohort study. Haematologica, 106(7), 1932-1942. https://doi.org/10.3324/haematol.2020.270876

@article{d20c35509f63469a92191ae93b38bc0e,

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

abstract = "Central nervous system (CNS) involvement in Burkitt lymphoma poses a major therapeutic challenge, and the relative ability of contemporary regimens to treat CNS involvement remains uncertain. We describe the prognostic significance of CNS involvement and the incidence of CNS recurrence/progression after contemporary immunochemotherapy using real-world clinicopathological data from adults with Burkitt lymphoma diagnosed between 2009 and 2018 in 30 institutions in the USA. We examined associations between baseline CNS involvement, patients' characteristics, complete response rates, and survival. We also examined risk factors for CNS recurrence. Of 641 patients (aged 18 to 88 years), 120 (19%) had CNS involvement. CNS involvement was independently associated with human immunodeficiency virus infection, poor performance status, involvement of ≥2 extranodal sites, and bone marrow involvement. Selection of the first-line treatment regimen was unaffected by CNS involvement (P=0.93). Patients with CNS disease had significantly lower rates of complete response (59% vs. 77% for patients with and without CNS involvement, respectively; P<0.001), worse 3-year progression-free survival (adjusted hazard ratio [aHR]=1.53, 95% confidence interval [95% 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%) and was significantly lower among patients receiving other regimens (CODOX-M/IVAC, 4%, or hyperCVAD/MA, 3%) compared with DA-EPOCH-R (13%; adjusted sub-distribution HR=4.38, 95% CI:, 2.16-8.87; P<0.001). Baseline CNS involvement in Burkitt lymphoma is relatively common and portends inferior prognosis independently of the first-line treatment regimen selected. In real-world practice, regimens including intravenous systemic agents with pronounced CNS penetrance 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 the DA-EPOCH-R regimen.",

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

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{\textquoteright}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{\textquoteright} 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: {\textcopyright} 2021 Ferrata Storti Foundation",

year = "2021",

month = jul,

doi = "10.3324/haematol.2020.270876",

language = "English (US)",

volume = "106",

pages = "1932--1942",

journal = "Haematologica",

issn = "0390-6078",

publisher = "Ferrata Storti Foundation",

number = "7",

}

Zayac, AS, Evens, AM, Danilov, A, Smith, SD, Jagadeesh, D, Leslie, LA, Wei, C, Kim, SH, Naik, S, Sundaram, S, Reddy, N, Farooq, U, Kenkre, VP, Epperla, N, Blum, KA, Khan, N, Singh, D, Alderuccio, JP, Godara, A, Yazdy, MS, Diefenbach, C, Rabinovich, E, Varma, G, Karmali, R, Shao, Y, Trabolsi, A, Burkart, M, Martin, P, Stettner, S, Chauhan, A, Choi, YK, Straker-Edwards, A, Klein, A, Churnetski, MC, Boughan, KM, Berg, S, Haverkos, BM, Orellana-Noia, VM, D'Angelo, C, Bond, DA, Maliske, SM, Vaca, R, Magarelli, G, Sperling, A, Gordon, MJ, David, KA, Savani, M, Caimi, P, Kamdar, M, Lunning, MA, Palmisiano, N, Venugopal, P, Portell, CA, Bachanova, V, Phillips, T, Lossos, IS & Olszewski, AJ 2021, 'Outcomes of Burkitt lymphoma with central nervous system involvement: Evidence from a large multicenter cohort study', Haematologica, vol. 106, no. 7, pp. 1932-1942. https://doi.org/10.3324/haematol.2020.270876

TY - JOUR

T1 - Outcomes of Burkitt lymphoma with central nervous system involvement

T2 - Evidence from a large multicenter cohort study

AU - Zayac, Adam S.

AU - Evens, Andrew M.

AU - Danilov, Alexey

AU - Smith, Stephen D.

AU - Jagadeesh, Deepa

AU - Leslie, Lori A.

AU - Wei, Catherine

AU - Kim, Seo Hyun

AU - Naik, Seema

AU - Sundaram, Suchitra

AU - Reddy, Nishitha

AU - Farooq, Umar

AU - Kenkre, Vaishalee P.

AU - Epperla, Narendranath

AU - Blum, Kristie A.

AU - Khan, Nadia

AU - Singh, Daulath

AU - Alderuccio, Juan P.

AU - Godara, Amandeep

AU - Yazdy, Maryam Sarraf

AU - Diefenbach, Catherine

AU - Rabinovich, Emma

AU - Varma, Gaurav

AU - Karmali, Reem

AU - Shao, Yusra

AU - Trabolsi, Asaad

AU - Burkart, Madelyn

AU - Martin, Peter

AU - Stettner, Sarah

AU - Chauhan, Ayushi

AU - Choi, Yun Kyong

AU - Straker-Edwards, Allandria

AU - Klein, Andreas

AU - Churnetski, Michael C.

AU - Boughan, Kirsten M.

AU - Berg, Stephanie

AU - Haverkos, Bradley M.

AU - Orellana-Noia, Victor M.

AU - D'Angelo, Christopher

AU - Bond, David A.

AU - Maliske, Seth M.

AU - Vaca, Ryan

AU - Magarelli, Gabriella

AU - Sperling, Amy

AU - Gordon, Max J.

AU - David, Kevin A.

AU - Savani, Malvi

AU - Caimi, Paolo

AU - Kamdar, Manali

AU - Lunning, Matthew A.

AU - Palmisiano, Neil

AU - Venugopal, Parameswaran

AU - Portell, Craig A.

AU - Bachanova, Veronika

AU - Phillips, Tycel

AU - Lossos, Izidore S.

AU - Olszewski, Adam J.

N1 - 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

PY - 2021/7

Y1 - 2021/7

N2 - Central nervous system (CNS) involvement in Burkitt lymphoma poses a major therapeutic challenge, and the relative ability of contemporary regimens to treat CNS involvement remains uncertain. We describe the prognostic significance of CNS involvement and the incidence of CNS recurrence/progression after contemporary immunochemotherapy using real-world clinicopathological data from adults with Burkitt lymphoma diagnosed between 2009 and 2018 in 30 institutions in the USA. We examined associations between baseline CNS involvement, patients' characteristics, complete response rates, and survival. We also examined risk factors for CNS recurrence. Of 641 patients (aged 18 to 88 years), 120 (19%) had CNS involvement. CNS involvement was independently associated with human immunodeficiency virus infection, poor performance status, involvement of ≥2 extranodal sites, and bone marrow involvement. Selection of the first-line treatment regimen was unaffected by CNS involvement (P=0.93). Patients with CNS disease had significantly lower rates of complete response (59% vs. 77% for patients with and without CNS involvement, respectively; P<0.001), worse 3-year progression-free survival (adjusted hazard ratio [aHR]=1.53, 95% confidence interval [95% 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%) and was significantly lower among patients receiving other regimens (CODOX-M/IVAC, 4%, or hyperCVAD/MA, 3%) compared with DA-EPOCH-R (13%; adjusted sub-distribution HR=4.38, 95% CI:, 2.16-8.87; P<0.001). Baseline CNS involvement in Burkitt lymphoma is relatively common and portends inferior prognosis independently of the first-line treatment regimen selected. In real-world practice, regimens including intravenous systemic agents with pronounced CNS penetrance 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 the DA-EPOCH-R regimen.

AB - Central nervous system (CNS) involvement in Burkitt lymphoma poses a major therapeutic challenge, and the relative ability of contemporary regimens to treat CNS involvement remains uncertain. We describe the prognostic significance of CNS involvement and the incidence of CNS recurrence/progression after contemporary immunochemotherapy using real-world clinicopathological data from adults with Burkitt lymphoma diagnosed between 2009 and 2018 in 30 institutions in the USA. We examined associations between baseline CNS involvement, patients' characteristics, complete response rates, and survival. We also examined risk factors for CNS recurrence. Of 641 patients (aged 18 to 88 years), 120 (19%) had CNS involvement. CNS involvement was independently associated with human immunodeficiency virus infection, poor performance status, involvement of ≥2 extranodal sites, and bone marrow involvement. Selection of the first-line treatment regimen was unaffected by CNS involvement (P=0.93). Patients with CNS disease had significantly lower rates of complete response (59% vs. 77% for patients with and without CNS involvement, respectively; P<0.001), worse 3-year progression-free survival (adjusted hazard ratio [aHR]=1.53, 95% confidence interval [95% 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%) and was significantly lower among patients receiving other regimens (CODOX-M/IVAC, 4%, or hyperCVAD/MA, 3%) compared with DA-EPOCH-R (13%; adjusted sub-distribution HR=4.38, 95% CI:, 2.16-8.87; P<0.001). Baseline CNS involvement in Burkitt lymphoma is relatively common and portends inferior prognosis independently of the first-line treatment regimen selected. In real-world practice, regimens including intravenous systemic agents with pronounced CNS penetrance 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 the DA-EPOCH-R regimen.

UR - http://www.scopus.com/inward/record.url?scp=85111174760&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85111174760&partnerID=8YFLogxK

U2 - 10.3324/haematol.2020.270876

DO - 10.3324/haematol.2020.270876

M3 - Article

C2 - 33538152

AN - SCOPUS:85111174760

SN - 0390-6078

VL - 106

SP - 1932

EP - 1942

JO - Haematologica

JF - Haematologica

IS - 7

ER -

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

Abstract

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this