Single-route CNS prophylaxis for aggressive non-Hodgkin lymphomas: real-world outcomes from 21 US academic institutions

Victor Manuel Orellana-Noia; Daniel R. Reed; Ashley Alesia McCook; Jeremy Michael Sen; Christian M. Barlow; Mary Kate Malecek; Marcus Watkins; Brad S. Kahl; Michael A. Spinner; Ranjana Advani; Timothy J. Voorhees; Anson Snow; Natalie Sophia Grover; Amy Ayers; Jason Romancik; Yuxin Liu; Scott F. Huntington; Julio C. Chavez; Hayder Saeed; Aleksandr Lazaryan; Vikram Raghunathan; Stephen E. Spurgeon; Thomas A. Ollila; Christopher Del Prete; Adam Olszewski; Emily C. Ayers; Daniel J. Landsburg; Benjamin Echalier; Jun Lee; Manali Kamdar; Paolo F. Caimi; Timothy Fu; Jieqi Liu; Kevin A. David; Hanan Alharthy; Jennie Law; Reem Karmali; Harsh Shah; Deborah M. Stephens; Ajay Major; Alexandra E. Rojek; Sonali M. Smith; Amulya Yellala; Avyakta Kallam; Shazi Nakhoda; Nadia Khan; Mohammad Ahsan Sohail; Brian T. Hill; Odeth Barrett-Campbell; Frederick Lansigan; Jeffrey Switchenko; Jonathon Cohen; Craig A. Portell

doi:10.1182/blood.2021012888

Single-route CNS prophylaxis for aggressive non-Hodgkin lymphomas: real-world outcomes from 21 US academic institutions

Victor Manuel Orellana-Noia, Daniel R. Reed, Ashley Alesia McCook, Jeremy Michael Sen, Christian M. Barlow, Mary Kate Malecek, Marcus Watkins, Brad S. Kahl, Michael A. Spinner, Ranjana Advani, Timothy J. Voorhees, Anson Snow, Natalie Sophia Grover, Amy Ayers, Jason Romancik, Yuxin Liu, Scott F. Huntington, Julio C. Chavez, Hayder Saeed, Aleksandr LazaryanVikram Raghunathan, Stephen E. Spurgeon, Thomas A. Ollila, Christopher Del Prete, Adam Olszewski, Emily C. Ayers, Daniel J. Landsburg, Benjamin Echalier, Jun Lee, Manali Kamdar, Paolo F. Caimi, Timothy Fu, Jieqi Liu, Kevin A. David, Hanan Alharthy, Jennie Law, Reem Karmali, Harsh Shah, Deborah M. Stephens, Ajay Major, Alexandra E. Rojek, Sonali M. Smith, Amulya Yellala, Avyakta Kallam, Shazi Nakhoda, Nadia Khan, Mohammad Ahsan Sohail, Brian T. Hill, Odeth Barrett-Campbell, Frederick Lansigan, Jeffrey Switchenko, Jonathon Cohen, Craig A. Portell

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

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Abstract

Prophylaxis is commonly used to prevent central nervous sy stem (CNS) relapse in diffuse large B-cell lymphoma (DLBCL), with no clear standard of care. We retrospectively evaluated 1162 adult patients across 21 US academic centers with DLBCL or similar histologies who received single-route CNS prophylaxis as part of frontline therapy between 2013 and 2019. Prophylaxis was administered intrathecally(IT) in 894 (77%) and using systemic high-dose methotrexate (HD-MTX) in 236 (20%); 32 patients (3%) switched route due to toxicity and were assessed separately. By CNS-International Prognostic Index (IPI), 18% were considered low-risk, 51% moderate, and 30% high. Double-hit lymphoma (DHL) was confirmed in 243 of 866 evaluable patients (21%). Sixty-four patients (5.7%) had CNS relapse after median 7.1 months from diagnosis, including 15 of 64 (23%) within the first 6 months. There was no significant difference in CNS relapse between IT and HD-MTX recipients (5.4% vs 6.8%, P = .4), including after propensity score matching to account for differences between respective recipient groups. Weighting by CNS-IPI, expected vs observed CNS relapse rates were nearly identical (5.8% vs 5.7%). Testicular involvement was associated with high risk of CNS relapse (11.3%) despite most having lower CNS-IPI scores. DHL did not significantly predict for CNS relapse after single-route prophylaxis, including with adjustment for treatment regimen and other factors. This large study of CNS prophylaxis recipients with DLBCL found no significant difference in CNS relapse rates between routes of administration. Relapse rates among high-risk subgroups remain elevated, and reconsideration of prophylaxis strategies in DLBCL is of critical need.

Original language	English (US)
Pages (from-to)	413-423
Number of pages	11
Journal	Blood
Volume	139
Issue number	3
DOIs	https://doi.org/10.1182/blood.2021012888
State	Published - Jan 20 2022

ASJC Scopus subject areas

Biochemistry
Immunology
Hematology
Cell Biology

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10.1182/blood.2021012888

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Orellana-Noia, V. M., Reed, D. R., McCook, A. A., Sen, J. M., Barlow, C. M., Malecek, M. K., Watkins, M., Kahl, B. S., Spinner, M. A., Advani, R., Voorhees, T. J., Snow, A., Grover, N. S., Ayers, A., Romancik, J., Liu, Y., Huntington, S. F., Chavez, J. C., Saeed, H., ... Portell, C. A. (2022). Single-route CNS prophylaxis for aggressive non-Hodgkin lymphomas: real-world outcomes from 21 US academic institutions. Blood, 139(3), 413-423. https://doi.org/10.1182/blood.2021012888

Orellana-Noia, VM, Reed, DR, McCook, AA, Sen, JM, Barlow, CM, Malecek, MK, Watkins, M, Kahl, BS, Spinner, MA, Advani, R, Voorhees, TJ, Snow, A, Grover, NS, Ayers, A, Romancik, J, Liu, Y, Huntington, SF, Chavez, JC, Saeed, H, Lazaryan, A, Raghunathan, V, Spurgeon, SE, Ollila, TA, Del Prete, C, Olszewski, A, Ayers, EC, Landsburg, DJ, Echalier, B, Lee, J, Kamdar, M, Caimi, PF, Fu, T, Liu, J, David, KA, Alharthy, H, Law, J, Karmali, R, Shah, H, Stephens, DM, Major, A, Rojek, AE, Smith, SM, Yellala, A, Kallam, A, Nakhoda, S, Khan, N, Sohail, MA, Hill, BT, Barrett-Campbell, O, Lansigan, F, Switchenko, J, Cohen, J & Portell, CA 2022, 'Single-route CNS prophylaxis for aggressive non-Hodgkin lymphomas: real-world outcomes from 21 US academic institutions', Blood, vol. 139, no. 3, pp. 413-423. https://doi.org/10.1182/blood.2021012888

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title = "Single-route CNS prophylaxis for aggressive non-Hodgkin lymphomas: real-world outcomes from 21 US academic institutions",

abstract = "Prophylaxis is commonly used to prevent central nervous sy stem (CNS) relapse in diffuse large B-cell lymphoma (DLBCL), with no clear standard of care. We retrospectively evaluated 1162 adult patients across 21 US academic centers with DLBCL or similar histologies who received single-route CNS prophylaxis as part of frontline therapy between 2013 and 2019. Prophylaxis was administered intrathecally(IT) in 894 (77%) and using systemic high-dose methotrexate (HD-MTX) in 236 (20%); 32 patients (3%) switched route due to toxicity and were assessed separately. By CNS-International Prognostic Index (IPI), 18% were considered low-risk, 51% moderate, and 30% high. Double-hit lymphoma (DHL) was confirmed in 243 of 866 evaluable patients (21%). Sixty-four patients (5.7%) had CNS relapse after median 7.1 months from diagnosis, including 15 of 64 (23%) within the first 6 months. There was no significant difference in CNS relapse between IT and HD-MTX recipients (5.4% vs 6.8%, P = .4), including after propensity score matching to account for differences between respective recipient groups. Weighting by CNS-IPI, expected vs observed CNS relapse rates were nearly identical (5.8% vs 5.7%). Testicular involvement was associated with high risk of CNS relapse (11.3%) despite most having lower CNS-IPI scores. DHL did not significantly predict for CNS relapse after single-route prophylaxis, including with adjustment for treatment regimen and other factors. This large study of CNS prophylaxis recipients with DLBCL found no significant difference in CNS relapse rates between routes of administration. Relapse rates among high-risk subgroups remain elevated, and reconsideration of prophylaxis strategies in DLBCL is of critical need.",

author = "Orellana-Noia, {Victor Manuel} and Reed, {Daniel R.} and McCook, {Ashley Alesia} and Sen, {Jeremy Michael} and Barlow, {Christian M.} and Malecek, {Mary Kate} and Marcus Watkins and Kahl, {Brad S.} and Spinner, {Michael A.} and Ranjana Advani and Voorhees, {Timothy J.} and Anson Snow and Grover, {Natalie Sophia} and Amy Ayers and Jason Romancik and Yuxin Liu and Huntington, {Scott F.} and Chavez, {Julio C.} and Hayder Saeed and Aleksandr Lazaryan and Vikram Raghunathan and Spurgeon, {Stephen E.} and Ollila, {Thomas A.} and {Del Prete}, Christopher and Adam Olszewski and Ayers, {Emily C.} and Landsburg, {Daniel J.} and Benjamin Echalier and Jun Lee and Manali Kamdar and Caimi, {Paolo F.} and Timothy Fu and Jieqi Liu and David, {Kevin A.} and Hanan Alharthy and Jennie Law and Reem Karmali and Harsh Shah and Stephens, {Deborah M.} and Ajay Major and Rojek, {Alexandra E.} and Smith, {Sonali M.} and Amulya Yellala and Avyakta Kallam and Shazi Nakhoda and Nadia Khan and Sohail, {Mohammad Ahsan} and Hill, {Brian T.} and Odeth Barrett-Campbell and Frederick Lansigan and Jeffrey Switchenko and Jonathon Cohen and Portell, {Craig A.}",

note = "Publisher Copyright: {\textcopyright} 2022 American Society of Hematology",

year = "2022",

month = jan,

day = "20",

doi = "10.1182/blood.2021012888",

language = "English (US)",

volume = "139",

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T1 - Single-route CNS prophylaxis for aggressive non-Hodgkin lymphomas

T2 - real-world outcomes from 21 US academic institutions

AU - Orellana-Noia, Victor Manuel

AU - Reed, Daniel R.

AU - McCook, Ashley Alesia

AU - Sen, Jeremy Michael

AU - Barlow, Christian M.

AU - Malecek, Mary Kate

AU - Watkins, Marcus

AU - Kahl, Brad S.

AU - Spinner, Michael A.

AU - Advani, Ranjana

AU - Voorhees, Timothy J.

AU - Snow, Anson

AU - Grover, Natalie Sophia

AU - Ayers, Amy

AU - Romancik, Jason

AU - Liu, Yuxin

AU - Huntington, Scott F.

AU - Chavez, Julio C.

AU - Saeed, Hayder

AU - Lazaryan, Aleksandr

AU - Raghunathan, Vikram

AU - Spurgeon, Stephen E.

AU - Ollila, Thomas A.

AU - Del Prete, Christopher

AU - Olszewski, Adam

AU - Ayers, Emily C.

AU - Landsburg, Daniel J.

AU - Echalier, Benjamin

AU - Lee, Jun

AU - Kamdar, Manali

AU - Caimi, Paolo F.

AU - Fu, Timothy

AU - Liu, Jieqi

AU - David, Kevin A.

AU - Alharthy, Hanan

AU - Law, Jennie

AU - Karmali, Reem

AU - Shah, Harsh

AU - Stephens, Deborah M.

AU - Major, Ajay

AU - Rojek, Alexandra E.

AU - Smith, Sonali M.

AU - Yellala, Amulya

AU - Kallam, Avyakta

AU - Nakhoda, Shazi

AU - Khan, Nadia

AU - Sohail, Mohammad Ahsan

AU - Hill, Brian T.

AU - Barrett-Campbell, Odeth

AU - Lansigan, Frederick

AU - Switchenko, Jeffrey

AU - Cohen, Jonathon

AU - Portell, Craig A.

PY - 2022/1/20

Y1 - 2022/1/20

N2 - Prophylaxis is commonly used to prevent central nervous sy stem (CNS) relapse in diffuse large B-cell lymphoma (DLBCL), with no clear standard of care. We retrospectively evaluated 1162 adult patients across 21 US academic centers with DLBCL or similar histologies who received single-route CNS prophylaxis as part of frontline therapy between 2013 and 2019. Prophylaxis was administered intrathecally(IT) in 894 (77%) and using systemic high-dose methotrexate (HD-MTX) in 236 (20%); 32 patients (3%) switched route due to toxicity and were assessed separately. By CNS-International Prognostic Index (IPI), 18% were considered low-risk, 51% moderate, and 30% high. Double-hit lymphoma (DHL) was confirmed in 243 of 866 evaluable patients (21%). Sixty-four patients (5.7%) had CNS relapse after median 7.1 months from diagnosis, including 15 of 64 (23%) within the first 6 months. There was no significant difference in CNS relapse between IT and HD-MTX recipients (5.4% vs 6.8%, P = .4), including after propensity score matching to account for differences between respective recipient groups. Weighting by CNS-IPI, expected vs observed CNS relapse rates were nearly identical (5.8% vs 5.7%). Testicular involvement was associated with high risk of CNS relapse (11.3%) despite most having lower CNS-IPI scores. DHL did not significantly predict for CNS relapse after single-route prophylaxis, including with adjustment for treatment regimen and other factors. This large study of CNS prophylaxis recipients with DLBCL found no significant difference in CNS relapse rates between routes of administration. Relapse rates among high-risk subgroups remain elevated, and reconsideration of prophylaxis strategies in DLBCL is of critical need.

AB - Prophylaxis is commonly used to prevent central nervous sy stem (CNS) relapse in diffuse large B-cell lymphoma (DLBCL), with no clear standard of care. We retrospectively evaluated 1162 adult patients across 21 US academic centers with DLBCL or similar histologies who received single-route CNS prophylaxis as part of frontline therapy between 2013 and 2019. Prophylaxis was administered intrathecally(IT) in 894 (77%) and using systemic high-dose methotrexate (HD-MTX) in 236 (20%); 32 patients (3%) switched route due to toxicity and were assessed separately. By CNS-International Prognostic Index (IPI), 18% were considered low-risk, 51% moderate, and 30% high. Double-hit lymphoma (DHL) was confirmed in 243 of 866 evaluable patients (21%). Sixty-four patients (5.7%) had CNS relapse after median 7.1 months from diagnosis, including 15 of 64 (23%) within the first 6 months. There was no significant difference in CNS relapse between IT and HD-MTX recipients (5.4% vs 6.8%, P = .4), including after propensity score matching to account for differences between respective recipient groups. Weighting by CNS-IPI, expected vs observed CNS relapse rates were nearly identical (5.8% vs 5.7%). Testicular involvement was associated with high risk of CNS relapse (11.3%) despite most having lower CNS-IPI scores. DHL did not significantly predict for CNS relapse after single-route prophylaxis, including with adjustment for treatment regimen and other factors. This large study of CNS prophylaxis recipients with DLBCL found no significant difference in CNS relapse rates between routes of administration. Relapse rates among high-risk subgroups remain elevated, and reconsideration of prophylaxis strategies in DLBCL is of critical need.

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Single-route CNS prophylaxis for aggressive non-Hodgkin lymphomas: real-world outcomes from 21 US academic institutions

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