Brentuximab vedotin, nivolumab, doxorubicin, and dacarbazine for advanced-stage classical Hodgkin lymphoma

Hun Ju Lee; Rod Ramchandren; Judah Friedman; Jason Melear; Ian W. Flinn; John M. Burke; Yuliya Linhares; Paul Gonzales; Matthew Peterson; Mihir Raval; Rangaswamy Chintapatla; Tatyana A. Feldman; Habte Yimer; Miguel Islas-Ohlmayer; Ameet Patel; Leland Metheny; Asad Dean; Vishal Rana; Mitul D. Gandhi; John Renshaw; Linda Ho; Michelle A. Fanale; Wenchuan Guo; Christopher A. Yasenchak

doi:10.1182/blood.2024024681

Brentuximab vedotin, nivolumab, doxorubicin, and dacarbazine for advanced-stage classical Hodgkin lymphoma

Hun Ju Lee, Rod Ramchandren, Judah Friedman, Jason Melear, Ian W. Flinn, John M. Burke, Yuliya Linhares, Paul Gonzales, Matthew Peterson, Mihir Raval, Rangaswamy Chintapatla, Tatyana A. Feldman, Habte Yimer, Miguel Islas-Ohlmayer, Ameet Patel, Leland Metheny, Asad Dean, Vishal Rana, Mitul D. Gandhi, John RenshawLinda Ho, Michelle A. Fanale, Wenchuan Guo, Christopher A. Yasenchak

School of Medicine

Hackensack Meridian School of Medicine

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

Abstract

Treatment options for stage I/II bulky and advanced-stage disease have recently extensively changed. For decades in North America, ABVD (doxorubicin hydrochloride [Adriamycin], bleomycin sulfate, vinblastine sulfate, and dacarbazine) has been a frontline standard-of-care option for patients with advanced classical Hodgkin lymphoma (cHL). Recent data on combining brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine demonstrated improved overall survival compared with ABVD but increased adverse events (AEs). We hypothesized that replacing vinblastine with nivolumab (brentuximab vedotin and nivolumab [AN] + doxorubicin and dacarbazine [AD]; AN+AD) may improve efficacy and safety. This phase 2, open-label multipart, multicenter study enrolled patients with treatment-naive stage II bulky or III/IV cHL. Patients received ≤6 cycles of AN+AD; granulocyte-colony stimulating factor (G-CSF) prophylaxis was optional, per institutional guidelines. At the time of planned analysis (N = 57), complete response (CR) and objective response rates were 88% (95% confidence interval [CI], 76.3-94.9) and 93% (95% CI, 83.0-98.1), respectively. With a median follow-up of 24.2 months (95% CI, 23.4-26.9), the 2-year progression-free survival rate was 88% (95% CI, 75.7-94.6); 88% (95% CI, 75.7-94.6) had a response lasting >2 years. Most common grade ≥3 treatment-related AEs were alanine aminotransferase increased (11%) and neutropenia (9%); 44% had treatment-related peripheral sensory neuropathy (grade 1/2, 40%; grade 3, 4%). No febrile neutropenia occurred; 49% received G-CSF prophylaxis. AN+AD led to a high CR rate and favorable safety profile. Further evaluation of programmed death receptor 1 inhibitor and CD30 antibody–drug conjugate combination regimens in frontline advanced-stage cHL is warranted. This trial was registered at www.clinicaltrials.gov as #NCT03646123 and www.clinicaltrialsregister.eu as #EudraCT 2020-004027-17.

Original language	English
Pages (from-to)	290-299
Number of pages	10
Journal	Blood
Volume	145
Issue number	3
DOIs	https://doi.org/10.1182/blood.2024024681
State	Published - Jan 16 2025

ASJC Scopus subject areas

Biochemistry
Immunology
Hematology
Cell Biology

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10.1182/blood.2024024681

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Lee, H. J., Ramchandren, R., Friedman, J., Melear, J., Flinn, I. W., Burke, J. M., Linhares, Y., Gonzales, P., Peterson, M., Raval, M., Chintapatla, R., Feldman, T. A., Yimer, H., Islas-Ohlmayer, M., Patel, A., Metheny, L., Dean, A., Rana, V., Gandhi, M. D., ... Yasenchak, C. A. (2025). Brentuximab vedotin, nivolumab, doxorubicin, and dacarbazine for advanced-stage classical Hodgkin lymphoma. Blood, 145(3), 290-299. https://doi.org/10.1182/blood.2024024681

@article{43b01ae32e274400bce7dba2cb4fd9b6,

title = "Brentuximab vedotin, nivolumab, doxorubicin, and dacarbazine for advanced-stage classical Hodgkin lymphoma",

abstract = "Treatment options for stage I/II bulky and advanced-stage disease have recently extensively changed. For decades in North America, ABVD (doxorubicin hydrochloride [Adriamycin], bleomycin sulfate, vinblastine sulfate, and dacarbazine) has been a frontline standard-of-care option for patients with advanced classical Hodgkin lymphoma (cHL). Recent data on combining brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine demonstrated improved overall survival compared with ABVD but increased adverse events (AEs). We hypothesized that replacing vinblastine with nivolumab (brentuximab vedotin and nivolumab [AN] + doxorubicin and dacarbazine [AD]; AN+AD) may improve efficacy and safety. This phase 2, open-label multipart, multicenter study enrolled patients with treatment-naive stage II bulky or III/IV cHL. Patients received ≤6 cycles of AN+AD; granulocyte-colony stimulating factor (G-CSF) prophylaxis was optional, per institutional guidelines. At the time of planned analysis (N = 57), complete response (CR) and objective response rates were 88% (95% confidence interval [CI], 76.3-94.9) and 93% (95% CI, 83.0-98.1), respectively. With a median follow-up of 24.2 months (95% CI, 23.4-26.9), the 2-year progression-free survival rate was 88% (95% CI, 75.7-94.6); 88% (95% CI, 75.7-94.6) had a response lasting >2 years. Most common grade ≥3 treatment-related AEs were alanine aminotransferase increased (11%) and neutropenia (9%); 44% had treatment-related peripheral sensory neuropathy (grade 1/2, 40%; grade 3, 4%). No febrile neutropenia occurred; 49% received G-CSF prophylaxis. AN+AD led to a high CR rate and favorable safety profile. Further evaluation of programmed death receptor 1 inhibitor and CD30 antibody–drug conjugate combination regimens in frontline advanced-stage cHL is warranted. This trial was registered at www.clinicaltrials.gov as #NCT03646123 and www.clinicaltrialsregister.eu as #EudraCT 2020-004027-17.",

author = "Lee, {Hun Ju} and Rod Ramchandren and Judah Friedman and Jason Melear and Flinn, {Ian W.} and Burke, {John M.} and Yuliya Linhares and Paul Gonzales and Matthew Peterson and Mihir Raval and Rangaswamy Chintapatla and Feldman, {Tatyana A.} and Habte Yimer and Miguel Islas-Ohlmayer and Ameet Patel and Leland Metheny and Asad Dean and Vishal Rana and Gandhi, {Mitul D.} and John Renshaw and Linda Ho and Fanale, {Michelle A.} and Wenchuan Guo and Yasenchak, {Christopher A.}",

note = "Publisher Copyright: {\textcopyright} 2025",

year = "2025",

month = jan,

day = "16",

doi = "10.1182/blood.2024024681",

language = "English",

volume = "145",

pages = "290--299",

journal = "Blood",

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publisher = "Elsevier B.V.",

number = "3",

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Lee, HJ, Ramchandren, R, Friedman, J, Melear, J, Flinn, IW, Burke, JM, Linhares, Y, Gonzales, P, Peterson, M, Raval, M, Chintapatla, R, Feldman, TA, Yimer, H, Islas-Ohlmayer, M, Patel, A, Metheny, L, Dean, A, Rana, V, Gandhi, MD, Renshaw, J, Ho, L, Fanale, MA, Guo, W & Yasenchak, CA 2025, 'Brentuximab vedotin, nivolumab, doxorubicin, and dacarbazine for advanced-stage classical Hodgkin lymphoma', Blood, vol. 145, no. 3, pp. 290-299. https://doi.org/10.1182/blood.2024024681

TY - JOUR

T1 - Brentuximab vedotin, nivolumab, doxorubicin, and dacarbazine for advanced-stage classical Hodgkin lymphoma

AU - Lee, Hun Ju

AU - Ramchandren, Rod

AU - Friedman, Judah

AU - Melear, Jason

AU - Flinn, Ian W.

AU - Burke, John M.

AU - Linhares, Yuliya

AU - Gonzales, Paul

AU - Peterson, Matthew

AU - Raval, Mihir

AU - Chintapatla, Rangaswamy

AU - Feldman, Tatyana A.

AU - Yimer, Habte

AU - Islas-Ohlmayer, Miguel

AU - Patel, Ameet

AU - Metheny, Leland

AU - Dean, Asad

AU - Rana, Vishal

AU - Gandhi, Mitul D.

AU - Renshaw, John

AU - Ho, Linda

AU - Fanale, Michelle A.

AU - Guo, Wenchuan

AU - Yasenchak, Christopher A.

PY - 2025/1/16

Y1 - 2025/1/16

N2 - Treatment options for stage I/II bulky and advanced-stage disease have recently extensively changed. For decades in North America, ABVD (doxorubicin hydrochloride [Adriamycin], bleomycin sulfate, vinblastine sulfate, and dacarbazine) has been a frontline standard-of-care option for patients with advanced classical Hodgkin lymphoma (cHL). Recent data on combining brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine demonstrated improved overall survival compared with ABVD but increased adverse events (AEs). We hypothesized that replacing vinblastine with nivolumab (brentuximab vedotin and nivolumab [AN] + doxorubicin and dacarbazine [AD]; AN+AD) may improve efficacy and safety. This phase 2, open-label multipart, multicenter study enrolled patients with treatment-naive stage II bulky or III/IV cHL. Patients received ≤6 cycles of AN+AD; granulocyte-colony stimulating factor (G-CSF) prophylaxis was optional, per institutional guidelines. At the time of planned analysis (N = 57), complete response (CR) and objective response rates were 88% (95% confidence interval [CI], 76.3-94.9) and 93% (95% CI, 83.0-98.1), respectively. With a median follow-up of 24.2 months (95% CI, 23.4-26.9), the 2-year progression-free survival rate was 88% (95% CI, 75.7-94.6); 88% (95% CI, 75.7-94.6) had a response lasting >2 years. Most common grade ≥3 treatment-related AEs were alanine aminotransferase increased (11%) and neutropenia (9%); 44% had treatment-related peripheral sensory neuropathy (grade 1/2, 40%; grade 3, 4%). No febrile neutropenia occurred; 49% received G-CSF prophylaxis. AN+AD led to a high CR rate and favorable safety profile. Further evaluation of programmed death receptor 1 inhibitor and CD30 antibody–drug conjugate combination regimens in frontline advanced-stage cHL is warranted. This trial was registered at www.clinicaltrials.gov as #NCT03646123 and www.clinicaltrialsregister.eu as #EudraCT 2020-004027-17.

AB - Treatment options for stage I/II bulky and advanced-stage disease have recently extensively changed. For decades in North America, ABVD (doxorubicin hydrochloride [Adriamycin], bleomycin sulfate, vinblastine sulfate, and dacarbazine) has been a frontline standard-of-care option for patients with advanced classical Hodgkin lymphoma (cHL). Recent data on combining brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine demonstrated improved overall survival compared with ABVD but increased adverse events (AEs). We hypothesized that replacing vinblastine with nivolumab (brentuximab vedotin and nivolumab [AN] + doxorubicin and dacarbazine [AD]; AN+AD) may improve efficacy and safety. This phase 2, open-label multipart, multicenter study enrolled patients with treatment-naive stage II bulky or III/IV cHL. Patients received ≤6 cycles of AN+AD; granulocyte-colony stimulating factor (G-CSF) prophylaxis was optional, per institutional guidelines. At the time of planned analysis (N = 57), complete response (CR) and objective response rates were 88% (95% confidence interval [CI], 76.3-94.9) and 93% (95% CI, 83.0-98.1), respectively. With a median follow-up of 24.2 months (95% CI, 23.4-26.9), the 2-year progression-free survival rate was 88% (95% CI, 75.7-94.6); 88% (95% CI, 75.7-94.6) had a response lasting >2 years. Most common grade ≥3 treatment-related AEs were alanine aminotransferase increased (11%) and neutropenia (9%); 44% had treatment-related peripheral sensory neuropathy (grade 1/2, 40%; grade 3, 4%). No febrile neutropenia occurred; 49% received G-CSF prophylaxis. AN+AD led to a high CR rate and favorable safety profile. Further evaluation of programmed death receptor 1 inhibitor and CD30 antibody–drug conjugate combination regimens in frontline advanced-stage cHL is warranted. This trial was registered at www.clinicaltrials.gov as #NCT03646123 and www.clinicaltrialsregister.eu as #EudraCT 2020-004027-17.

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U2 - 10.1182/blood.2024024681

DO - 10.1182/blood.2024024681

M3 - Article

C2 - 39622165

SN - 0006-4971

VL - 145

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JO - Blood

JF - Blood

IS - 3

ER -

Brentuximab vedotin, nivolumab, doxorubicin, and dacarbazine for advanced-stage classical Hodgkin lymphoma

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