Combining brentuximab vedotin with dexamethasone, high-dose cytarabine and cisplatin as salvage treatment in relapsed or refractory Hodgkin lymphoma: the phase II HOVON/LLPC Transplant BRaVE study

Marie José Kersten; Julia Driessen; Josée M. Zijlstra; Wouter J. Plattel; Franck Morschhauser; Elly Lugtenburg; Pauline Brice; Martin Hutchings; Thomas Gastinne; Roberto D. Liu; Coreline N. Burggraaff; Marcel Nijland; Sanne H. Tonino; A. I.J. Arens; Roelf Valkema; Harm van Tinteren; Marta Lopez Yurda; Arjan Diepstra; Daphne de Jong; A (Anton) Hagenbeek

doi:10.3324/haematol.2019.243238

Combining brentuximab vedotin with dexamethasone, high-dose cytarabine and cisplatin as salvage treatment in relapsed or refractory Hodgkin lymphoma: the phase II HOVON/LLPC Transplant BRaVE study

Marie José Kersten^*, Julia Driessen, Josée M. Zijlstra, Wouter J. Plattel, Franck Morschhauser, Elly Lugtenburg, Pauline Brice, Martin Hutchings, Thomas Gastinne, Roberto D. Liu, Coreline N. Burggraaff, Marcel Nijland, Sanne H. Tonino, A. I.J. Arens, Roelf Valkema, Harm van Tinteren, Marta Lopez Yurda, Arjan Diepstra, Daphne de Jong, A (Anton) Hagenbeek

^*Corresponding author for this work

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

Abstract

Achieving a metabolic complete response (mCR) before high-dose chemotherapy (HDC) and autologous peripheral blood stem cell transplant (auto-PBSCT) predicts progression-free survival (PFS) in relapsed/refractory classical Hodgkin lymphoma (R/R cHL). We added brentuximab vedotin (BV) to DHAP (dexamethasone, high-dose cytarabine, cisplatin) to improve the mCR rate. In a phase I dose-escalation part of the study in 12 patients, we showed that BV-DHAP is feasible. This phase II study included 55 R/R cHL patients (23 primary refractory). Treatment consisted of three 21-day cycles of BV 1.8 mg/kg on day 1, and DHAP (dexamethasone 40 mg days 1-4, cisplatin 100 mg/m² day 1 and cytarabine 2x2 g/m² day 2). Patients with a metabolic partial response (mPR) or mCR proceeded to HDC/auto-PBSCT. Based on independent central [¹⁸F] fluorodeoxyglucose (FDG) - positron emission tomography (PET) - computed tomography (CT) scan review, 42 of 52 evaluable patients (81% [95%CI: 67-90]) achieved an mCR before HDC/auto-PBSCT, five had an mPR and five had progressive disease (3 were not evaluable). After HDC/auto-PBSCT, four patients with an mPR converted to an mCR.
Two-year PFS was 74% [95%CI: 63-86] and overall survival 95% [95%CI: 90-100]. Toxicity was manageable and mainly consisted of grade 3/4 hematologic toxicity, fever, nephrotoxicity, ototoxicity (grade 1/2), and transiently elevated liver enzymes during BV-DHAP.
Eighteen patients developed new onset peripheral neuropathy (maximum grade 1/2); all recovered. In conclusion, BV-DHAP is a very effective salvage regimen in R/R cHL patients, but patients should be monitored closely for toxicity

Original language	English
Pages (from-to)	1129-1137
Journal	Haematologica
Volume	106
Issue number	4
Early online date	9 Apr 2021
DOIs	https://doi.org/10.3324/haematol.2019.243238
Publication status	Published - 2021

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Kersten, M. J., Driessen, J., Zijlstra, J. M., Plattel, W. J., Morschhauser, F., Lugtenburg, E., Brice, P., Hutchings, M., Gastinne, T., Liu, R. D., Burggraaff, C. N., Nijland, M., Tonino, S. H., Arens, A. I. J., Valkema, R., van Tinteren, H., Lopez Yurda, M., Diepstra, A., de Jong, D., & Hagenbeek, A. (2021). Combining brentuximab vedotin with dexamethasone, high-dose cytarabine and cisplatin as salvage treatment in relapsed or refractory Hodgkin lymphoma: the phase II HOVON/LLPC Transplant BRaVE study. Haematologica, 106(4), 1129-1137. https://doi.org/10.3324/haematol.2019.243238

@article{2e171189cfc341d194e175aa9c1f4c51,

title = "Combining brentuximab vedotin with dexamethasone, high-dose cytarabine and cisplatin as salvage treatment in relapsed or refractory Hodgkin lymphoma: the phase II HOVON/LLPC Transplant BRaVE study",

abstract = "Achieving a metabolic complete response (mCR) before high-dose chemotherapy (HDC) and autologous peripheral blood stem cell transplant (auto-PBSCT) predicts progression-free survival (PFS) in relapsed/refractory classical Hodgkin lymphoma (R/R cHL). We added brentuximab vedotin (BV) to DHAP (dexamethasone, high-dose cytarabine, cisplatin) to improve the mCR rate. In a phase I dose-escalation part of the study in 12 patients, we showed that BV-DHAP is feasible. This phase II study included 55 R/R cHL patients (23 primary refractory). Treatment consisted of three 21-day cycles of BV 1.8 mg/kg on day 1, and DHAP (dexamethasone 40 mg days 1-4, cisplatin 100 mg/m² day 1 and cytarabine 2x2 g/m² day 2). Patients with a metabolic partial response (mPR) or mCR proceeded to HDC/auto-PBSCT. Based on independent central [18F] fluorodeoxyglucose (FDG) - positron emission tomography (PET) - computed tomography (CT) scan review, 42 of 52 evaluable patients (81% [95%CI: 67-90]) achieved an mCR before HDC/auto-PBSCT, five had an mPR and five had progressive disease (3 were not evaluable). After HDC/auto-PBSCT, four patients with an mPR converted to an mCR. Two-year PFS was 74% [95%CI: 63-86] and overall survival 95% [95%CI: 90-100]. Toxicity was manageable and mainly consisted of grade 3/4 hematologic toxicity, fever, nephrotoxicity, ototoxicity (grade 1/2), and transiently elevated liver enzymes during BV-DHAP.Eighteen patients developed new onset peripheral neuropathy (maximum grade 1/2); all recovered. In conclusion, BV-DHAP is a very effective salvage regimen in R/R cHL patients, but patients should be monitored closely for toxicity",

author = "Kersten, {Marie Jos{\'e}} and Julia Driessen and Zijlstra, {Jos{\'e}e M.} and Plattel, {Wouter J.} and Franck Morschhauser and Elly Lugtenburg and Pauline Brice and Martin Hutchings and Thomas Gastinne and Liu, {Roberto D.} and Burggraaff, {Coreline N.} and Marcel Nijland and Tonino, {Sanne H.} and Arens, {A. I.J.} and Roelf Valkema and {van Tinteren}, Harm and {Lopez Yurda}, Marta and Arjan Diepstra and {de Jong}, Daphne and Hagenbeek, {A (Anton)}",

year = "2021",

doi = "10.3324/haematol.2019.243238",

language = "English",

volume = "106",

pages = "1129--1137",

journal = "Haematologica",

issn = "0390-6078",

publisher = "Ferrata Storti Foundation",

number = "4",

}

Kersten, MJ, Driessen, J, Zijlstra, JM, Plattel, WJ, Morschhauser, F, Lugtenburg, E, Brice, P, Hutchings, M, Gastinne, T, Liu, RD, Burggraaff, CN, Nijland, M, Tonino, SH, Arens, AIJ, Valkema, R, van Tinteren, H, Lopez Yurda, M, Diepstra, A, de Jong, D & Hagenbeek, A 2021, 'Combining brentuximab vedotin with dexamethasone, high-dose cytarabine and cisplatin as salvage treatment in relapsed or refractory Hodgkin lymphoma: the phase II HOVON/LLPC Transplant BRaVE study', Haematologica, vol. 106, no. 4, pp. 1129-1137. https://doi.org/10.3324/haematol.2019.243238

Combining brentuximab vedotin with dexamethasone, high-dose cytarabine and cisplatin as salvage treatment in relapsed or refractory Hodgkin lymphoma : the phase II HOVON/LLPC Transplant BRaVE study. / Kersten, Marie José; Driessen, Julia; Zijlstra, Josée M. et al.

In: Haematologica, Vol. 106, No. 4, 2021, p. 1129-1137.

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

TY - JOUR

T1 - Combining brentuximab vedotin with dexamethasone, high-dose cytarabine and cisplatin as salvage treatment in relapsed or refractory Hodgkin lymphoma

T2 - the phase II HOVON/LLPC Transplant BRaVE study

AU - Kersten, Marie José

AU - Driessen, Julia

AU - Zijlstra, Josée M.

AU - Plattel, Wouter J.

AU - Morschhauser, Franck

AU - Lugtenburg, Elly

AU - Brice, Pauline

AU - Hutchings, Martin

AU - Gastinne, Thomas

AU - Liu, Roberto D.

AU - Burggraaff, Coreline N.

AU - Nijland, Marcel

AU - Tonino, Sanne H.

AU - Arens, A. I.J.

AU - Valkema, Roelf

AU - van Tinteren, Harm

AU - Lopez Yurda, Marta

AU - Diepstra, Arjan

AU - de Jong, Daphne

AU - Hagenbeek, A (Anton)

PY - 2021

Y1 - 2021

N2 - Achieving a metabolic complete response (mCR) before high-dose chemotherapy (HDC) and autologous peripheral blood stem cell transplant (auto-PBSCT) predicts progression-free survival (PFS) in relapsed/refractory classical Hodgkin lymphoma (R/R cHL). We added brentuximab vedotin (BV) to DHAP (dexamethasone, high-dose cytarabine, cisplatin) to improve the mCR rate. In a phase I dose-escalation part of the study in 12 patients, we showed that BV-DHAP is feasible. This phase II study included 55 R/R cHL patients (23 primary refractory). Treatment consisted of three 21-day cycles of BV 1.8 mg/kg on day 1, and DHAP (dexamethasone 40 mg days 1-4, cisplatin 100 mg/m² day 1 and cytarabine 2x2 g/m² day 2). Patients with a metabolic partial response (mPR) or mCR proceeded to HDC/auto-PBSCT. Based on independent central [18F] fluorodeoxyglucose (FDG) - positron emission tomography (PET) - computed tomography (CT) scan review, 42 of 52 evaluable patients (81% [95%CI: 67-90]) achieved an mCR before HDC/auto-PBSCT, five had an mPR and five had progressive disease (3 were not evaluable). After HDC/auto-PBSCT, four patients with an mPR converted to an mCR. Two-year PFS was 74% [95%CI: 63-86] and overall survival 95% [95%CI: 90-100]. Toxicity was manageable and mainly consisted of grade 3/4 hematologic toxicity, fever, nephrotoxicity, ototoxicity (grade 1/2), and transiently elevated liver enzymes during BV-DHAP.Eighteen patients developed new onset peripheral neuropathy (maximum grade 1/2); all recovered. In conclusion, BV-DHAP is a very effective salvage regimen in R/R cHL patients, but patients should be monitored closely for toxicity

AB - Achieving a metabolic complete response (mCR) before high-dose chemotherapy (HDC) and autologous peripheral blood stem cell transplant (auto-PBSCT) predicts progression-free survival (PFS) in relapsed/refractory classical Hodgkin lymphoma (R/R cHL). We added brentuximab vedotin (BV) to DHAP (dexamethasone, high-dose cytarabine, cisplatin) to improve the mCR rate. In a phase I dose-escalation part of the study in 12 patients, we showed that BV-DHAP is feasible. This phase II study included 55 R/R cHL patients (23 primary refractory). Treatment consisted of three 21-day cycles of BV 1.8 mg/kg on day 1, and DHAP (dexamethasone 40 mg days 1-4, cisplatin 100 mg/m² day 1 and cytarabine 2x2 g/m² day 2). Patients with a metabolic partial response (mPR) or mCR proceeded to HDC/auto-PBSCT. Based on independent central [18F] fluorodeoxyglucose (FDG) - positron emission tomography (PET) - computed tomography (CT) scan review, 42 of 52 evaluable patients (81% [95%CI: 67-90]) achieved an mCR before HDC/auto-PBSCT, five had an mPR and five had progressive disease (3 were not evaluable). After HDC/auto-PBSCT, four patients with an mPR converted to an mCR. Two-year PFS was 74% [95%CI: 63-86] and overall survival 95% [95%CI: 90-100]. Toxicity was manageable and mainly consisted of grade 3/4 hematologic toxicity, fever, nephrotoxicity, ototoxicity (grade 1/2), and transiently elevated liver enzymes during BV-DHAP.Eighteen patients developed new onset peripheral neuropathy (maximum grade 1/2); all recovered. In conclusion, BV-DHAP is a very effective salvage regimen in R/R cHL patients, but patients should be monitored closely for toxicity

U2 - 10.3324/haematol.2019.243238

DO - 10.3324/haematol.2019.243238

M3 - Article

C2 - 32273476

VL - 106

SP - 1129

EP - 1137

JO - Haematologica

JF - Haematologica

SN - 0390-6078

IS - 4

ER -

Combining brentuximab vedotin with dexamethasone, high-dose cytarabine and cisplatin as salvage treatment in relapsed or refractory Hodgkin lymphoma: the phase II HOVON/LLPC Transplant BRaVE study

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