Interim results of brentuximab vedotin in combination with nivolumab in patients with relapsed or refractory Hodgkin lymphoma

Alex F. Herrera, Alison J. Moskowitz, Nancy L. Bartlett, Julie M. Vose, Radhakrishnan Ramchandren, Tatyana A. Feldman, Ann S. LaCasce, Stephen Maxted Ansell, Craig H. Moskowitz, Keenan Fenton, Carol Anne Ogden, David Taft, Qu Zhang, Kazunobu Kato, Mary Campbell, Ranjana H. Advani

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Abstract

In this phase 1/2 study, brentuximab vedotin (BV) and nivolumab (Nivo) administered in combination were evaluated as initial salvage therapy in patients with relapsed or refractory (R/R) classical Hodgkin lymphoma (HL). Patients received up to 4 cycles of combination treatment, with BV administered on day 1 and Nivo on day 8 of the first cycle. For cycles 2 to 4, BV and Nivo were both administered on day 1. After study treatment, responses were evaluated by investigators per the 2014 Lugano classification, and patients could proceed to autologous stem cell transplantation (ASCT). Sixty-two patients were enrolled; the complete response rate among all treated patients (n 5 61) was 61%, with an objective response rate of 82%. Before ASCT, adverse events (AEs) occurred in 98% of patients, mostly grades 1 and 2. Infusion-related reactions (IRRs) occurred in 44% of patients overall, with 41% of patients experiencing an IRR during at least 1 infusion of BV. Five patients (8%) were treated with systemic steroids for immune-related AEs. A reduction of peripheral T-cell subsets including regulatory T cells was observed after the first dose of BV, and reduced serum levels of thymus- and activation-regulated chemokine concurrent with an increase in proinflammatory cytokines and chemokines were seen after the first BV plus Nivo infusions. The combination of BV plus Nivo was an active and well-tolerated first salvage regimen, potentially providing patients with R/R HL an alternative to traditional chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT02572167.

Original languageEnglish (US)
Pages (from-to)1183-1194
Number of pages12
JournalBlood
Volume131
Issue number11
DOIs
StatePublished - Mar 15 2018

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Hodgkin Disease
Refractory materials
Salvaging
T-cells
Stem cells
Chemokine CCL17
Stem Cell Transplantation
Chemotherapy
cAC10-vcMMAE
nivolumab
Chemokines
Salvage Therapy
T-Lymphocyte Subsets
Steroids
Regulatory T-Lymphocytes
Cytokines
Research Personnel
Drug Therapy
Therapeutics
Serum

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Herrera, A. F., Moskowitz, A. J., Bartlett, N. L., Vose, J. M., Ramchandren, R., Feldman, T. A., ... Advani, R. H. (2018). Interim results of brentuximab vedotin in combination with nivolumab in patients with relapsed or refractory Hodgkin lymphoma. Blood, 131(11), 1183-1194. https://doi.org/10.1182/blood-2017-10-811224

Interim results of brentuximab vedotin in combination with nivolumab in patients with relapsed or refractory Hodgkin lymphoma. / Herrera, Alex F.; Moskowitz, Alison J.; Bartlett, Nancy L.; Vose, Julie M.; Ramchandren, Radhakrishnan; Feldman, Tatyana A.; LaCasce, Ann S.; Ansell, Stephen Maxted; Moskowitz, Craig H.; Fenton, Keenan; Ogden, Carol Anne; Taft, David; Zhang, Qu; Kato, Kazunobu; Campbell, Mary; Advani, Ranjana H.

In: Blood, Vol. 131, No. 11, 15.03.2018, p. 1183-1194.

Research output: Contribution to journalArticle

Herrera, AF, Moskowitz, AJ, Bartlett, NL, Vose, JM, Ramchandren, R, Feldman, TA, LaCasce, AS, Ansell, SM, Moskowitz, CH, Fenton, K, Ogden, CA, Taft, D, Zhang, Q, Kato, K, Campbell, M & Advani, RH 2018, 'Interim results of brentuximab vedotin in combination with nivolumab in patients with relapsed or refractory Hodgkin lymphoma', Blood, vol. 131, no. 11, pp. 1183-1194. https://doi.org/10.1182/blood-2017-10-811224
Herrera AF, Moskowitz AJ, Bartlett NL, Vose JM, Ramchandren R, Feldman TA et al. Interim results of brentuximab vedotin in combination with nivolumab in patients with relapsed or refractory Hodgkin lymphoma. Blood. 2018 Mar 15;131(11):1183-1194. https://doi.org/10.1182/blood-2017-10-811224
Herrera, Alex F. ; Moskowitz, Alison J. ; Bartlett, Nancy L. ; Vose, Julie M. ; Ramchandren, Radhakrishnan ; Feldman, Tatyana A. ; LaCasce, Ann S. ; Ansell, Stephen Maxted ; Moskowitz, Craig H. ; Fenton, Keenan ; Ogden, Carol Anne ; Taft, David ; Zhang, Qu ; Kato, Kazunobu ; Campbell, Mary ; Advani, Ranjana H. / Interim results of brentuximab vedotin in combination with nivolumab in patients with relapsed or refractory Hodgkin lymphoma. In: Blood. 2018 ; Vol. 131, No. 11. pp. 1183-1194.
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AU - Ramchandren, Radhakrishnan

AU - Feldman, Tatyana A.

AU - LaCasce, Ann S.

AU - Ansell, Stephen Maxted

AU - Moskowitz, Craig H.

AU - Fenton, Keenan

AU - Ogden, Carol Anne

AU - Taft, David

AU - Zhang, Qu

AU - Kato, Kazunobu

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AU - Advani, Ranjana H.

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N2 - In this phase 1/2 study, brentuximab vedotin (BV) and nivolumab (Nivo) administered in combination were evaluated as initial salvage therapy in patients with relapsed or refractory (R/R) classical Hodgkin lymphoma (HL). Patients received up to 4 cycles of combination treatment, with BV administered on day 1 and Nivo on day 8 of the first cycle. For cycles 2 to 4, BV and Nivo were both administered on day 1. After study treatment, responses were evaluated by investigators per the 2014 Lugano classification, and patients could proceed to autologous stem cell transplantation (ASCT). Sixty-two patients were enrolled; the complete response rate among all treated patients (n 5 61) was 61%, with an objective response rate of 82%. Before ASCT, adverse events (AEs) occurred in 98% of patients, mostly grades 1 and 2. Infusion-related reactions (IRRs) occurred in 44% of patients overall, with 41% of patients experiencing an IRR during at least 1 infusion of BV. Five patients (8%) were treated with systemic steroids for immune-related AEs. A reduction of peripheral T-cell subsets including regulatory T cells was observed after the first dose of BV, and reduced serum levels of thymus- and activation-regulated chemokine concurrent with an increase in proinflammatory cytokines and chemokines were seen after the first BV plus Nivo infusions. The combination of BV plus Nivo was an active and well-tolerated first salvage regimen, potentially providing patients with R/R HL an alternative to traditional chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT02572167.

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