Multicenter Phase II study of sequential brentuximab vedotin and doxorubicin, vinblastine, and dacarbazine chemotherapy for older patients with untreated classical hodgkin lymphoma

Andrew M. Evens, Ranjana H. Advani, Irene B. Helenowski, Borko D. Jovanovic, Jane N. Winter, Leo I. Gordon, Jane N. Winte, Leo I. Gordon, Sonali M. Smith, Michelle Fanale, Robert G Bociek, Andreas K. Klein, Paul A. Hamlin

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Abstract

Purpose To improve the curability of older patients with newly diagnosed Hodgkin lymphoma. Patients and Methods We conducted a multicenter phase II study that administered brentuximab vedotin (Bv) sequentially before and after standard doxorubicin, vinblastine, and dacarbazine (AVD) for untreated patients with Hodgkin lymphoma age 60 years or older. After two lead-in doses of single-agent Bv (1.8 mg/kg once every 3 weeks), patients received six cycles of AVD chemotherapy followed by four consolidative doses of Bv in responding patients. Results Patient characteristics included median age of 69 years (range, 60 to 88 years), 63% male,median Eastern Cooperative Oncology Group performance status 1, 81% stage III to IV disease, 60% International Prognostic Score 3 to 7, median Cumulative Illness Rating Scale-Geriatric comorbidity score of 7 (52% grade 3 to 4); and 12% had loss of instrumental activities of daily living at diagnosis. Thirty-seven (77%) of 48 patients completed six cycles of AVD, and 35 patients (73%) received at least one Bv consolidation. Overall response and complete remission rates after initial Bv lead-in dose were 18 (82%) of 22 and 8 (36%) of 22, respectively, and 40 (95%) of 42 and 34 (90%) of 42, respectively, after six cycles of AVD among 42 response-evaluable patients. Twenty (42%) of 48 patients experienced a grade 3 to 4 adverse event, most commonly neutropenia (44%), febrile neutropenia and pneumonia (8%), or diarrhea (6%); 33% had grade 2 peripheral neuropathy, which was reversible in amajority of patients. By intent-to-treat, the 2-year event-free survival, progression-free survival, and overall survival rates were 80%, 84%, and 93%, respectively. Furthermore, 2-year progression-free survival rates for patients with a Cumulative Illness Rating Scale-Geriatric comorbidity score of ≥ 10 versus <10 were 45% versus 100%, respectively (P <.001), and with baseline loss versus no loss of instrumental activities of daily living were 25% versus 94% (P <.001), respectively, the latter persisting on multivariable analyses. Conclusion Altogether, sequential Bv-AVD was well tolerated and was associated with robust outcomes. Furthermore, geriatric-based measures were strongly associated with patient survival.

Original languageEnglish (US)
Pages (from-to)3015-3022
Number of pages8
JournalJournal of Clinical Oncology
Volume36
Issue number30
DOIs
StatePublished - Oct 20 2018

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Dacarbazine
Vinblastine
Hodgkin Disease
Doxorubicin
Drug Therapy
Geriatrics
Disease-Free Survival
Activities of Daily Living
cAC10-vcMMAE
Comorbidity
Survival Rate
Febrile Neutropenia
Peripheral Nervous System Diseases
Neutropenia
Diarrhea
Pneumonia

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Multicenter Phase II study of sequential brentuximab vedotin and doxorubicin, vinblastine, and dacarbazine chemotherapy for older patients with untreated classical hodgkin lymphoma. / Evens, Andrew M.; Advani, Ranjana H.; Helenowski, Irene B.; Jovanovic, Borko D.; Winter, Jane N.; Gordon, Leo I.; Winte, Jane N.; Gordon, Leo I.; Smith, Sonali M.; Fanale, Michelle; Bociek, Robert G; Klein, Andreas K.; Hamlin, Paul A.

In: Journal of Clinical Oncology, Vol. 36, No. 30, 20.10.2018, p. 3015-3022.

Research output: Contribution to journalArticle

Evens, AM, Advani, RH, Helenowski, IB, Jovanovic, BD, Winter, JN, Gordon, LI, Winte, JN, Gordon, LI, Smith, SM, Fanale, M, Bociek, RG, Klein, AK & Hamlin, PA 2018, 'Multicenter Phase II study of sequential brentuximab vedotin and doxorubicin, vinblastine, and dacarbazine chemotherapy for older patients with untreated classical hodgkin lymphoma', Journal of Clinical Oncology, vol. 36, no. 30, pp. 3015-3022. https://doi.org/10.1200/JCO.2018.79.0139
Evens, Andrew M. ; Advani, Ranjana H. ; Helenowski, Irene B. ; Jovanovic, Borko D. ; Winter, Jane N. ; Gordon, Leo I. ; Winte, Jane N. ; Gordon, Leo I. ; Smith, Sonali M. ; Fanale, Michelle ; Bociek, Robert G ; Klein, Andreas K. ; Hamlin, Paul A. / Multicenter Phase II study of sequential brentuximab vedotin and doxorubicin, vinblastine, and dacarbazine chemotherapy for older patients with untreated classical hodgkin lymphoma. In: Journal of Clinical Oncology. 2018 ; Vol. 36, No. 30. pp. 3015-3022.
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title = "Multicenter Phase II study of sequential brentuximab vedotin and doxorubicin, vinblastine, and dacarbazine chemotherapy for older patients with untreated classical hodgkin lymphoma",
abstract = "Purpose To improve the curability of older patients with newly diagnosed Hodgkin lymphoma. Patients and Methods We conducted a multicenter phase II study that administered brentuximab vedotin (Bv) sequentially before and after standard doxorubicin, vinblastine, and dacarbazine (AVD) for untreated patients with Hodgkin lymphoma age 60 years or older. After two lead-in doses of single-agent Bv (1.8 mg/kg once every 3 weeks), patients received six cycles of AVD chemotherapy followed by four consolidative doses of Bv in responding patients. Results Patient characteristics included median age of 69 years (range, 60 to 88 years), 63{\%} male,median Eastern Cooperative Oncology Group performance status 1, 81{\%} stage III to IV disease, 60{\%} International Prognostic Score 3 to 7, median Cumulative Illness Rating Scale-Geriatric comorbidity score of 7 (52{\%} grade 3 to 4); and 12{\%} had loss of instrumental activities of daily living at diagnosis. Thirty-seven (77{\%}) of 48 patients completed six cycles of AVD, and 35 patients (73{\%}) received at least one Bv consolidation. Overall response and complete remission rates after initial Bv lead-in dose were 18 (82{\%}) of 22 and 8 (36{\%}) of 22, respectively, and 40 (95{\%}) of 42 and 34 (90{\%}) of 42, respectively, after six cycles of AVD among 42 response-evaluable patients. Twenty (42{\%}) of 48 patients experienced a grade 3 to 4 adverse event, most commonly neutropenia (44{\%}), febrile neutropenia and pneumonia (8{\%}), or diarrhea (6{\%}); 33{\%} had grade 2 peripheral neuropathy, which was reversible in amajority of patients. By intent-to-treat, the 2-year event-free survival, progression-free survival, and overall survival rates were 80{\%}, 84{\%}, and 93{\%}, respectively. Furthermore, 2-year progression-free survival rates for patients with a Cumulative Illness Rating Scale-Geriatric comorbidity score of ≥ 10 versus <10 were 45{\%} versus 100{\%}, respectively (P <.001), and with baseline loss versus no loss of instrumental activities of daily living were 25{\%} versus 94{\%} (P <.001), respectively, the latter persisting on multivariable analyses. Conclusion Altogether, sequential Bv-AVD was well tolerated and was associated with robust outcomes. Furthermore, geriatric-based measures were strongly associated with patient survival.",
author = "Evens, {Andrew M.} and Advani, {Ranjana H.} and Helenowski, {Irene B.} and Jovanovic, {Borko D.} and Winter, {Jane N.} and Gordon, {Leo I.} and Winte, {Jane N.} and Gordon, {Leo I.} and Smith, {Sonali M.} and Michelle Fanale and Bociek, {Robert G} and Klein, {Andreas K.} and Hamlin, {Paul A.}",
year = "2018",
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day = "20",
doi = "10.1200/JCO.2018.79.0139",
language = "English (US)",
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pages = "3015--3022",
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TY - JOUR

T1 - Multicenter Phase II study of sequential brentuximab vedotin and doxorubicin, vinblastine, and dacarbazine chemotherapy for older patients with untreated classical hodgkin lymphoma

AU - Evens, Andrew M.

AU - Advani, Ranjana H.

AU - Helenowski, Irene B.

AU - Jovanovic, Borko D.

AU - Winter, Jane N.

AU - Gordon, Leo I.

AU - Winte, Jane N.

AU - Gordon, Leo I.

AU - Smith, Sonali M.

AU - Fanale, Michelle

AU - Bociek, Robert G

AU - Klein, Andreas K.

AU - Hamlin, Paul A.

PY - 2018/10/20

Y1 - 2018/10/20

N2 - Purpose To improve the curability of older patients with newly diagnosed Hodgkin lymphoma. Patients and Methods We conducted a multicenter phase II study that administered brentuximab vedotin (Bv) sequentially before and after standard doxorubicin, vinblastine, and dacarbazine (AVD) for untreated patients with Hodgkin lymphoma age 60 years or older. After two lead-in doses of single-agent Bv (1.8 mg/kg once every 3 weeks), patients received six cycles of AVD chemotherapy followed by four consolidative doses of Bv in responding patients. Results Patient characteristics included median age of 69 years (range, 60 to 88 years), 63% male,median Eastern Cooperative Oncology Group performance status 1, 81% stage III to IV disease, 60% International Prognostic Score 3 to 7, median Cumulative Illness Rating Scale-Geriatric comorbidity score of 7 (52% grade 3 to 4); and 12% had loss of instrumental activities of daily living at diagnosis. Thirty-seven (77%) of 48 patients completed six cycles of AVD, and 35 patients (73%) received at least one Bv consolidation. Overall response and complete remission rates after initial Bv lead-in dose were 18 (82%) of 22 and 8 (36%) of 22, respectively, and 40 (95%) of 42 and 34 (90%) of 42, respectively, after six cycles of AVD among 42 response-evaluable patients. Twenty (42%) of 48 patients experienced a grade 3 to 4 adverse event, most commonly neutropenia (44%), febrile neutropenia and pneumonia (8%), or diarrhea (6%); 33% had grade 2 peripheral neuropathy, which was reversible in amajority of patients. By intent-to-treat, the 2-year event-free survival, progression-free survival, and overall survival rates were 80%, 84%, and 93%, respectively. Furthermore, 2-year progression-free survival rates for patients with a Cumulative Illness Rating Scale-Geriatric comorbidity score of ≥ 10 versus <10 were 45% versus 100%, respectively (P <.001), and with baseline loss versus no loss of instrumental activities of daily living were 25% versus 94% (P <.001), respectively, the latter persisting on multivariable analyses. Conclusion Altogether, sequential Bv-AVD was well tolerated and was associated with robust outcomes. Furthermore, geriatric-based measures were strongly associated with patient survival.

AB - Purpose To improve the curability of older patients with newly diagnosed Hodgkin lymphoma. Patients and Methods We conducted a multicenter phase II study that administered brentuximab vedotin (Bv) sequentially before and after standard doxorubicin, vinblastine, and dacarbazine (AVD) for untreated patients with Hodgkin lymphoma age 60 years or older. After two lead-in doses of single-agent Bv (1.8 mg/kg once every 3 weeks), patients received six cycles of AVD chemotherapy followed by four consolidative doses of Bv in responding patients. Results Patient characteristics included median age of 69 years (range, 60 to 88 years), 63% male,median Eastern Cooperative Oncology Group performance status 1, 81% stage III to IV disease, 60% International Prognostic Score 3 to 7, median Cumulative Illness Rating Scale-Geriatric comorbidity score of 7 (52% grade 3 to 4); and 12% had loss of instrumental activities of daily living at diagnosis. Thirty-seven (77%) of 48 patients completed six cycles of AVD, and 35 patients (73%) received at least one Bv consolidation. Overall response and complete remission rates after initial Bv lead-in dose were 18 (82%) of 22 and 8 (36%) of 22, respectively, and 40 (95%) of 42 and 34 (90%) of 42, respectively, after six cycles of AVD among 42 response-evaluable patients. Twenty (42%) of 48 patients experienced a grade 3 to 4 adverse event, most commonly neutropenia (44%), febrile neutropenia and pneumonia (8%), or diarrhea (6%); 33% had grade 2 peripheral neuropathy, which was reversible in amajority of patients. By intent-to-treat, the 2-year event-free survival, progression-free survival, and overall survival rates were 80%, 84%, and 93%, respectively. Furthermore, 2-year progression-free survival rates for patients with a Cumulative Illness Rating Scale-Geriatric comorbidity score of ≥ 10 versus <10 were 45% versus 100%, respectively (P <.001), and with baseline loss versus no loss of instrumental activities of daily living were 25% versus 94% (P <.001), respectively, the latter persisting on multivariable analyses. Conclusion Altogether, sequential Bv-AVD was well tolerated and was associated with robust outcomes. Furthermore, geriatric-based measures were strongly associated with patient survival.

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