Yttrium-90-Ibritumomab Tiuxetan (Zevalin®) Radioimmunotherapy after Cytoreduction with ESHAP Chemotherapy in Patients with Relapsed Follicular Non-Hodgkin Lymphoma: Final Results of a Phase II Study

Soham D. Puvvada, José M. Guillén-Rodríguez, Jessica Yan, Lora Inclán, Kara Heard, Xavier I. Rivera, Faiz Anwer, Daruka Mahadevan, Jonathan H Schatz, Daniel O. Persky

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Radioimmunotherapy (RIT) is effective in treating relapsed/refractory follicular lymphoma (FL), with durable remissions in first-line consolidation. We hypothesized that RIT with ibritumomab tiuxetan (Zevalin®) would result in durable remissions by eliminating minimal residual disease after cytoreduction. Methods: Patients with FL received 2 cycles of ESHAP (etoposide, methylprednisolone, cytarabine, cisplatin) every 28 days, followed by Zevalin 4–6 weeks later if there was no disease progression and bone marrow biopsy showed < 25% involvement. Results: Twenty-eight patients were treated, with a median age of 61 years, median of 3 prior therapies, 49% high-risk disease (Follicular Lymphoma International Prognostic Index, FLIPI), and 39% progressive disease. Three patients did not receive Zevalin due to residual bone marrow involvement. The main toxicities were cytopenias, with 11% febrile neutropenia. The overall response rate (ORR) was 72%, with 45% achieving complete response. With a median follow-up of 73 months, 1-year progression-free survival (PFS) was 38%, and median PFS was 10 months, but median overall survival (OS) was not reached. Conclusion: The study did not reach its primary endpoint of a 1-year PFS of 67.3%. Reasons for this could include low accrual, high-risk disease, and inadequate debulking provided by 2 cycles of ESHAP. However, this protocol was associated with tolerable toxicity, high ORR, and high OS. Further studies would optimize debulking and focus on high-risk FL patients.

Original languageEnglish (US)
JournalOncology (Switzerland)
DOIs
StateAccepted/In press - Feb 22 2018

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Radioimmunotherapy
Follicular Lymphoma
Non-Hodgkin's Lymphoma
Disease-Free Survival
Drug Therapy
Bone Marrow
Febrile Neutropenia
Survival
Cytarabine
Methylprednisolone
Residual Neoplasm
Etoposide
Cisplatin
Disease Progression
Biopsy
ibritumomab tiuxetan

Keywords

  • CD20
  • Follicular lymphoma
  • Indolent non-Hodgkin lymphoma
  • Phase II trial
  • Relapsed/refractory lymphoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Yttrium-90-Ibritumomab Tiuxetan (Zevalin®) Radioimmunotherapy after Cytoreduction with ESHAP Chemotherapy in Patients with Relapsed Follicular Non-Hodgkin Lymphoma : Final Results of a Phase II Study. / Puvvada, Soham D.; Guillén-Rodríguez, José M.; Yan, Jessica; Inclán, Lora; Heard, Kara; Rivera, Xavier I.; Anwer, Faiz; Mahadevan, Daruka; Schatz, Jonathan H; Persky, Daniel O.

In: Oncology (Switzerland), 22.02.2018.

Research output: Contribution to journalArticle

Puvvada, Soham D. ; Guillén-Rodríguez, José M. ; Yan, Jessica ; Inclán, Lora ; Heard, Kara ; Rivera, Xavier I. ; Anwer, Faiz ; Mahadevan, Daruka ; Schatz, Jonathan H ; Persky, Daniel O. / Yttrium-90-Ibritumomab Tiuxetan (Zevalin®) Radioimmunotherapy after Cytoreduction with ESHAP Chemotherapy in Patients with Relapsed Follicular Non-Hodgkin Lymphoma : Final Results of a Phase II Study. In: Oncology (Switzerland). 2018.
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title = "Yttrium-90-Ibritumomab Tiuxetan (Zevalin{\circledR}) Radioimmunotherapy after Cytoreduction with ESHAP Chemotherapy in Patients with Relapsed Follicular Non-Hodgkin Lymphoma: Final Results of a Phase II Study",
abstract = "Background: Radioimmunotherapy (RIT) is effective in treating relapsed/refractory follicular lymphoma (FL), with durable remissions in first-line consolidation. We hypothesized that RIT with ibritumomab tiuxetan (Zevalin{\circledR}) would result in durable remissions by eliminating minimal residual disease after cytoreduction. Methods: Patients with FL received 2 cycles of ESHAP (etoposide, methylprednisolone, cytarabine, cisplatin) every 28 days, followed by Zevalin 4–6 weeks later if there was no disease progression and bone marrow biopsy showed < 25{\%} involvement. Results: Twenty-eight patients were treated, with a median age of 61 years, median of 3 prior therapies, 49{\%} high-risk disease (Follicular Lymphoma International Prognostic Index, FLIPI), and 39{\%} progressive disease. Three patients did not receive Zevalin due to residual bone marrow involvement. The main toxicities were cytopenias, with 11{\%} febrile neutropenia. The overall response rate (ORR) was 72{\%}, with 45{\%} achieving complete response. With a median follow-up of 73 months, 1-year progression-free survival (PFS) was 38{\%}, and median PFS was 10 months, but median overall survival (OS) was not reached. Conclusion: The study did not reach its primary endpoint of a 1-year PFS of 67.3{\%}. Reasons for this could include low accrual, high-risk disease, and inadequate debulking provided by 2 cycles of ESHAP. However, this protocol was associated with tolerable toxicity, high ORR, and high OS. Further studies would optimize debulking and focus on high-risk FL patients.",
keywords = "CD20, Follicular lymphoma, Indolent non-Hodgkin lymphoma, Phase II trial, Relapsed/refractory lymphoma",
author = "Puvvada, {Soham D.} and Guill{\'e}n-Rodr{\'i}guez, {Jos{\'e} M.} and Jessica Yan and Lora Incl{\'a}n and Kara Heard and Rivera, {Xavier I.} and Faiz Anwer and Daruka Mahadevan and Schatz, {Jonathan H} and Persky, {Daniel O.}",
year = "2018",
month = "2",
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language = "English (US)",
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issn = "0030-2414",
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T1 - Yttrium-90-Ibritumomab Tiuxetan (Zevalin®) Radioimmunotherapy after Cytoreduction with ESHAP Chemotherapy in Patients with Relapsed Follicular Non-Hodgkin Lymphoma

T2 - Final Results of a Phase II Study

AU - Puvvada, Soham D.

AU - Guillén-Rodríguez, José M.

AU - Yan, Jessica

AU - Inclán, Lora

AU - Heard, Kara

AU - Rivera, Xavier I.

AU - Anwer, Faiz

AU - Mahadevan, Daruka

AU - Schatz, Jonathan H

AU - Persky, Daniel O.

PY - 2018/2/22

Y1 - 2018/2/22

N2 - Background: Radioimmunotherapy (RIT) is effective in treating relapsed/refractory follicular lymphoma (FL), with durable remissions in first-line consolidation. We hypothesized that RIT with ibritumomab tiuxetan (Zevalin®) would result in durable remissions by eliminating minimal residual disease after cytoreduction. Methods: Patients with FL received 2 cycles of ESHAP (etoposide, methylprednisolone, cytarabine, cisplatin) every 28 days, followed by Zevalin 4–6 weeks later if there was no disease progression and bone marrow biopsy showed < 25% involvement. Results: Twenty-eight patients were treated, with a median age of 61 years, median of 3 prior therapies, 49% high-risk disease (Follicular Lymphoma International Prognostic Index, FLIPI), and 39% progressive disease. Three patients did not receive Zevalin due to residual bone marrow involvement. The main toxicities were cytopenias, with 11% febrile neutropenia. The overall response rate (ORR) was 72%, with 45% achieving complete response. With a median follow-up of 73 months, 1-year progression-free survival (PFS) was 38%, and median PFS was 10 months, but median overall survival (OS) was not reached. Conclusion: The study did not reach its primary endpoint of a 1-year PFS of 67.3%. Reasons for this could include low accrual, high-risk disease, and inadequate debulking provided by 2 cycles of ESHAP. However, this protocol was associated with tolerable toxicity, high ORR, and high OS. Further studies would optimize debulking and focus on high-risk FL patients.

AB - Background: Radioimmunotherapy (RIT) is effective in treating relapsed/refractory follicular lymphoma (FL), with durable remissions in first-line consolidation. We hypothesized that RIT with ibritumomab tiuxetan (Zevalin®) would result in durable remissions by eliminating minimal residual disease after cytoreduction. Methods: Patients with FL received 2 cycles of ESHAP (etoposide, methylprednisolone, cytarabine, cisplatin) every 28 days, followed by Zevalin 4–6 weeks later if there was no disease progression and bone marrow biopsy showed < 25% involvement. Results: Twenty-eight patients were treated, with a median age of 61 years, median of 3 prior therapies, 49% high-risk disease (Follicular Lymphoma International Prognostic Index, FLIPI), and 39% progressive disease. Three patients did not receive Zevalin due to residual bone marrow involvement. The main toxicities were cytopenias, with 11% febrile neutropenia. The overall response rate (ORR) was 72%, with 45% achieving complete response. With a median follow-up of 73 months, 1-year progression-free survival (PFS) was 38%, and median PFS was 10 months, but median overall survival (OS) was not reached. Conclusion: The study did not reach its primary endpoint of a 1-year PFS of 67.3%. Reasons for this could include low accrual, high-risk disease, and inadequate debulking provided by 2 cycles of ESHAP. However, this protocol was associated with tolerable toxicity, high ORR, and high OS. Further studies would optimize debulking and focus on high-risk FL patients.

KW - CD20

KW - Follicular lymphoma

KW - Indolent non-Hodgkin lymphoma

KW - Phase II trial

KW - Relapsed/refractory lymphoma

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U2 - 10.1159/000486788

DO - 10.1159/000486788

M3 - Article

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AN - SCOPUS:85042373242

JO - Oncology

JF - Oncology

SN - 0030-2414

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