Histomorphological responses after therapy with pegylated interferon α-2a in patients with essential thrombocythemia (ET) and polycythemia vera (PV)

Lucia Masarova, C. Cameron Yin, Jorge E. Cortes, Marina Konopleva, Gautam Borthakur, Kate J. Newberry, Hagop M. Kantarjian, Carlos E. Bueso-Ramos, Srdan Verstovsek

Research output: Contribution to journalArticle

Abstract

Background: Pegylated interferon alfa-2a (PEG-IFN-α-2a) is a potent immunomodulating agent capable of inducing high rate of hematologic and even complete molecular remission in patients with essential thrombocythemia (ET) and polycythemia vera (PV). We recently reported results of a phase 2 trial of PEG-IFN-α-2a in 83 patients with ET and PV after a median follow-up of 83 months. Here we report an analysis of bone marrow (BM) responses in these patients. Methods: Among 83 patients, 58 (70%, PV 25, ET 31) had evaluable BM samples. BM responses and fibrosis grading were defined according to the International Working Group for Myeloproliferative Neoplasms Research and Treatment, and the European Consensus on grading of BM fibrosis, respectively. BM was assessed prior to enrollment, and every 6-24 months while on therapy in all patients, and after therapy discontinuation in some patients. Results: The median age of analyzed 58 patients was 52 years, and 29% were males. After a median follow-up of 84 months, 32 patients are still on study. Hematologic (HR) and molecular responses (MR) were seen in 93 and 69% patients, respectively. Twenty-nine patients (50%) had a BM response, including 13 (22%) with a complete BM response (BM-CR). Moreover, 13 patients (22%) have experienced complete resolution of bone marrow reticulin fibrosis. Patients with BM response had higher duration of HR and MR, and lower discontinuation rate. Furthermore, patients with BM-CR had a higher probability of complete MR. The median duration of BM-CR was 30 months, and 9 patients have maintained their BM-CR (69%), including five who have maintained their response after discontinuation of therapy. Despite this observation, the pattern of HR, MR and BM response, their durability and interrelation was heterogeneous. Conclusions: Our results show the ability of PEG-IFN-α-2a to induce complete BM responses in a subset of ET and PV patients, but its correlation with durable clinically relevant treatment benefit warrants further investigation. Trial registration This study is registered with ClinicalTrials.gov (NCT00452023), and is ongoing but not enrolling new patients.

Original languageEnglish (US)
Article number30
JournalExperimental Hematology and Oncology
Volume6
Issue number1
DOIs
StatePublished - Nov 9 2017
Externally publishedYes

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Essential Thrombocythemia
Polycythemia Vera
Interferons
Bone Marrow
Therapeutics
Primary Myelofibrosis
Reticulin

Keywords

  • Essential thrombocythemia
  • Histomorphological response
  • Pegylated interferon alfa-2a
  • Polycythemia vera

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Histomorphological responses after therapy with pegylated interferon α-2a in patients with essential thrombocythemia (ET) and polycythemia vera (PV). / Masarova, Lucia; Yin, C. Cameron; Cortes, Jorge E.; Konopleva, Marina; Borthakur, Gautam; Newberry, Kate J.; Kantarjian, Hagop M.; Bueso-Ramos, Carlos E.; Verstovsek, Srdan.

In: Experimental Hematology and Oncology, Vol. 6, No. 1, 30, 09.11.2017.

Research output: Contribution to journalArticle

Masarova, Lucia ; Yin, C. Cameron ; Cortes, Jorge E. ; Konopleva, Marina ; Borthakur, Gautam ; Newberry, Kate J. ; Kantarjian, Hagop M. ; Bueso-Ramos, Carlos E. ; Verstovsek, Srdan. / Histomorphological responses after therapy with pegylated interferon α-2a in patients with essential thrombocythemia (ET) and polycythemia vera (PV). In: Experimental Hematology and Oncology. 2017 ; Vol. 6, No. 1.
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abstract = "Background: Pegylated interferon alfa-2a (PEG-IFN-α-2a) is a potent immunomodulating agent capable of inducing high rate of hematologic and even complete molecular remission in patients with essential thrombocythemia (ET) and polycythemia vera (PV). We recently reported results of a phase 2 trial of PEG-IFN-α-2a in 83 patients with ET and PV after a median follow-up of 83 months. Here we report an analysis of bone marrow (BM) responses in these patients. Methods: Among 83 patients, 58 (70{\%}, PV 25, ET 31) had evaluable BM samples. BM responses and fibrosis grading were defined according to the International Working Group for Myeloproliferative Neoplasms Research and Treatment, and the European Consensus on grading of BM fibrosis, respectively. BM was assessed prior to enrollment, and every 6-24 months while on therapy in all patients, and after therapy discontinuation in some patients. Results: The median age of analyzed 58 patients was 52 years, and 29{\%} were males. After a median follow-up of 84 months, 32 patients are still on study. Hematologic (HR) and molecular responses (MR) were seen in 93 and 69{\%} patients, respectively. Twenty-nine patients (50{\%}) had a BM response, including 13 (22{\%}) with a complete BM response (BM-CR). Moreover, 13 patients (22{\%}) have experienced complete resolution of bone marrow reticulin fibrosis. Patients with BM response had higher duration of HR and MR, and lower discontinuation rate. Furthermore, patients with BM-CR had a higher probability of complete MR. The median duration of BM-CR was 30 months, and 9 patients have maintained their BM-CR (69{\%}), including five who have maintained their response after discontinuation of therapy. Despite this observation, the pattern of HR, MR and BM response, their durability and interrelation was heterogeneous. Conclusions: Our results show the ability of PEG-IFN-α-2a to induce complete BM responses in a subset of ET and PV patients, but its correlation with durable clinically relevant treatment benefit warrants further investigation. Trial registration This study is registered with ClinicalTrials.gov (NCT00452023), and is ongoing but not enrolling new patients.",
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AU - Masarova, Lucia

AU - Yin, C. Cameron

AU - Cortes, Jorge E.

AU - Konopleva, Marina

AU - Borthakur, Gautam

AU - Newberry, Kate J.

AU - Kantarjian, Hagop M.

AU - Bueso-Ramos, Carlos E.

AU - Verstovsek, Srdan

PY - 2017/11/9

Y1 - 2017/11/9

N2 - Background: Pegylated interferon alfa-2a (PEG-IFN-α-2a) is a potent immunomodulating agent capable of inducing high rate of hematologic and even complete molecular remission in patients with essential thrombocythemia (ET) and polycythemia vera (PV). We recently reported results of a phase 2 trial of PEG-IFN-α-2a in 83 patients with ET and PV after a median follow-up of 83 months. Here we report an analysis of bone marrow (BM) responses in these patients. Methods: Among 83 patients, 58 (70%, PV 25, ET 31) had evaluable BM samples. BM responses and fibrosis grading were defined according to the International Working Group for Myeloproliferative Neoplasms Research and Treatment, and the European Consensus on grading of BM fibrosis, respectively. BM was assessed prior to enrollment, and every 6-24 months while on therapy in all patients, and after therapy discontinuation in some patients. Results: The median age of analyzed 58 patients was 52 years, and 29% were males. After a median follow-up of 84 months, 32 patients are still on study. Hematologic (HR) and molecular responses (MR) were seen in 93 and 69% patients, respectively. Twenty-nine patients (50%) had a BM response, including 13 (22%) with a complete BM response (BM-CR). Moreover, 13 patients (22%) have experienced complete resolution of bone marrow reticulin fibrosis. Patients with BM response had higher duration of HR and MR, and lower discontinuation rate. Furthermore, patients with BM-CR had a higher probability of complete MR. The median duration of BM-CR was 30 months, and 9 patients have maintained their BM-CR (69%), including five who have maintained their response after discontinuation of therapy. Despite this observation, the pattern of HR, MR and BM response, their durability and interrelation was heterogeneous. Conclusions: Our results show the ability of PEG-IFN-α-2a to induce complete BM responses in a subset of ET and PV patients, but its correlation with durable clinically relevant treatment benefit warrants further investigation. Trial registration This study is registered with ClinicalTrials.gov (NCT00452023), and is ongoing but not enrolling new patients.

AB - Background: Pegylated interferon alfa-2a (PEG-IFN-α-2a) is a potent immunomodulating agent capable of inducing high rate of hematologic and even complete molecular remission in patients with essential thrombocythemia (ET) and polycythemia vera (PV). We recently reported results of a phase 2 trial of PEG-IFN-α-2a in 83 patients with ET and PV after a median follow-up of 83 months. Here we report an analysis of bone marrow (BM) responses in these patients. Methods: Among 83 patients, 58 (70%, PV 25, ET 31) had evaluable BM samples. BM responses and fibrosis grading were defined according to the International Working Group for Myeloproliferative Neoplasms Research and Treatment, and the European Consensus on grading of BM fibrosis, respectively. BM was assessed prior to enrollment, and every 6-24 months while on therapy in all patients, and after therapy discontinuation in some patients. Results: The median age of analyzed 58 patients was 52 years, and 29% were males. After a median follow-up of 84 months, 32 patients are still on study. Hematologic (HR) and molecular responses (MR) were seen in 93 and 69% patients, respectively. Twenty-nine patients (50%) had a BM response, including 13 (22%) with a complete BM response (BM-CR). Moreover, 13 patients (22%) have experienced complete resolution of bone marrow reticulin fibrosis. Patients with BM response had higher duration of HR and MR, and lower discontinuation rate. Furthermore, patients with BM-CR had a higher probability of complete MR. The median duration of BM-CR was 30 months, and 9 patients have maintained their BM-CR (69%), including five who have maintained their response after discontinuation of therapy. Despite this observation, the pattern of HR, MR and BM response, their durability and interrelation was heterogeneous. Conclusions: Our results show the ability of PEG-IFN-α-2a to induce complete BM responses in a subset of ET and PV patients, but its correlation with durable clinically relevant treatment benefit warrants further investigation. Trial registration This study is registered with ClinicalTrials.gov (NCT00452023), and is ongoing but not enrolling new patients.

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