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RUXOLITINIB IN MYELOFIBROSIS: A MULTICENTRE EXPERIENCE FROM THE EAST OF ENGLAND
Author(s):
James Russell
,
James Russell
Affiliations:
Department of Haematology,Cambridge University Hospitals NHS Foundation Trust,Cambridge,United Kingdom
David Sparksman
,
David Sparksman
Affiliations:
James Paget University Hospital,Great Yarmouth,United Kingdom
Andra Dicu
,
Andra Dicu
Affiliations:
Norfolk and Norwich University Hospital,Norwich,United Kingdom
Kyaw Maw
,
Kyaw Maw
Affiliations:
James Paget University Hospital,Great Yarmouth,United Kingdom
Cesar Gomez
,
Cesar Gomez
Affiliations:
James Paget University Hospital,Great Yarmouth,United Kingdom
Manzoor Mangi
,
Manzoor Mangi
Affiliations:
James Paget University Hospital,Great Yarmouth,United Kingdom
Ioana Whalley
,
Ioana Whalley
Affiliations:
Ipswich Hospital,Ipswich,United Kingdom
Angela Collins
,
Angela Collins
Affiliations:
Norfolk and Norwich University Hospital,Norwich,United Kingdom
Shalal Sadullah
Shalal Sadullah
Affiliations:
James Paget University Hospital,Great Yarmouth,United Kingdom
(Abstract release date: 05/18/17) EHA Library. Russell J. 05/18/17; 182771; PB2057
Dr. James Russell
Dr. James Russell
Contributions
PDF Abstract
Abstract

Abstract: PB2057

Type: Publication Only

Background
Ruxolitinib, an oral Janus Kinase (JAK)1/JAK2 inhibitor, was approved in the EU in August 2012 for treating disease-related splenomegaly and constitutional symptoms in adults with primary myelofibrosis (PMF), post-polycythaemia vera myelofibrosis (PPV-MF), and post-essential thrombocythaemia myelofibrosis (PET-MF).

Aims
We present a retrospective multicentre analysis of MF patients treated with ruxolitinib from August 2012 to December 2016 at 3 centres in the East of England to assess its efficacy, safety, and tolerability in a 'real-world' clinical setting.

Methods
Retrospective data collection using electronic medical records and cancer registry data identified 49 MF patients treated with ruxolitinib at the James Paget, Norfolk and Norwich, and Ipswich hospitals (28, 14 and 7, respectively) over a 52-month period. Five had less than 3 months’ follow-up and were excluded.

Results

The patient group was 61.4% male, with a median age of 71 years (41–91). There were 16 (36.4%) patients with PMF, 13 (29.5%) with PPV-MF, 9 (20.5%) with PET-MF, and 6 (13.6%) with post-myeloproliferative disorder (unclassified)-MF. The indication for treatment was painful splenomegaly in 20 (45.5%) patients, constitutional symptoms in 23 (52.3%), and portal hypertension in 1 (2.3%). Ruxolitinib was first-line therapy in 10 (22.7%) patients, second-line in 24 (54.5%), and third-line or greater in 10 (22.7%). Starting doses ranged from 5mg BD in 2 (4.6%), 10mg BD in 14 (31.8%), 15mg BD in 11 (25%) and 20mg BD in 17 (38.6%), with occasional dose reduction/interruption primarily due to thrombocytopaenia. Fifteen (34.1%) patients were IPSS 3+, 22 (50%) IPSS 2, 6 (13.6%) IPSS 1, and 1 (2.3%) IPSS 0. Mutation analysis was available for 32 (72.7%) patients, of which 29 (90.6%) were JAK2 V617F-mutated, 2 (6.3%) were JAK2 V617F/exon 12-unmutated, and 1 (3.1%) was CALR-mutated. The median duration of treatment was 16.4 months (3–45) and median time to progression was 15.5 months (7–32). Progression-free survival (PFS) was 65.9% and overall survival (OS) 68.2%. Seven patients died from AML, 5 from progressive MF, and 2 from pneumonia. Multivariate analysis showed that ‘advancing age’ and ‘excess peripheral blasts (≥1%)’ were predictive of poor outcomes (HR 1.08, 95% CI 1.01-1.16; p=0.024 and HR 4.38, 95% CI 1.12-17.09; p=0.033, respectively). Clinical assessment of spleen size was available for 29 (65.9%) patients and showed a reduction in splenomegaly in 16 (55.2%), an increase in 8 (27.6%) and no change in 5 (17.2%). Weight gain occurred in 32 (72.7%) and demonstrated a strong survival advantage (HR 0.21, 95% CI 0.07-0.65; p=0.006). The most common haematologic adverse events (AEs) were cytopaenias. Forty patients (90.9%) had anaemia and 22 (50%) were transfusion-dependent, compared with 29 (65.9%) and 10 (22.7%) pre-treatment, respectively. Thirteen (29.5%) patients also received an erythropoiesis-stimulating agent. Thirty-one (70.5%) patients had thrombocytopaenia (6.8% grade 4) compared with 13 (29.5%) pre-treatment. The most frequent non-haematologic AEs were minor infections, documented in 17 patients (38.6%), and included lower respiratory tract infections, candidiasis, and HSV/VZV reactivation. One patient died from Aspergillus pneumonia. Twenty-nine patients (65.9%) remain on treatment.

Conclusion
Ruxolitinib was well-tolerated and effective in improving constitutional symptoms in our 'real-world' study population. Therapeutic response and safety profile was similar to trial data although we observed a higher incidence of minor haematologic AEs that were readily managed with supportive care. Weight gain was associated with a strong survival advantage and could prove a useful clinical marker of response. The majority of patients remain on active treatment.

Session topic: 16. Myeloproliferative neoplasms - Clinical

Keyword(s): Ruxolitinib, Myelofibrosis, Janus Kinase inhibitor, Clinical data

Abstract: PB2057

Type: Publication Only

Background
Ruxolitinib, an oral Janus Kinase (JAK)1/JAK2 inhibitor, was approved in the EU in August 2012 for treating disease-related splenomegaly and constitutional symptoms in adults with primary myelofibrosis (PMF), post-polycythaemia vera myelofibrosis (PPV-MF), and post-essential thrombocythaemia myelofibrosis (PET-MF).

Aims
We present a retrospective multicentre analysis of MF patients treated with ruxolitinib from August 2012 to December 2016 at 3 centres in the East of England to assess its efficacy, safety, and tolerability in a 'real-world' clinical setting.

Methods
Retrospective data collection using electronic medical records and cancer registry data identified 49 MF patients treated with ruxolitinib at the James Paget, Norfolk and Norwich, and Ipswich hospitals (28, 14 and 7, respectively) over a 52-month period. Five had less than 3 months’ follow-up and were excluded.

Results

The patient group was 61.4% male, with a median age of 71 years (41–91). There were 16 (36.4%) patients with PMF, 13 (29.5%) with PPV-MF, 9 (20.5%) with PET-MF, and 6 (13.6%) with post-myeloproliferative disorder (unclassified)-MF. The indication for treatment was painful splenomegaly in 20 (45.5%) patients, constitutional symptoms in 23 (52.3%), and portal hypertension in 1 (2.3%). Ruxolitinib was first-line therapy in 10 (22.7%) patients, second-line in 24 (54.5%), and third-line or greater in 10 (22.7%). Starting doses ranged from 5mg BD in 2 (4.6%), 10mg BD in 14 (31.8%), 15mg BD in 11 (25%) and 20mg BD in 17 (38.6%), with occasional dose reduction/interruption primarily due to thrombocytopaenia. Fifteen (34.1%) patients were IPSS 3+, 22 (50%) IPSS 2, 6 (13.6%) IPSS 1, and 1 (2.3%) IPSS 0. Mutation analysis was available for 32 (72.7%) patients, of which 29 (90.6%) were JAK2 V617F-mutated, 2 (6.3%) were JAK2 V617F/exon 12-unmutated, and 1 (3.1%) was CALR-mutated. The median duration of treatment was 16.4 months (3–45) and median time to progression was 15.5 months (7–32). Progression-free survival (PFS) was 65.9% and overall survival (OS) 68.2%. Seven patients died from AML, 5 from progressive MF, and 2 from pneumonia. Multivariate analysis showed that ‘advancing age’ and ‘excess peripheral blasts (≥1%)’ were predictive of poor outcomes (HR 1.08, 95% CI 1.01-1.16; p=0.024 and HR 4.38, 95% CI 1.12-17.09; p=0.033, respectively). Clinical assessment of spleen size was available for 29 (65.9%) patients and showed a reduction in splenomegaly in 16 (55.2%), an increase in 8 (27.6%) and no change in 5 (17.2%). Weight gain occurred in 32 (72.7%) and demonstrated a strong survival advantage (HR 0.21, 95% CI 0.07-0.65; p=0.006). The most common haematologic adverse events (AEs) were cytopaenias. Forty patients (90.9%) had anaemia and 22 (50%) were transfusion-dependent, compared with 29 (65.9%) and 10 (22.7%) pre-treatment, respectively. Thirteen (29.5%) patients also received an erythropoiesis-stimulating agent. Thirty-one (70.5%) patients had thrombocytopaenia (6.8% grade 4) compared with 13 (29.5%) pre-treatment. The most frequent non-haematologic AEs were minor infections, documented in 17 patients (38.6%), and included lower respiratory tract infections, candidiasis, and HSV/VZV reactivation. One patient died from Aspergillus pneumonia. Twenty-nine patients (65.9%) remain on treatment.

Conclusion
Ruxolitinib was well-tolerated and effective in improving constitutional symptoms in our 'real-world' study population. Therapeutic response and safety profile was similar to trial data although we observed a higher incidence of minor haematologic AEs that were readily managed with supportive care. Weight gain was associated with a strong survival advantage and could prove a useful clinical marker of response. The majority of patients remain on active treatment.

Session topic: 16. Myeloproliferative neoplasms - Clinical

Keyword(s): Ruxolitinib, Myelofibrosis, Janus Kinase inhibitor, Clinical data

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