Benefit of Early Ruxolitinib Initiation Regardless of Fibrosis Grade in Patients with Primary Myelofibrosis: A Post Hoc Analysis of the Single-Arm Phase 3b JUMP Study
by
, , ,
Francesca Palandri
1,*
,
Haifa Kathrin Al-Ali
2
,
Paola Guglielmelli
3
,
Mike W. Zuurman
4,†,
Rajendra Sarkar
5 and
Vikas Gupta
6 1
Istituto di Ematologia “Seràgnoli”, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
2
University Hospital Halle, 06120 Halle (Saale), Germany
3
Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera-Universitaria Careggi, University of Florence, 50134 Florence, Italy
4
Novartis Pharma AG, 4056 Basel, Switzerland
5
Novartis Healthcare Private Limited, Hyderabad 500081, India
6
Princess Margaret Cancer Centre, Toronto, ON M5G 2C4, Canada
*
Author to whom correspondence should be addressed.
†
Current address: Menarini Group, 50131 Florence, Italy.
Cancers 2023, 15(10), 2859; https://doi.org/10.3390/cancers15102859
Submission received: 28 February 2023
/
Revised: 28 April 2023
/
Accepted: 11 May 2023
/
Published: 22 May 2023
(This article belongs to the Section Cancer Therapy)
Simple Summary
Bone marrow fibrosis (BMF) is a hallmark of myelofibrosis (a rare blood cancer), and BMF severity may be useful in predicting patient response to treatment, since high-severity BMF is associated with poor survival. In this study, we studied how BMF severity and early (within 2 years of diagnosis) versus late (more than 2 years after diagnosis) initiation of ruxolitinib treatment affected the response to treatment in patients with primary myelofibrosis. Our results showed that patients with low-severity BMF had a better response to treatment with ruxolitinib and longer survival; however, all patients treated with ruxolitinib showed improvements in spleen size and survival, regardless of their BMF severity. Our data also showed that initiation of early treatment with ruxolitinib resulted in better responses in all patients. This study showed that treatment with ruxolitinib can benefit patients with both low- and high-severity BMF, especially when it is started early.
Abstract
Bone marrow fibrosis (BMF) is an adverse prognostic factor for myelofibrosis (MF). The single-arm, open-label, phase 3b JUMP trial (NCT01493414) assessed the safety and efficacy of the JAK1/JAK2 inhibitor ruxolitinib in patients with symptomatic MF. This post hoc analysis investigated the impact of BMF grade on response and outcomes in patients with primary MF (PMF) from the JUMP study. BMF was assessed by biopsy and graded from 0 to 3; grades 0–1 were considered low-grade fibrosis (LGF) and grades 2–3 were considered high-grade fibrosis (HGF). Patients with LGF (n = 268) had lower rates of cytopenias at baseline but showed comparable disease burden vs. patients with HGF (n = 852). The proportion of patients achieving a spleen response was greater in the LGF group vs. the HGF group at Week 24 and at any time during the study, while overall survival estimates were improved in patients with LGF vs. patients with HGF. Early initiation of ruxolitinib therapy (within 2 years of diagnosis) was associated with increased response rates in all patients. These results highlight the efficacy of ruxolitinib in symptomatic patients with PMF, with the greatest clinical improvements observed in patients with LGF and in patients who received early treatment.
