SAFETY AND EFFICACY OF RUXOLITINIB (RUX) IN PATIENTS WITH MYELOFIBROSIS (MF) AND ANEMIA (HB <10 G/DL): RESULTS AT WEEK (WK) 24 OF THE REALISE TRIAL
Author(s): ,
Francisco Cervantes
Affiliations:
Hospital Clínic, IDIBAPS, University of Barcelona,Barcelona,Spain
,
Heinz Gisslinger
Affiliations:
Department of Internal Medicine I,Division of Hematology and Hemostaseology, Comprehensive Cancer Center, Medical University of Vienna,Vienna,Austria
,
Atanas Radinoff
Affiliations:
University Hospital Sveti Ivan Rislki,Sofia,Bulgaria
,
Francesco Passamonti
Affiliations:
Department of Oncology-Hematology,University of Milan and BMT Unit, ASST Papa Giovanni XXIII,Bergamo,Italy
,
Lynda Foltz
Affiliations:
St Paul's Hospital, University of British Columbia,Vancouver,Canada
,
David M. Ross
Affiliations:
Royal Adelaide Hospital, and Flinders Medical Centre,Adelaide,Australia
,
Nicola Vianelli
Affiliations:
Institute of Hematology 'L. and A. Seràgnoli', Sant'Orsola-Malpighi University Hospital,Bologna,Italy
,
Francesco Mannelli
Affiliations:
CRIMM, Centro di Ricerca e Innovazione per le Malattie Mieloproliferative, Azienda Ospedaliera Universitaria Careggi, Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi,Firenze,Italy
,
Pierre Zachee
Affiliations:
Hematology Service,ZNA Stuivenberg,Antwerp,Belgium
,
Alexandr Myasnikov
Affiliations:
Department of Hematology,V.A. Baranov Republican Hospital,Petrozavodsk,Russian Federation
,
Evren Zor
Affiliations:
Novartis Pharma AG,Basel,Switzerland
,
Geralyn Gilotti
Affiliations:
Novartis Pharma,New Jersey,United States
,
Ranjan Tiwari
Affiliations:
Novartis Healthcare Pvt. Ltd.,Hyderabad,India
Haifa Kathrin Al-Ali
Affiliations:
University Hospital of Halle,Halle (Saale),Germany
EHA Library. Cervantes F. Jun 15, 2019; 267082; PS1465
Francisco Cervantes
Francisco Cervantes
Contributions
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Abstract

Abstract: PS1465

Type: Poster Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00

Location: Poster area

Background
RUX is the only approved JAK inhibitor for the treatment of disease-related splenomegaly or symptoms in adults with MF. Dose-dependent anemia has been observed with RUX, generally in the first 12 wks of treatment and is managed with dose adjustments and/or blood transfusions. Current label starting doses in MF are 5, 15, or 20 mg BID depending on platelet count (≥50 to <100×109/L, 100 to 200×109/L, >200×109/L, respectively), regardless of baseline Hb level.

Aims
To evaluate safety and efficacy of an alternative RUX dosing regimen in pts with MF and anemia (Hb <10g/dL): a starting dose of 10 mg BID for 12 wks and gradual up-titration.

Methods
A multicenter, phase II, open label, single arm study (NCT02966353). Eligible patients (pts) had primary MF, post-essential thrombocythemia (ET) MF or post-polycythemia vera (PV) MF, palpable (≥5 cm) spleen, Hb level <10 g/dL and platelet count ≥50x109/L. Pts started RUX at 10 mg BID and, after 12 wks, up titrations to 15 or 20 mg BID were allowed based on efficacy and platelet counts. The primary endpoint was proportion of pts achieving ≥50% reduction in spleen length (SL) at Wk 24. Secondary endpoints included transfusion requirements and dependence over time, safety (AEs), and patient-reported outcomes.

Results
Fifty-one pts (58.8% male, median age 67 years [45–88 years]) completed 24 wks of follow-up on treatment or discontinued treatment before data cutoff (24 July 2018). In total, 35 (68.6%) pts had primary MF, 11 (21.6%) had post-ET MF, and 5 (9.8%) had post-PV MF. Overall, 37.3, 54.9, and 7.8% of pts had ECOG performance scores of 0, 1, and 2, respectively. Proportions of pts per DIPSS category were: Int-1 17.6%, Int-2 54.9%, High 19.6%, unknown 7.8%. Median duration of exposure to RUX was 38.0 wks. At Wk 24, 63.6% (28/44) of pts had ≥50% SL reduction and 11.4% (5/44) had reductions of 25 to 50%. Hb levels dropped in the first 8 wks of treatment (median -6.0 g/L [-37.0 to +31.6 g/L]), then stabilized; platelet levels remained constant. At data cutoff, 32 pts were still undergoing treatment and 19 had discontinued (pt/guardian decision 13.7%, physician decision 7.8%, trial completion 5.9%, AEs 3.9%, death 3.9%, progressive disease 2.0%). Of 8 transfusion-dependent (TD; receiving ≥6 units of transfusions 12 wks prior to baseline) pts at baseline, ≥50% SL reduction was seen in 75.0% (6/8) of pts at Wk 24. Of 25 non-transfusion-dependent (NTD) pts at baseline, ≥50% SL reduction was seen in 70.8% (17/24) of pts at Wk 24. Eleven pts NTD at baseline became TD. Median dose was 20 mg/day (9–33 mg/day). At Wk 12, 10 pts had dose increases to 15 mg BID as per protocol for patients who have not achieved a 50% reduction in SL. A total of 23 pts had ≥1 dose reduction or interruption most commonly due to AEs (n=13, of which 10 were hematological). Most common grade 3/4 hematological AEs were anemia (27.5%) and thrombocytopenia (13.7%). The non-hematological AE occurring in >10% of pts was fatigue (11.8%). At Wk 24, using the MF-7 Total Symptom Score, 51.1% (23/45) of pts had a ≥50% reduction in total score from baseline. Similarly, 55.6% (25/45) of pts had a ≥50% reduction in Modified MFSAF v2.0 Total Symptom score from baseline.

Conclusion
An alternative dosing regimen of RUX 10 mg BID, with gradual up-titration after Wk 12, is efficacious in pts with MF and anemia (Hb <10g/dL), with safety and efficacy results comparable to previous RUX trials. A splenic response was seen at Wk 24 in both TD and NTD pts. These results indicate that treatment-emergent anemia early after starting RUX does not preclude splenic and symptomatic responses.

Session topic: 16. Myeloproliferative neoplasms - Clinical

Keyword(s): Anemia, Dose escalation, Myelofibrosis, Ruxolitinib

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