Interim analysis of safety and efficacy of ruxolitinib in patients with myelofibrosis and low platelet counts

Moshe Talpaz, Ronald Paquette, Lawrence Afrin, Solomon I. Hamburg, Josef T. Prchal, Katarzyna Jamieson, Howard R. Terebelo, Gregory L. Ortega, Roger M. Lyons, Ramon V. Tiu, Elliott F. Winton, Kavita Natrajan, Olatoyosi Odenike, David Claxton, Wei Peng, Peter O'Neill, Susan Erickson-Viitanen, Lance Leopold, Victor Sandor, Richard S. Levy & 2 others Hagop M. Kantarjian, Srdan Verstovsek

Research output: Contribution to journalArticle

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Abstract

Background: Ruxolitinib, a Janus kinase 1 and 2 inhibitor, demonstrated improvements in spleen volume, symptoms, and survival over placebo and best available therapy in intermediate-2 or high-risk myelofibrosis patients with baseline platelet counts ≥100 × 109/L in phase III studies. The most common adverse events were dose-dependent anemia and thrombocytopenia, which were anticipated because thrombopoietin and erythropoietin signal through JAK2. These events were manageable, rarely leading to treatment discontinuation. Because approximately one-quarter of MF patients have platelet counts <100 × 109/L consequent to their disease, ruxolitinib was evaluated in this subset of patients using lower initial doses. Interim results of a phase II study of ruxolitinib in myelofibrosis patients with baseline platelet counts of 50-100 × 109/L are reported. Methods. Ruxolitinib was initiated at a dose of 5 mg twice daily (BID), and doses could be increased by 5 mg once daily every 4 weeks to 10 mg BID if platelet counts remained adequate. Additional dosage increases required evidence of suboptimal efficacy. Assessments included measurement of spleen volume by MRI, MF symptoms by MF Symptom Assessment Form v2.0 Total Symptom Score [TSS]), Patient Global Impression of Change (PGIC); EORTC QLQ-C30, and safety/tolerability. Results: By week 24, 62% of patients achieved stable doses ≥10 mg BID. Median reductions in spleen volume and TSS were 24.2% and 43.8%, respectively. Thrombocytopenia necessitating dose reductions and dose interruptions occurred in 12 and 8 patients, respectively, and occurred mainly in patients with baseline platelet counts ≤75 × 109/L. Seven patients experienced platelet count increases ≥15 × 109/L. Mean hemoglobin levels remained stable over the treatment period. Two patients discontinued for adverse events: 1 for grade 4 retroperitoneal hemorrhage secondary to multiple and suspected pre-existing renal artery aneurysms and 1 for grade 4 thrombocytopenia. Conclusions: Results suggest that a low starting dose of ruxolitinib with escalation to 10 mg BID may be appropriate in myelofibrosis patients with low platelet counts. Trial registration. ClinicalTrials.gov: NCT01348490.

Original languageEnglish (US)
Article number81
JournalJournal of Hematology and Oncology
Volume6
Issue number1
DOIs
StatePublished - Oct 31 2013

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Primary Myelofibrosis
Platelet Count
Safety
Spleen
Thrombocytopenia
Janus Kinase 1
INCB018424
Janus Kinase 2
Thrombopoietin
Symptom Assessment
Renal Artery
Erythropoietin
Aneurysm
Anemia
Hemoglobins
Therapeutics
Placebos
Hemorrhage

Keywords

  • Janus kinase inhibitor
  • Myelofibrosis
  • Phase II
  • Platelet count
  • Ruxolitinib
  • Spleen volume
  • Total symptom score

ASJC Scopus subject areas

  • Hematology
  • Molecular Biology
  • Oncology
  • Cancer Research

Cite this

Talpaz, M., Paquette, R., Afrin, L., Hamburg, S. I., Prchal, J. T., Jamieson, K., ... Verstovsek, S. (2013). Interim analysis of safety and efficacy of ruxolitinib in patients with myelofibrosis and low platelet counts. Journal of Hematology and Oncology, 6(1), [81]. https://doi.org/10.1186/1756-8722-6-81

Interim analysis of safety and efficacy of ruxolitinib in patients with myelofibrosis and low platelet counts. / Talpaz, Moshe; Paquette, Ronald; Afrin, Lawrence; Hamburg, Solomon I.; Prchal, Josef T.; Jamieson, Katarzyna; Terebelo, Howard R.; Ortega, Gregory L.; Lyons, Roger M.; Tiu, Ramon V.; Winton, Elliott F.; Natrajan, Kavita; Odenike, Olatoyosi; Claxton, David; Peng, Wei; O'Neill, Peter; Erickson-Viitanen, Susan; Leopold, Lance; Sandor, Victor; Levy, Richard S.; Kantarjian, Hagop M.; Verstovsek, Srdan.

In: Journal of Hematology and Oncology, Vol. 6, No. 1, 81, 31.10.2013.

Research output: Contribution to journalArticle

Talpaz, M, Paquette, R, Afrin, L, Hamburg, SI, Prchal, JT, Jamieson, K, Terebelo, HR, Ortega, GL, Lyons, RM, Tiu, RV, Winton, EF, Natrajan, K, Odenike, O, Claxton, D, Peng, W, O'Neill, P, Erickson-Viitanen, S, Leopold, L, Sandor, V, Levy, RS, Kantarjian, HM & Verstovsek, S 2013, 'Interim analysis of safety and efficacy of ruxolitinib in patients with myelofibrosis and low platelet counts', Journal of Hematology and Oncology, vol. 6, no. 1, 81. https://doi.org/10.1186/1756-8722-6-81
Talpaz, Moshe ; Paquette, Ronald ; Afrin, Lawrence ; Hamburg, Solomon I. ; Prchal, Josef T. ; Jamieson, Katarzyna ; Terebelo, Howard R. ; Ortega, Gregory L. ; Lyons, Roger M. ; Tiu, Ramon V. ; Winton, Elliott F. ; Natrajan, Kavita ; Odenike, Olatoyosi ; Claxton, David ; Peng, Wei ; O'Neill, Peter ; Erickson-Viitanen, Susan ; Leopold, Lance ; Sandor, Victor ; Levy, Richard S. ; Kantarjian, Hagop M. ; Verstovsek, Srdan. / Interim analysis of safety and efficacy of ruxolitinib in patients with myelofibrosis and low platelet counts. In: Journal of Hematology and Oncology. 2013 ; Vol. 6, No. 1.
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T1 - Interim analysis of safety and efficacy of ruxolitinib in patients with myelofibrosis and low platelet counts

AU - Talpaz, Moshe

AU - Paquette, Ronald

AU - Afrin, Lawrence

AU - Hamburg, Solomon I.

AU - Prchal, Josef T.

AU - Jamieson, Katarzyna

AU - Terebelo, Howard R.

AU - Ortega, Gregory L.

AU - Lyons, Roger M.

AU - Tiu, Ramon V.

AU - Winton, Elliott F.

AU - Natrajan, Kavita

AU - Odenike, Olatoyosi

AU - Claxton, David

AU - Peng, Wei

AU - O'Neill, Peter

AU - Erickson-Viitanen, Susan

AU - Leopold, Lance

AU - Sandor, Victor

AU - Levy, Richard S.

AU - Kantarjian, Hagop M.

AU - Verstovsek, Srdan

PY - 2013/10/31

Y1 - 2013/10/31

N2 - Background: Ruxolitinib, a Janus kinase 1 and 2 inhibitor, demonstrated improvements in spleen volume, symptoms, and survival over placebo and best available therapy in intermediate-2 or high-risk myelofibrosis patients with baseline platelet counts ≥100 × 109/L in phase III studies. The most common adverse events were dose-dependent anemia and thrombocytopenia, which were anticipated because thrombopoietin and erythropoietin signal through JAK2. These events were manageable, rarely leading to treatment discontinuation. Because approximately one-quarter of MF patients have platelet counts <100 × 109/L consequent to their disease, ruxolitinib was evaluated in this subset of patients using lower initial doses. Interim results of a phase II study of ruxolitinib in myelofibrosis patients with baseline platelet counts of 50-100 × 109/L are reported. Methods. Ruxolitinib was initiated at a dose of 5 mg twice daily (BID), and doses could be increased by 5 mg once daily every 4 weeks to 10 mg BID if platelet counts remained adequate. Additional dosage increases required evidence of suboptimal efficacy. Assessments included measurement of spleen volume by MRI, MF symptoms by MF Symptom Assessment Form v2.0 Total Symptom Score [TSS]), Patient Global Impression of Change (PGIC); EORTC QLQ-C30, and safety/tolerability. Results: By week 24, 62% of patients achieved stable doses ≥10 mg BID. Median reductions in spleen volume and TSS were 24.2% and 43.8%, respectively. Thrombocytopenia necessitating dose reductions and dose interruptions occurred in 12 and 8 patients, respectively, and occurred mainly in patients with baseline platelet counts ≤75 × 109/L. Seven patients experienced platelet count increases ≥15 × 109/L. Mean hemoglobin levels remained stable over the treatment period. Two patients discontinued for adverse events: 1 for grade 4 retroperitoneal hemorrhage secondary to multiple and suspected pre-existing renal artery aneurysms and 1 for grade 4 thrombocytopenia. Conclusions: Results suggest that a low starting dose of ruxolitinib with escalation to 10 mg BID may be appropriate in myelofibrosis patients with low platelet counts. Trial registration. ClinicalTrials.gov: NCT01348490.

AB - Background: Ruxolitinib, a Janus kinase 1 and 2 inhibitor, demonstrated improvements in spleen volume, symptoms, and survival over placebo and best available therapy in intermediate-2 or high-risk myelofibrosis patients with baseline platelet counts ≥100 × 109/L in phase III studies. The most common adverse events were dose-dependent anemia and thrombocytopenia, which were anticipated because thrombopoietin and erythropoietin signal through JAK2. These events were manageable, rarely leading to treatment discontinuation. Because approximately one-quarter of MF patients have platelet counts <100 × 109/L consequent to their disease, ruxolitinib was evaluated in this subset of patients using lower initial doses. Interim results of a phase II study of ruxolitinib in myelofibrosis patients with baseline platelet counts of 50-100 × 109/L are reported. Methods. Ruxolitinib was initiated at a dose of 5 mg twice daily (BID), and doses could be increased by 5 mg once daily every 4 weeks to 10 mg BID if platelet counts remained adequate. Additional dosage increases required evidence of suboptimal efficacy. Assessments included measurement of spleen volume by MRI, MF symptoms by MF Symptom Assessment Form v2.0 Total Symptom Score [TSS]), Patient Global Impression of Change (PGIC); EORTC QLQ-C30, and safety/tolerability. Results: By week 24, 62% of patients achieved stable doses ≥10 mg BID. Median reductions in spleen volume and TSS were 24.2% and 43.8%, respectively. Thrombocytopenia necessitating dose reductions and dose interruptions occurred in 12 and 8 patients, respectively, and occurred mainly in patients with baseline platelet counts ≤75 × 109/L. Seven patients experienced platelet count increases ≥15 × 109/L. Mean hemoglobin levels remained stable over the treatment period. Two patients discontinued for adverse events: 1 for grade 4 retroperitoneal hemorrhage secondary to multiple and suspected pre-existing renal artery aneurysms and 1 for grade 4 thrombocytopenia. Conclusions: Results suggest that a low starting dose of ruxolitinib with escalation to 10 mg BID may be appropriate in myelofibrosis patients with low platelet counts. Trial registration. ClinicalTrials.gov: NCT01348490.

KW - Janus kinase inhibitor

KW - Myelofibrosis

KW - Phase II

KW - Platelet count

KW - Ruxolitinib

KW - Spleen volume

KW - Total symptom score

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