Scholarlink

Background <p>Myelodysplastic syndrome and myeloproliferative neoplasm (MDS/MPN) overlap syndromes are characterized by the presence of features of both MDS and MPN and have a poor prognosis. We conducted a phase 2 clinical trial evaluating the combination of Azacitidine (AZA) and Ruxolitinib (RUX) in MDS/MPN, with interim analysis showing an objective response rate of 57%. Herein, we report the final analysis from this clinical trial, including long-term survival data.</p> Methods <p>This was an open-label phase 2 clinical trial including adult patients in 2 diagnostic arms: myelofibrosis (arm 1) and MDS/MPN (arm 2). This manuscript reports outcomes of MDS/MPN patients. RUX 5–20&#xa0;mg twice daily (per RUX label) was administered in 28-day cycles, and AZA 25 mg/m<sup>2</sup> on days 1–5 was added starting cycle 4. Primary endpoint was objective response rate per the 2015 International Consortium Proposal (ICP) MDS/MPN response criteria.</p> Results <p>From 5/2013 to 8/2022, 52 patients were treated with a median age of 68 years (range, 39–82). Disease subtypes were MDS/MPN-Unclassifiable in 24 patients (46%), chronic myelomonocytic leukemia in 23 patients (44%), and atypical chronic myeloid leukemia in 5 patients (10%). Majority of patients (<i>n</i> = 40, 77%) had intermediate-2/high-risk disease by Dynamic International Prognosis Scoring System criteria. Objective responses were attained in 30 patients (58%), with a median duration of response of 13.6 months (95% CI: 6.4–41.1). After a median follow up of 88.5 months, 13 (25%) patients are alive, with median overall survival (OS) of 26.7 months (95% CI: 16.5–52.7), 5-year OS 33%. Median OS in MDS/MPN-U and CMML was 52.7 months (5-year OS 46%) and 17.5 months (5-year OS 27%), respectively. Twelve patients (23%) underwent allogeneic stem cell transplantation; with median OS not reached, 5-year OS 51%. Transformation to acute myeloid leukemia occurred in 13 patients (25%). The most common grade 3–5 adverse events (AEs) regardless of attribution were anemia (31, 60%), thrombocytopenia (27, 52%) and pneumonia (17, 33%). AE-related treatment discontinuation occurred in only 3 patients (6%).</p> Conclusions <p>AZA-RUX therapy led to durable responses and encouraging OS in MDS/MPN with a manageable safety profile.</p> Trial registration <p>NCT01787487, (clinicaltrials.gov, date: 2/6/2013)</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Final analysis of phase 2 clinical trial of ruxolitinib and azacitidine combination therapy in patients with myelodysplastic syndrome/myeloproliferative neoplasms

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月16日

查看全文
  • Sankalp Arora,
  • Jayastu Senapati,
  • Indraneel Deshmukh,
  • Prithviraj Bose,
  • Lucia Masarova,
  • Sanam Loghavi,
  • Xuemei Wang,
  • Graciela Nogueras-Gonzalez,
  • Guillermo Montalban-Bravo,
  • Gautam Borthakur,
  • Courtney D. DiNardo,
  • Tapan Kadia,
  • Lingsha Zhou,
  • Dyana Saenz,
  • Habiba Halim,
  • Yesid Alvarado,
  • Maro Ohanian,
  • Koichi Takahashi,
  • Nicholas J. Short,
  • Elias Jabbour,
  • Farhad Ravandi,
  • Guillermo Garcia-Manero,
  • Naveen Pemmaraju,
  • Naval G. Daver

摘要

Background

Myelodysplastic syndrome and myeloproliferative neoplasm (MDS/MPN) overlap syndromes are characterized by the presence of features of both MDS and MPN and have a poor prognosis. We conducted a phase 2 clinical trial evaluating the combination of Azacitidine (AZA) and Ruxolitinib (RUX) in MDS/MPN, with interim analysis showing an objective response rate of 57%. Herein, we report the final analysis from this clinical trial, including long-term survival data.

Methods

This was an open-label phase 2 clinical trial including adult patients in 2 diagnostic arms: myelofibrosis (arm 1) and MDS/MPN (arm 2). This manuscript reports outcomes of MDS/MPN patients. RUX 5–20 mg twice daily (per RUX label) was administered in 28-day cycles, and AZA 25 mg/m2 on days 1–5 was added starting cycle 4. Primary endpoint was objective response rate per the 2015 International Consortium Proposal (ICP) MDS/MPN response criteria.

Results

From 5/2013 to 8/2022, 52 patients were treated with a median age of 68 years (range, 39–82). Disease subtypes were MDS/MPN-Unclassifiable in 24 patients (46%), chronic myelomonocytic leukemia in 23 patients (44%), and atypical chronic myeloid leukemia in 5 patients (10%). Majority of patients (n = 40, 77%) had intermediate-2/high-risk disease by Dynamic International Prognosis Scoring System criteria. Objective responses were attained in 30 patients (58%), with a median duration of response of 13.6 months (95% CI: 6.4–41.1). After a median follow up of 88.5 months, 13 (25%) patients are alive, with median overall survival (OS) of 26.7 months (95% CI: 16.5–52.7), 5-year OS 33%. Median OS in MDS/MPN-U and CMML was 52.7 months (5-year OS 46%) and 17.5 months (5-year OS 27%), respectively. Twelve patients (23%) underwent allogeneic stem cell transplantation; with median OS not reached, 5-year OS 51%. Transformation to acute myeloid leukemia occurred in 13 patients (25%). The most common grade 3–5 adverse events (AEs) regardless of attribution were anemia (31, 60%), thrombocytopenia (27, 52%) and pneumonia (17, 33%). AE-related treatment discontinuation occurred in only 3 patients (6%).

Conclusions

AZA-RUX therapy led to durable responses and encouraging OS in MDS/MPN with a manageable safety profile.

Trial registration

NCT01787487, (clinicaltrials.gov, date: 2/6/2013)