Addition of Navitoclax to Ongoing Ruxolitinib Therapy for Patients With Myelofibrosis With Progression or Suboptimal Response: Phase II Safety and Efficacy

被引：92

作者：

Harrison, Claire N. ^{[1
]}

Garcia, Jacqueline S. ^{[2
]}

Somervaille, Tim C. P. ^{[3
,4
]}

Foran, James M. ^{[5
]}

Verstovsek, Srdan ^{[6
]}

Jamieson, Catriona ^{[7
]}

Mesa, Ruben ^{[8
]}

Ritchie, Ellen K. ^{[9
]}

Tantravahi, Srinivas K. ^{[10
,11
]}

Vachhani, Pankit ^{[12
]}

O'Connell, Casey L. ^{[13
]}

Komrokji, Rami S. ^{[14
]}

Harb, Jason ^{[15
]}

Hutti, Jessica E. ^{[15
]}

Holes, Leanne ^{[15
]}

Masud, Abdullah A. ^{[15
]}

Nuthalapati, Silpa ^{[15
]}

Potluri, Jalaja ^{[15
]}

Pemmaraju, Naveen ^{[6
]}

机构：

[1] Guys & St Thomas NHS Fdn Trust, London, England

[2] Dana Farber Canc Inst, Boston, MA 02115 USA

[3] Christie NHS Fdn Trust, Manchester, Lancs, England

[4] Univ Manchester, Canc Res UK Manchester Inst, Manchester, Lancs, England

[5] Mayo Clin, Jacksonville, FL 32224 USA

[6] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA

[7] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA

[8] Univ Texas Hlth San Antonio, San Antonio, TX USA

[9] Weill Cornell Med Coll, Div Hematol & Oncol, New York, NY USA

[10] Univ Utah, Salt Lake City, UT USA

[11] Huntsman Canc Inst, Salt Lake City, UT USA

[12] ONeal Comprehens Canc Ctr UAB, Birmingham, AL USA

[13] Univ Southern Calif, Keck Sch Med, Los Angeles, CA 90007 USA

[14] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA

[15] AbbVie Inc, N Chicago, IL USA

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2022年 / 40卷 / 15期

关键词：

MYELOPROLIFERATIVE NEOPLASMS RESEARCH; INTERNATIONAL WORKING GROUP; SYMPTOM ASSESSMENT FORM; AVAILABLE THERAPY; IWG-MRT; OUTCOMES; INHIBITOR; JAK2; GUIDELINES; CONSENSUS;

D O I：

10.1200/JCO.21.02188

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

PURPOSE Targeting the BCL-XL pathway has demonstrated the ability to overcome Janus kinase inhibitor resistance in preclinical models. This phase II trial investigated the efficacy and safety of adding BCL-XL/BCL-2 inhibitor navitoclax to ruxolitinib therapy in patients with myelofibrosis with progression or suboptimal response to ruxolitinib monotherapy (ClinicalTrials.gov identifier: NCT03222609). METHODS Thirty-four adult patients with intermediate-/high-risk myelofibrosis who had progression or suboptimal response on stable ruxolitinib dose (>= 10 mg twice daily) were administered navitoclax at 50 mg once daily starting dose, followed by escalation to a maximum of 300 mg once daily in once in weekly increments (if platelets were >= 75x10(9)/L). The primary end point was >= 35% spleen volume reduction (SVR35) from baseline at week 24. Secondary end points included >= 50% reduction in total symptom score (TSS50) from baseline at week 24, hemoglobin improvement, change in bone marrow fibrosis (BMF) grade, and safety. RESULTS High molecular risk mutations were identified in 58% of patients, and 52% harbored >= 3 mutations. SVR35 was achieved by 26.5% of patients at week 24, and by 41%, at any time on study, with an estimated median duration of SVR35 of 13.8months. TSS50 was achieved by 30% (6 of 20) of patients at week 24, and BMF improved by 1-2 grades in 33% (11 of 33) of evaluable patients. Anemia response was achieved by 64% (7 of 11), including one patient with baseline transfusion dependence. Median overall survival was not reached with a median follow-up of 21.6 months. The most common adverse event was reversible thrombocytopenia without clinically significant bleeding (88%). CONCLUSION The addition of navitoclax to ruxolitinib in patients with persistent or progressive myelofibrosis resulted in durable SVR35, improved TSS, hemoglobin response, and BMF. Further investigation is underway to qualify the potential for disease modification. (C) 2022 by American Society of Clinical Oncology

引用

页码：1671 / +

页数：11

共 45 条

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