Gilteritinib as Post-Transplant Maintenance for AML With Internal Tandem Duplication Mutation of FLT3

被引：85

作者：

Levis, Mark J. ^{[1
]}

Hamadani, Mehdi ^{[2
]}

Logan, Brent ^{[2
]}

Jones, Richard J. ^{[1
]}

Singh, Anurag K. ^{[3
]}

Litzow, Mark ^{[4
]}

Wingard, John R. ^{[5
]}

Papadopoulos, Esperanza B. ^{[6
]}

Perl, Alexander E. ^{[7
]}

Soiffer, Robert J. ^{[8
]}

Ustun, Celalettin ^{[9
]}

Ueda Oshima, Masumi ^{[10
]}

Uy, Geoffrey L. ^{[11
]}

Waller, Edmund K. ^{[12
]}

Vasu, Sumithra ^{[13
]}

Solh, Melhem ^{[14
]}

Mishra, Asmita ^{[15
]}

Muffly, Lori ^{[16
]}

Kim, Hee-Je ^{[17
]}

Mikesch, Jan-Henrik ^{[18
]}

Najima, Yuho ^{[19
]}

Onozawa, Masahiro ^{[20
]}

Thomson, Kirsty ^{[21
]}

Nagler, Arnon ^{[22
]}

Wei, Andrew H. ^{[23
,24
]}

Marcucci, Guido ^{[25
]}

Geller, Nancy L. ^{[26
]}

Hasabou, Nahla ^{[27
]}

Delgado, David ^{[27
]}

Rosales, Matt ^{[27
]}

Hill, Jason ^{[27
]}

Gill, Stanley C. ^{[27
]}

Nuthethi, Rishita ^{[27
]}

King, Denise ^{[28
]}

Wittsack, Heather ^{[28
]}

Mendizabal, Adam ^{[28
]}

Devine, Steven M. ^{[29
]}

Horowitz, Mary M. ^{[2
]}

Chen, Yi-Bin ^{[30
]}

机构：

[1] Johns Hopkins Univ, Baltimore, MD USA

[2] Med Coll Wisconsin, CIBMTR, Milwaukee, WI USA

[3] Univ Kansas, Kansas City, KS USA

[4] Mayo Clin, Rochester, MN USA

[5] Univ Florida, Gainesville, FL USA

[6] Mem Sloan Kettering Canc Ctr, New York, NY USA

[7] Univ Penn, Philadelphia, PA USA

[8] Dana Farber Canc Inst, Boston, MA USA

[9] Rush Univ, Med Ctr, Chicago, IL USA

[10] Fred Hutchinson Canc Ctr, Seattle, WA USA

[11] Washington Univ, St Louis, MO USA

[12] Emory Univ, Atlanta, GA USA

[13] Ohio State Univ, Columbus, OH USA

[14] Northside Hosp, Canc Inst, Atlanta, GA USA

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

[16] Stanford Univ, Palo Alto, CA USA

[17] Catholic Univ Korea, Catholic Hematol Hosp, Seoul St Marys Hosp, Coll Med, Seoul, South Korea

[18] Univ Munster, Munster, Germany

[19] Komagome Hosp, Tokyo Metropolitan Canc & Infect Dis Ctr, Tokyo, Japan

[20] Hokkaido Univ Hosp, Sapporo, Japan

[21] Univ Coll Hosp, London, England

[22] Chaim Sheba Med Ctr, Tel Hashomer, Israel

[23] Royal Melbourne Hosp, Walterand Eliza Hill Inst Med Res, Peter MacCallum Canc Ctr, Melbourne, Australia

[24] Univ Melbourne, Melbourne, Australia

[25] Beckman Res Inst City Hope, Duarte, CA USA

[26] NHLBI, Bethesda, MD USA

[27] Astellas Pharma Inc, Northbrook, IL USA

[28] Emmes Co, Rockville, MD USA

[29] Natl Marrow Donor Program, Minneapolis, MN USA

[30] Massachusetts Gen Hosp, Boston, MA USA

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2024年 / 42卷 / 15期

关键词：

ACUTE MYELOID-LEUKEMIA; MINIMAL RESIDUAL DISEASE; STEM-CELL TRANSPLANTATION; EUROPEAN LEUKEMIANET; IMPACT; CHEMOTHERAPY;

D O I：

10.1200/JCO.23.02474

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

PURPOSE Allogeneic hematopoietic cell transplantation (HCT) improves outcomes for patients with AML harboring an internal tandem duplication mutation of FLT3 (FLT3-ITD) AML. These patients are routinely treated with a FLT3 inhibitor after HCT, but there is limited evidence to support this. Accordingly, we conducted a randomized trial of post-HCT maintenance with the FLT3 inhibitor gilteritinib (ClinicalTrials.gov identifier: NCT02997202) to determine if all such patients benefit or if detection of measurable residual disease (MRD) could identify those who might benefit. METHODS Adults with FLT3-ITD AML in first remission underwent HCT and were randomly assigned to placebo or 120 mg once daily gilteritinib for 24 months after HCT. The primary end point was relapse-free survival (RFS). Secondary end points included overall survival (OS) and the effect of MRD pre- and post-HCT on RFS and OS. RESULTS Three hundred fifty-six participants were randomly assigned post-HCT to receive gilteritinib or placebo. Although RFS was higher in the gilteritinib arm, the difference was not statistically significant (hazard ratio [HR], 0.679 [95% CI, 0.459 to 1.005]; two-sided P = .0518). However, 50.5% of participants had MRD detectable pre- or post-HCT, and, in a prespecified subgroup analysis, gilteritinib was beneficial in this population (HR, 0.515 [95% CI, 0.316 to 0.838]; P = .0065). Those without detectable MRD showed no benefit (HR, 1.213 [95% CI, 0.616 to 2.387]; P = .575). CONCLUSION Although the overall improvement in RFS was not statistically significant, RFS was higher for participants with detectable FLT3-ITD MRD pre- or post-HCT who received gilteritinib treatment. To our knowledge, these data are among the first to support the effectiveness of MRD-based post-HCT therapy.

引用

页码：1766 / 1775

页数：15