Efficacy and Safety of Midostaurin Combined with Chemotherapy in Newly Diagnosed Acute Myeloid Leukemia with FLT3 Mutation

AUTOIMMUNE THROMBOCYTOPENIA ,

SN Bondarenko1, AG Smirnova1, BI Ayubova1, EV Karyagina2, OS Uspenskaya3, YuS Neredko4, AP Kochergina5, IA Samorodova6, EA Pashneva7, YuS Chernykh8, YuA Dunaev9, NB Esef’eva10, RK Il’yasov11, TI Brazhkina12, IA Novokreshchenova13, ZK Simavonyan14, EI Kuzub15, VI Bakhtina16, TI Olkhovich17, MV Burundukova18, EV Babenko1, YuD Oleinikova1, IM Barkhatov1, TL Gindina1, IS Moiseev1, AD Kulagin1

1 RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation; IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo ul., Saint Petersburg, Russian Federation, 197022

2 Municipal Hospital No. 15, 4 Avangardnaya ul., Saint Petersburg, Russian Federation, 198205

3 Leningrad Regional Clinical Hospital, 45 korp. 2A Lunacharskogo pr-t, Saint Petersburg, Russian Federation, 194291

4 Stavropol Krai Clinical Oncology Dispensary, 182a Oktyabrskaya ul., Stavropol, Russian Federation, 355047

5 Krai Clinical Hospital, 1 Lyapidevskogo ul., Barnaul, Russian Federation, 656024

6 Municipal Clinical Hospital No. 31, 3 Dinamo pr-t, Saint Petersburg, Russian Federation, 197110

7 Volgograd Regional Clinical Oncology Dispensary, 78 Zemlyachki ul., Volgograd, Russian Federation, 400138

8 MF Vladimirskii Moscow Regional Research Clinical Institute, 61/2 Shchepkina ul., Moscow, Russian Federation, 129110

9 Arkhangelsk Regional Clinical Hospital, 292 Lomonosova pr-t, Arkhangelsk, Russian Federation, 163045

10 Ulyanovsk Regional Clinical Hospital, 7 III Internatsionala ul., Ulyanovsk, Russian Federation, 432017

11 VM Efetov Crimea Republican Clinical Oncology Dispensary, 49A Bespalova ul., Simferopol, Russian Federation, 295007

12 Ivanovo Regional Clinical Hospital, 1 Lyubimova ul., Ivanovo, Russian Federation, 153040

13 RZhD-Meditsina Clinical Hospital, 15 1-i Krasnoflotskii per., Smolensk, Russian Federation, 214025

14 AI Burnazyan Federal Medical Biophysical Center, 23 Marshala Novikova ul., Moscow, Russian Federation, 123098

15 Rostov State Medical University Hospital, 29 Nakhichevanskii per., Rostov-on-Don, Russian Federation, 344022

16 Krasnoyarsk Krai Clinical Hospital, 3A Partizana Zheleznyaka ul., Krasnoyarsk, Russian Federation, 660022

17 Krasnoyarsk Interdistrict Clinical Hospital No. 7, 4 Akademika Pavlova ul., Krasnoyarsk, Russian Federation, 660003

18 Municipal Clinical Hospital No. 2, 21 Polzunova ul., Novosibirsk, Russian Federation, 630051

For correspondence: Sergei Nikolaevich Bondarenko, MD, PhD, 6/8 L’va Tolstogo ul., Saint Petersburg, Russian Federation, 197022; Tel.: +7(921)994-35-70; e-mail: dr.sergeybondarenko@gmail.com

For citation: Bondarenko SN, Smirnova AG, Ayubova BI, et al. Efficacy and Safety of Midostaurin Combined with Chemotherapy in Newly Diagnosed Acute Myeloid Leukemia with FLT3 Mutation. Clinical oncohematology. 2022;15(2):167–75. (In Russ).

DOI: 10.21320/2500-2139-2022-15-2-167-175

ABSTRACT

Background. The detection of FLT3-ITD mutation in acute myeloid leukemia (AML) patients is associated with poor prognosis and is an indication for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the first remission. Midostaurin is the first FLT3 inhibitor approved for the treatment of AML patients with FLT3 mutation in the Russian Federation in November 2019. This study deals with the initial experiences of using midostaurin in several centers for hematology in the Russian Federation.

Aim. To analyze the initial experiences of using midostaurin at different AML stages.

Materials & Methods. The study enrolled 42 patients with newly diagnosed AML with FLT3 mutation, who were treated with midostaurin combined with chemotherapy. Allo-HSCT was performed in 11 patients.

Results. The 2-year overall survival (OS) was 51 %, and the 2-year event-free survival (EFS) was 45 %. After achieving remission, the 2-year disease-free survival (DFS) was 58 %. The 1-year DFS of allo-HSCT recipients was 86 % (95% confidence interval [95% CI] 60–100 %) vs. 66 % in patients treated with chemotherapy without allo-HSCT (95% CI 34–98 %), respectively (p = 0.5). Hyperleukocytosis at disease onset was associated with high relapse risk. Midostaurin had to be discontinued in 5 % of cases due to atrial fibrillation and QTc prolongation.

Conclusion. The present study demonstrates the safety and importance of including midostaurin in the regimens for treating AML with FLT3 mutation. Midostaurin assignment for maintenance therapy, after allo-HSCT as well as without performing it, can result in considerable improvement of OS and DFS.

Keywords: acute myeloid leukemias, FLT3 mutations, targeted therapy, midostaurin.

Received: December 27, 2021

Accepted: March 20, 2022

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Статистика Plumx английский

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