The results of a study on the effectiveness 37 and safety of treatment with vemurafenib and cytarabine/2-chloro-2′-deoxyadenosine combination in patients with Langerhans cell histiocytosis with BRAFV600E mutation

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Abstract

   Here, we report on a new treatment protocol for patients with BRAF-positive Langerhans cell histiocytosis (LCH). To achieve remission in the affected patients, we used vemurafenib (a targeted drug) in combination with cytarabine (Ara-C) and cladribine (2-CdA). The study included 27 patients: 18 children with multisystem LCH with risk organ involvement (RO+) and 9 – with multisystem LCH without risk organ involvement (RO–). The treatment started with a 28-day cycle of vemurafenib, with subsequent discontinuation. On Day 29, Аra-C + 2-СdA chemotherapy cycle № 1 was initiated. Vemurafenib treatment was again started on Day +1 after the Ara-C + 2-CdA cycle. The interval between the cycles was 28 days. Similarly, the next two Аra-C + 2-СdA chemotherapy cycles (№ 2 and № 3) were carried out. Then therapy with vemurafenib was stopped and 3 cycles of 2-CdA were administered. All the patients responded to the treatment quickly: on Day 28, disease activity score decreased from 15 to 2 in the RO+ group and from 4 to 0 in the RO– group. The two-year relapse-free survival in the RO+ group was 82 % (95 % confidence interval 66–100), and 89 % (95 % confidence interval 71–100) in the RO– patients. The overall survival in both groups was 100 %. Our study demonstrates the safety and effectiveness of the treatment with vemurafenib and intermediate-dose 2-CdA and Ara-C in children with multisystem RO+ and refractory LCH. This prospective non-randomized multicenter study was approved by the Independent Ethics Committee (Minutes No. 3e/1-18) and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation. It is registered at clinicaltrials.gov under the number NCT03585686. The first patient was enrolled on 22 June 2018, the data collection was stopped on 30 April 2023.

About the authors

E. I. Lyudovskikh

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

Author for correspondence.
Email: evcola@yandex.ru
ORCID iD: 0000-0003-0717-2019

Evelina I. Lyudovskikh, a pediatric oncologist

Department of Hematopoietic Stem Cell Transplantation № 2

117997; 1 Samory Mashela St.; Moscow

Russian Federation

D. A. Yevseyev

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

Email: dmitry.evseev@fccho-moscow.ru
ORCID iD: 0000-0001-8610-0624

Moscow

Russian Federation

D. S. Osipova

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

Email: d_ossipova@mail.ru
ORCID iD: 0000-0002-9968-9332

Moscow

Russian Federation

E. V. Raykina

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

Email: Elena.Raykina@fccho-moscow.ru
ORCID iD: 0000-0002-7634-2053

Moscow

Russian Federation

I. I. Kalinina

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

Email: Irina.Kalinina@fccho-moscow.ru
ORCID iD: 0000-0002-0813-5626

Moscow

Russian Federation

D. D. Baydildina

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

Email: Dina.Baydildina@fccho-moscow.ru
ORCID iD: 0000-0001-7130-8596

Moscow

Russian Federation

A. M. Popov

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

Email: alexandr.popov@fccho-moscow.ru
ORCID iD: 0000-0002-0889-6986

Moscow

Russian Federation

E. A. Burtsev

The Morozov Children's City Clinical Hospital of the Department of Health of Moscow

Email: i@eburtsev.ru
ORCID iD: 0000-0002-3623-6547

Moscow

Russian Federation

G. O. Bronin

The Morozov Children's City Clinical Hospital of the Department of Health of Moscow

Email: mdgkb@zdrav.mos.ru
ORCID iD: 0000-0002-0694-3996

Moscow

Russian Federation

O. S. Fink

Russian Children's Clinical Hospital of the N.I. Pirogov Russian National Research Medical University of Ministry of Healthcare of the Russian Federation

Email: clinika@rdkb.ru
ORCID iD: 0000-0003-1336-9379

Moscow

Russian Federation

B. B. Purbuyeva

Russian Children's Clinical Hospital of the N.I. Pirogov Russian National Research Medical University of Ministry of Healthcare of the Russian Federation

Email: clinika@rdkb.ru
ORCID iD: 0000-0003-3698-4462

Moscow

Russian Federation

E. A. Pristanskova

Russian Children's Clinical Hospital of the N.I. Pirogov Russian National Research Medical University of Ministry of Healthcare of the Russian Federation

Email: clinika@rdkb.ru
ORCID iD: 0000-0002-4569-657X

Moscow

Russian Federation

A. A. Maschan

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

Email: Aleksey.Maschan@fccho-moscow.ru
ORCID iD: 0000-0002-0016-6698

Moscow

Russian Federation

M. A. Maschan

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

Email: Michael.Maschan@fccho-moscow.ru
ORCID iD: 0000-0003-1735-0093

Moscow

Russian Federation

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Copyright (c) 2023 Lyudovskikh E.I., Yevseyev D.A., Osipova D.S., Raykina E.V., Kalinina I.I., Baydildina D.D., Popov A.M., Burtsev E.A., Bronin G.O., Fink O.S., Purbuyeva B.B., Pristanskova E.A., Maschan A.A., Maschan M.A.

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