Preview

Russian Journal for Personalized Medicine

Advanced search

Еarly splenic response to ruxolitinib correlates with survival: a russian retrospective multicenter study in patients with myelofibrosis

https://doi.org/10.18705/2782-3806-2023-3-3-64-78

Abstract

We retrospectively analyzed the effectiveness of ruxolitinib in patients with myelofibrosis (MF) in real clinical practice in Russia. The study included 42 patients with MF with an average age of 56 years from 10 inpatient and outpatient clinics. The majority of patients (55 %) belonged to the intermediate risk group 1 on the DIPSS scale, 86 % had massive splenomegaly and 88 % had constitutional symptoms. The average initial dose of ruxolitinib was 15 mg twice a day. At the time of analysis, 74 % of patients continued taking ruxolitinib with an average duration of therapy of 20 months. A decrease in the palpable size of the spleen by at least 50 % was recorded in 36 % and 46 % of patients assessed after 3 and 6 months of treatment, respectively. A correlation was found between OV, initial splenomegaly and splenic response after 3 months of therapy. It should be noted that no deaths were recorded in patients with a decrease in the size of the spleen by ≥ 50 %. There were no cases of discontinuation of treatment due to side effects. In general, in our retrospective study, ruxolitinib effectively controlled constitutional symptoms and reduced the size of the spleen in patients with MF. An early splenic response after 3 months of therapy is apparently a prognostic factor for OS, and a decrease in the size of the spleen by less than 25 % should be considered as treatment ineffectiveness in patients with MF taking ruxolitinib.

About the Authors

E. G. Lomaia
Almazov National Medical Research Centre
Russian Federation

Lomaia Elza G., PhD, Head of the Research Institute of Immuno-Oncology, Research Centre for Personalized Medicine

Saint Petersburg



N. T. Siordia
Almazov National Medical Research Centre
Russian Federation

Siordia Nadia T., Hematologist, Department of Chemotherapy of Oncohematological Diseases and Bone Marrow Transplantation No. 2

Saint Petersburg



O. V. Kulemina
Almazov National Medical Research Centre
Russian Federation

Kulemina Olga V., Researcher, Research Institute of Immuno-Oncology, National Center for Personalized Medicine, Hematologist, Department of Chemotherapy of Oncohematological Diseases and Bone Marrow Transplantation No. 2

Saint Petersburg



V. V. Strugov
Almazov National Medical Research Centre
Russian Federation

Strugov Vladimir V., Researcher, Research Laboratory of Oncohematology, Institute of Oncology and Hematology, Hematologist, Department of Chemotherapy of Oncohematological Diseases and Bone Marrow Transplantation No. 2

Saint Petersburg



O. M. Senderova
Irkutsk Regional Clinical Hospital
Russian Federation

Senderova Olga M., PhD, Hematologist, Consultative and diagnostic polyclinic

Irkutsk

 



O. Е. Ochirova
Semashko Republican Clinical Hospital
Russian Federation

Ochirova Oksana Е., Head of the Department of Hematology

Ulan-Ude



E. B. Zhalsanova
Semashko Republican Clinical Hospital
Russian Federation

Zhalsanova Erzhena B., Hematologist, Department of Hematology

Ulan-Ude



A. Yu. Furtovskaya
Almazov National Medical Research Centre
Russian Federation

Furtovskaya Anna Yu., Hematologist, Department of
Chemotherapy of Oncohematological Diseases and Bone
Marrow Transplantation No. 2

Saint Petersburg



Yu. A. Alekseeva
Almazov National Medical Research Centre
Russian Federation

Alekseeva Yulia A., PhD, Head of the Department of Chemotherapy of Oncohematological Diseases and Bone Marrow Transplantation No. 2

Saint Petersburg



N. S.  Lazorko
Almazov National Medical Research Centre
Russian Federation

Lazorko Natalia S., Head of the Department of Specialized Medical Assistance to Oncological Patients of the Consultative and Diagnostic Center

Saint Petersburg



E. I. Sbityakova
Almazov National Medical Research Centre
Russian Federation

Sbityakova Evgenia I., Hematologist, Department of Specialized Medical Assistance to Cancer Patients of the Consultative and Diagnostic Center

Saint Petersburg



G.  P. Dimov
Municipal Clinical Hospital No. 1
Russian Federation

Dimov Georgiy P., PhD, Hematologist, Hematology office

Chelyabinsk



M. G. Pozina
Municipal Clinical Hospital No. 1
Russian Federation

Pozina Marina G., Hematologist

Chelyabinsk



O. Yu. Li
Sakhalin Regional Clinical Hospital
Russian Federation

Li Olga Yu., Hematologist, Department of Hematology

Yuzhno-Sakhalinsk



K. B. Trizna
Tomsk Regional Clinical Hospital
Russian Federation

Trizna Ksenia B., Hematologist, Tomsk Regional Clinical and Diagnostic Polyclinic

Tomsk



M. A. Mikhalev
Krasnoyarsk Interdistrict Clinical Hospital No. 7
Russian Federation

Mikhalev Mikhail A., Hematologist, Department of Hematology and Chemotherapy

Krasnoyarsk



E. V. Sokurova
Vladivostok Polyclinic No. 4
Russian Federation

Sokurova Elena V., Hematologist, Polyclinic Department No. 4

Vladivostok



A. A. Otmorskaya
Regional Clinical Hospital
Russian Federation

Otmorskaya Anna A., Hematologist at the regional consultative polyclinic

Barnaul



A. S. Khazieva
Krasnoyarsk Regional Clinical Hospital
Russian Federation

Khazieva Anna S., Hematologist, Consultative and Diagnostic Polyclinic

Krasnoyarsk



V. V. Ustyantseva
Road Clinical Hospital at station Chelyabinsk JSC “Russian Railways”
Russian Federation

Ustyantseva Victoria V., Hematologist, Polyclinic Department

Chelyabinsk



Yu. D. Matvienko
Almazov National Medical Research Centre
Russian Federation

Matvienko Yulia D., Researcher, Research Institute of Immuno-Oncology, Research Centre for Personalized Medicine

Akkuratova str., 2, Saint Petersburg, 197341

 



A. Yu. Zaritsky
Almazov National Medical Research Centre
Russian Federation

[Zaritsky Andrey Yu.], PhD, former Director of the Institute of Oncology and Hematology

Saint Petersburg



References

1. Tefferi A, Lasho TL, Jimma T, et al. One thousand patients with primary myelofibrosis: the Mayo clinic experience. Mayo Clin. Proc. 2012; 87:25–33. https://doi.org/10.1016/j.mayocp.2011.11.001

2. Cervantes F, Dupriez B, Pereira A, et al. New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood. 2009; 11:2895- 2901. https://doi.org/10.1182/blood-2008-07-170449

3. Patriarca F, Bacigalupo A, Sperotto A, et al. GITMO. Allogeneic hematopoietic stem cell transplantation in myelofibrosis: the 20-year experience of the Gruppo Italiano Trapianto di Midollo Osseo (GITMO). Haematologica. 2008; 93:1514–1522. https:// doi.org/10.3324/haematol.12828

4. Harrison CN, Mesa RA, Kiladjian JJ, et al. Health-related quality of life and symptoms in patients with myelofibrosis treated with ruxolitinib versus best available therapy. Br J Haematol. 2013;162:229–239. https://doi.org/10.1111/bjh.12375

5. Mitra D, Kaye JA, Piecoro LT, et al. Symptom burden and splenomegaly in patients with myelofibrosis in the United States: a retrospective medical record review. Cancer medicine. 2013; 2(6):889–898. https://doi.org/10.1002/cam4.136

6. Čokić VP, Mitrović-Ajtić O, Beleslin-Čokić BB, et al. Proinflammatory Cytokine IL-6 and JAK-STAT Signaling Pathway in Myeloproliferative Neoplasms. Mediators of inflammation (2015). 2015:1–13. https://doi.org/10.1155/2015/453020

7. Quintás-Cardama A, Verstovsek S. Molecular pathways: Jak/STAT pathway: mutations, inhibitors, and resistance. Clinical Cancer Research. 2013; 19:1933– 1940. https://doi.org/10.1158/1078-0432.CCR-12-0284

8. Mesa RA, Verstovsek S, Gupta V, et al. Effects of ruxolitinib treatment on metabolic and nutritional parameters in patients with myelofibrosis from COMFORT-I. Clin Lymphoma Myeloma Leuk. 2015; 15:214–221. https://doi.org/10.1016/j.clml.2014.12.008

9. Tefferi A, Vaidya R, Caramazza D, et al. Circulating interleukin (IL)-8, IL-2R, IL-12, and IL15 levels are independently prognostic in primary myelofibrosis: a comprehensive cytokine profiling study. JCO. 2011; 29:1356–1363. https://doi.org/10.1200/JCO.2010.32.9490

10. Vannucchi AM, Kantarjian HM, Kiladjian JJ, et al. COMFORT Investigators. A pooled analysis of overall survival in COMFORT-I and COMFORT-II, 2 randomized phase III trials of ruxolitinib for the treatment of myelofibrosis. Haematologica. 2015;100:1139–1145. https://doi.org/10.3324/haematol.2014.119545

11. Verstovsek S, Mesa RA, Gotlib J, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012; 366:799–807. https:// doi.org/10.1056/NEJMoa1110557

12. Verstovsek S, Mesa RA, Gotlib J, et al. COMFORT-I investigators. Long-term treatment with ruxolitinib for patients with myelofibrosis: 5-year update from the randomized, double-blind, placebo-controlled, phase 3 COMFORT-I trial. J. Hematol. Oncol. 2017; 10:55. https://doi.org/10.1186/s13045-017-0417-z

13. Tefferi A, Cervantes F, Mesa R, et al. Revised response criteria for myelofibrosis: International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) consensus report. Blood. 2013; 122:1395–1398. https://doi.org/10.1182/blood-2013-03-488098

14. Miller CB, Komrokji RS, Mesa RA, et al. Practical Measures of Clinical Benefit With Ruxolitinib Therapy: An Exploratory Analysis of COMFORT-I. Clin Lymphoma Myeloma Leuk. 2017; 17:479–487. https://doi.org/10.1016/j.clml.2017.05.015

15. JAKAFI® (ruxolitinib) tablets, for oral use Initial U. S. Approval (2011). https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202192s017lbl.pdf (accessed on 27 May 2020)

16. Verstovsek, S, Kantarjian HM, Estrov Z, et al. Long-term outcomes of 107 patients with myelofibrosis receiving JAK1/JAK2 inhibitor ruxolitinib: survival advantage in comparison to matched historical controls. Blood. 2012; 120:1202–1209. https://doi.org/10.1182/blood-2012-02-414631

17. Cervantes F, Pereira A Does ruxolitinib prolong the survival of patients with myelofibrosis? Blood. 2017; 129:832–837. https://doi.org/10.1182/blood-2016-11-731604

18. Palandri F, Palumbo GA, Bonifacio M, et al. Baseline factors associated with response to ruxolitinib: an independent study on 408 patients with myelofibrosis. Oncotarget. 2017; 8:79073–79086. https://doi.org/10.18632/oncotarget.18674

19. Al-Ali HK, Griesshammer M, le Coutre P, et al. Safety and efficacy of ruxolitinib in an open-label, multicenter, single-arm phase 3b expanded-access study in patients with myelofibrosis: a snapshot of 1144 patients in the JUMP trial. Haematologica. 2016; 101:1065–1073. https://doi.org/10.3324/haematol.2016.143677

20. Palandri F, Tiribelli M, Benevolo G, et al. Efficacy and safety of ruxolitinib in intermediate-1 IPSS risk myelofibrosis patients: Results from an independent study. Hematol Oncol. 2018; 36(1):285–290. https://doi.org/10.1002/hon.2429

21. Mead AJ, Milojkovic D, Knapper S, et al. Response to ruxolitinib in patients with intermediate‐1–, intermediate‐2–, and high‐risk myelofibrosis: results of the UK ROBUST Trial. Br J of Haematol. 2015; 170:29–39. https://doi.org/10.1111/bjh.13379

22. Davis KL, Côté I, Kaye JA, et al. Real-World Assessment of Clinical Outcomes in Patients with LowerRisk Myelofibrosis Receiving Treatment with Ruxolitinib. Advances in hematology. 2015; 848473:1–9. https://doi.org/10.1155/2015/848473

23. Talpaz M, Erickson-Viitanen S, Hou K, et al. Evaluation of an alternative ruxolitinib dosing regimen in patients with myelofibrosis: an open-label phase 2 study. Br J Hematol Oncol. 2018; 11:101. https://doi.org/10.1186/s13045-018-0642-0

24. Harrison CN, Schaap N, Vannucchi A, et al. Fedratinib (FEDR) in myelofibrosis (MF) patients previously treated with ruxolitinib (RUX): A reanalysis of the JAKARTA-2 study. J. Clin. Oncol. 2019; 37:7057. https://doi.org/10.1200/JCO.2019.37.15_suppl.7057

25. Vardiman JW, Thiele J, Arber DA, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009; 114:937–951. https://doi.org/10.1182/blood-2009-03-209262

26. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016; 127:2391–2405. https://doi.org/10.1182/blood-2016-03-643544


Review

For citations:


Lomaia E.G., Siordia N.T., Kulemina O.V., Strugov V.V., Senderova O.M., Ochirova O.Е., Zhalsanova E.B., Furtovskaya A.Yu., Alekseeva Yu.A., Lazorko N.S., Sbityakova E.I., Dimov G.P., Pozina M.G., Li O.Yu., Trizna K.B., Mikhalev M.A., Sokurova E.V., Otmorskaya A.A., Khazieva A.S., Ustyantseva V.V., Matvienko Yu.D., Zaritsky A.Yu. Еarly splenic response to ruxolitinib correlates with survival: a russian retrospective multicenter study in patients with myelofibrosis. Russian Journal for Personalized Medicine. 2023;3(3):64-78. (In Russ.) https://doi.org/10.18705/2782-3806-2023-3-3-64-78

Views: 527


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2782-3806 (Print)
ISSN 2782-3814 (Online)