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199406, Санкт-Петербург, ул.Гаванская, д. 49, корп.2

ISSN 1999-6314

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«
Vol. 22, Art. 6 (pp. 74-98)    |    2021       
»

The efficacy of front-line chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab (fcr) in patients with chronic lymphocytic leukemia in real clinical practice.
Kataeva E., Klinushkina E., Golenkov A., Chuksina Yu., Mitina T., Zakharov S., Trifonova E., Chernykh Yu.,Visotskaya L., Belousov K., Vardanyan R., Kharasova Z., Boginskaya E.

SBUZ MO MONIKI im. M. F. Vladimirsky



Brief summary

The aim of the study was to investigate the clinical efficacy of front-line FCR program treatment in CLL patients within a clinical model integrated into real practice. Design and Methods. The study included 108 previously untreated patients with CD20-positive chronic lymphocytic leukemia. The stage of the disease was assessed according to the Rai classification, the functional state was determined on the ECOG scale, and the comorbidity was assessed on the SIRS - G scale. The 17p13/TP53 deletion was calculated using the FISH method, and the IGHV-status observed through PCR. The FCR program consisting of 6 standard courses was being conducted over a longer period of time, which extended the induction period and reduced treatment density. Minimal residual disease (MRD) was assessed according to the international standardized protocol (Rawstron, 2007) by 4-color flow cytometry. Some patients were receiving maintenance treatment with Rituximab for 2 years, compared to the group of patients without maintenance therapy. The main control points of the analysis were PFS and OS. The OS was evaluated according to the intent-to-treat principle. Results. The clinical efficacy of the treatment was evaluated according to the iWCLL 2008. The overall response rate was 92.6%, complete remission(CR) was detected in 53.9%. 52.8% patients had undetectable MRD (UMRD) in the peripheral blood and 39.3% patients had UMRD in the bone marrow. The Me follow-up was of 51 months (range 8-150). The Me of PFS from the beginning of FCR induction was 42 months. PFS was significantly longer in patients who achieved CR (p=0,0001), with comorbidity in patients below 5 points (p=0,02), and with achievement of UMRD (p=0,002). Reduced treatment density and maintenance therapy with Rituximab did not affect the duration of PFS. OS from the beginning of FCR-induction was 120 months in 60% of patients. Conclusion. The study showed that the decrease in the density of the FCR program induction in real clinical practice in patients with CLL was accompanied by high efficacy and did not lead to a significant decrease in the PFS compared to patients who received the standard program.


Key words

chronic lymphocytic leukemia, chemoimmunotherapy, FCR, immunophenotyping, minimal residual disease, real practice





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Reference list

1. Rai KR, Peterson BZ, Applebaum F et al. Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N.Engle. J.Med 2000,343: 1750-57.


2. Bessmelcev S.S. Flydarabin v terapii bolnih hronicheskim limfoleikozom. Medicina 2006 (4): 92-101


3. Hallek M, Fisher K, Fingerle-Rowson Y et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukemia a randomized open-label:phase 3 trial. Lancet 2010, 376 (9747): 1164-1174.


4. Fischer K, Bahlo J, Fink AM, Goede V, Herling CD, Cramer P, Langerbeins P, von Tresckow J, Engelke A, Maurer C, Kovacs G, Herling M, Tausch E, Kreuzer KA, Eichhorst B, Böttcher S, Seymour JF, Ghia P, Marlton P, Kneba M, Wendtner CM, Döhner H, Stilgenbauer S, Hallek M.Fischer K, et al. Long-term remissions after FCR chemoimmunotherapy in previously untreated patients with CLL: updated results of the CLL8 trial. Blood. 2016; 127 (2): 208-15.


5. Shanafelt T.D. Wang X.V, Kay N.E. et al. Ibrutinib-rituximab or chemoimmunotherapy for chronic lymphocytic leukemia. N Engl J Med. 2019; Aug 1; 381 (5): 432-443.


6. Woyach J.A, Ruppert AS, Heerema NA et al. Ibrutinib regimens versus chemoimmunotherapy in older patients with antreated CLL. N. Engl J Med. 2018,379(26)2517-25.


7. Seymour j.F, Kippsi j, Eichhorst B et al. Venetoklax, rituximab in relapsed or refractory Chronic Lymphocytic leukemia. N. Engle j Med 2018,378 (12); 1107-1120.


8. Chanan-Khan A, Cramer P, Demirkan F et al. Ibrutinib combined with bendamustine and rituximab compared with placebo, bendamustine and rituximab for preriously treated chronic lymphocytic leukemia or small lymphocytic lymphoma (HELIOS): a randomised, dauble-blind, phase 3 study. Lancet oncol 2016,17(2) 200-211.


9. Zelenetz AD, Barrientos jC, Brow JR et al. Idelaliseb or placelo in combination with bendamustine and rituximab in patients with relapsed or cefractory chronic lymphocytic leukemia: interim zesicts from phase randomised, dencle-blind, phlacebo-centrolledtial Zancet uncol. 2017,18 (3) 297-311.


10. Firstenam M, Hallen M, Eichhorst B. Sequentral and combination treatments with novel agents in chronic lymphocytic leukemia. Hematologica 2019 104 (II): 2144-2154.


11. Sylvan SE, Asklid A, Johansson H et al. First-line therapy in chronic lymphocytic leukemia a Swedish nation-wide real- world study on 1053 consecutive patients treated between 2007 and 2013. Haematologica 2019; 104(4):797-804 https://doi.org/10.3324/haematol.2018.200204


12. Klinicheskie rekomendacii. Hronicheskii limfocitarnii leikoz / limfoma iz malih limfocitov. Odobreno Naychno-prakticheskim Sovetom Minzdrava RF :.2020 // ID:134/1 http://cr.rosminzdrav.ru/schema/134


13. Golenkov A.K., Bessmelcev S.S. Koncepciya klinicheskih issledovanii, integrirovannih v realnyu klinicheskyu praktiky. Vestnik gematologii 2020 XVI 1 str 6-14


14. Hallek M, Cheson BD, Catovsky D. et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute -Working Group 1996 guidelines. Blood. 2008; 111: 5446-56.


15. Hallek M, Cheson BD, Catovsky Detal. IWCLL guidelines for diagnosis, indication for treatment, response assessment, and supportive management of all. Blood.2018;131 (25):2745-2760


16. De Groot V, Beekerman H, Lankhorst G. How to measure comorbidity: a critical review of available methods. J Clin Epidemiol. 2003, v 56, N3, p 221-229.


17. Rawstron, A.C., et al., International standardized approach for flow cytometric residual disease monitoring in chronic lymphocytic leukaemia. Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K, 2007. 21(5): p. 956-64.]


18. Loken MR, Chu SC, Fritschle W, Kalnoski M., Wells DA. Normalization of bone marrow aspirates for hemodilution in flow cytometric analyses. Cytometry B Clin. Cytom. 2008; 76B: 27-36


19. Del Giudice I., Raponi S., Della Starza I., De Propris M.S., Cavalli M., De Novi L. A., Cappelli L.V., Ilari C., Cafforio L., Guarini A. and Foà R. Minimal Residual Disease in Chronic Lymphocytic Leukemia: A New Goal? Frontiers in Oncology | www.frontiersin.org August 2019, Vol. 9, Article 689 P. 1-15 doi: 10.3389/fonc.2019.00689


20. Garcia-Marco J. A., Jimenez J. L., Recasens V., Zarzoso M. F., et all. High prognostic value of measurable residual disease detection by flow cytometry in chronic lymphocytic leukemia patients treated with front-line fludarabine, cyclophosphamide, and rituximab, followed by three years of rituximab maintenance. Haematologica, 2019, 104 (11): 2249-2257; doi:10.3324/haematol.2018.204891


21. Rasi S, Monti S, Spina V, Foa R, Gaidano G, Rossi D. Analysis of NOTCH1 mutations in monoclonal B-cell lymphocytosis. Haematologica 2012; 97(1): 153-154


22. Rossi D, Bruscaggin A, SpinaV, Rasi S, Khiabanian H, Messina M et al. Mutations of the SF3B1 splicing factor in chronic lymphocitic leukemia: association with progression and fludarabine-refractoriness. Blood. 2011; 118: 6904-08.


23. Bouvet E., Borel C., Obéric L., Compaci G., Cazin B., Michallet A.-S., Laurent G., and Ysebaert L. Impact of dose intensity on outcome of fludarabine, cyclophosphamide, and rituximab regimen given in the first-line therapy for chronic lymphocytic leukemia Haematologica, 2013: 98 (1) P. 65-70 doi:10.3324/haematol.2012.070755


24. Fischer K, Bahlo J, Fink AM, et al. Longterm remissions after FCR chemoimmunotherapy


in previously untreated patients with CLL: updated results of the CLL8 trial. Blood. 2016;127(2):208-215.


25. Rossi D, Terzi-di-Bergamo L, De Paoli L, et al. Molecular prediction of durable remission


after first-line fludarabine-cyclophosphamide- rituximab in chronic lymphocytic leukemia. Blood. 2015;126(16):1921-1924.


26. Sorokina T.V., Goryacheva S.R., Spirina V.A., Al-Radi L.S., Obyhova T.N., Biderman B.V., Moiseeva T.N.Medicinskii sovet. 2017, ?6,s. 132-38.


27. Nikitin E.A., Dmitrieva E.A., Panteleev M.A., Emelina E.I. i dr. Ibrytinib v lechenii refrakternogo hronicheskogo limfoleikoza. Klinicheskaya onkogematologiya. 2017, tom 10, ?3,s. 271-81.


28. Stadnik E.A., Timofeeva N.S., Strygov V.V., Zarickii A.U. Ibrytinib v lechenii recidivov hronicheskogo limfoleikoza. Klinicheskaya onkogematologiya. 2018, tom 11, ?1,s. 42-49.


29. Böttcher S, Ritgen M, Fischer K, et al. Minimal residual disease quantification is an independent predictor of progression free and overall survival in chronic lymphocytic


leukemia: a multivariate analysis from the randomized GCLLSG CLL8 trial. J Clin Oncol. 2012;30(9):980-988.





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