Efficacy Predictors of the Third-Line Tyrosine Kinase Inhibitor Therapy in Patients with Chronic Phase of Chronic Myeloid Leukemia: Results of a Multi-Center Study

EG Lomaia1, VA Shuvaev2,3, TV Chitanava1, YuD Matvienko1, IS Martynkevich2, SV Voloshin2, EV Efremova2, ES Mileeva2, MS Fominykh4, AE Kersilova3, EV Karyagina5, NV Il’ina5, NV Dorofeeva6, NV Medvedeva6, AV Klimovich6, TV Shneider7, SA Stepanova7, NF Polezhaikovskaya7, NT Siordiya1, EI Sbityakova1, NS Lazorko1, EN Tochenaya1, DV Motorin1, NA Shnalieva1, YuA Alekseeva1, DB Zammoeva1, AYu Zaritskey1

1 VA Almazov National Medical Research Center, 2 Akkuratova ul., Saint Petersburg, Russian Federation, 197341

2 Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya ul., Saint Petersburg, Russian Federation, 191024

3 VV Veresaev Municipal Clinical Hospital, 10 Lobnenskaya ul., Moscow, Russian Federation, 127644

4 AVA-PETER, Multispecialty Clinic “Skandinaviya”, 55A Liteinyi pr-t, Saint Petersburg, Russian Federation, 191014

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

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

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

For correspondence: Tamara Vangelevna Chitanava, 2 Akkuratova ul., Saint Petersburg, Russian Federation, 197341; e-mail: chitanava.tamara@yandex.ru

For citation: Lomaia EG, Shuvaev VA, Chitanava TV, et al. Efficacy Predictors of the Third-Line Tyrosine Kinase Inhibitor Therapy in Patients with Chronic Phase of Chronic Myeloid Leukemia: Results of a Multi-Center Study. Clinical oncohematology. 2022;15(3):271–81. (In Russ).

DOI: 10.21320/2500-2139-2022-15-3-271-281


Background. The introduction of tyrosine kinase inhibitors (TKIs) into real-world clinical practice considerably improved the prognosis for patients with chronic myeloid leukemia (CML). However, during long-term follow-up, almost 1/2 and 2/3 of patients in the chronic phase (CP) discontinue TKI therapy of the first or second line, respectively. According to the Russian and International clinical guidelines, the third-line therapy should include allogeneic hematopoietic stem cell transplantation (allo-HSCT). And yet, some patients on the third-line therapy achieve and sustain optimal response on long-term TKI administration. Up to now, no clear-cut prognostic factors of TKI efficacy in the third-line therapy have been identified. This creates a challenge for treatment decision making after the failures of two lines of TKI therapy.

Aim. To assess the efficacy of the third-line TKI therapy in real-world clinical practice and to identify the factors affecting the long-term therapy outcomes in CML-CP.

Materials & Methods. The retrospective study enrolled 73 CML-CP patients aged ≥ 18 years, treated with TKIs in the third-line at 5 specialized institutions in Saint Petersburg and Leningrad Region. Among the patients there were 26 men (35 %). The median age of the patients was 51 years (range 25–88 years).

Results. With the median (range) third-line TKI therapy duration of 14 (1–120) months, the rate of complete cytogenetic response (CCR) was 30 % (n = 22) in the total cohort. The median time before achieving CCR was 9 (4–25) months. With the median follow-up time from the beginning of third-line TKI therapy till the last visit of 25 (3–136) months, progression to accelerated phase or blast crisis was observed only in 13 (17 %) out of 73 patients. Death was reported in 26 % (n = 19) of cases, among them 5 patients whose death was not CML-associated. At the last visit, 13/73 (18 %) patients were still on third-line TKI therapy. Direct and long-term therapy outcomes, including achievement of CCR and assessment of overall and progression-free survivals, were significantly better in patients with any cytogenetic response (CR) than in those without it or without complete hematologic response.

Conclusion. The implementation of TKIs in the third-line CML-CP therapy seems to be suitable for patients with at least some CR, especially if an optimal donor of hematopoietic stem cells is unavailable or if the risk of severe allo-HSCT complications is too high.

Keywords: chronic myeloid leukemia, chronic phase, complete cytogenetic response, tyrosine kinase inhibitors, third-line therapy, allogeneic hematopoietic stem cell transplantation, minimal residual disease.

Received: April 7, 2022

Accepted: June 20, 2022

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