Background: Different studies analyzed the outcome of patients (pts) who discontinued tyrosine kinase inhibitors (TKIs) reporting a median treatment-free remission (TFR) rate of 55%. On these bases it is judged safe to discontinue treatment in experimental contexts. Aims: To evaluate TFR in the setting of clinical practice. Methods: We retrospectively collected and analyzed the outcome of pts treated in 32 Divisions of Hematology in Italy, who discontinued TKIs in CMR. Results: We analyzed a total of 292 pts who discontinued TKIs. Median age at stop was 59 yrs (IQR, 47; 70). 160 (55%) were male; 58%, 31% and 11% were low, intermediate and high Sokal score respectively. 161 pts (55%) discontinued in first line; 117 pts (40%) in second, 13 pts (5%) in third, and 1 pt in fourth line. 210 pts (72%) were on treatment with imatinib, 28% with either nilotinib (58), dasatinib (23), bosutinib (1) at the time of discontinuation. Median duration of treatment with the last TKI was 77 mos (IQR 54; 111), median duration of CMR was 46 mos (IQR 31; 74). At 3 mos of last TKI 34% of pts were in MMR, 25% were in PCyR and/or had a transcript < 10%, 40% were in CCyR and/or had a transcript < 1%, and 1% had no response. Responses at discontinuation were: 35% MR4, 31% MR4.5, 18% MR5. 16% were defined as “undetectable”. Reasons for discontinuation were: toxicity for 20% of pts, pregnancy for 6%, pt request for 62%, enrollment in ISAV protocol for 12%. After a median follow-up of 34 mos (IQR 23.5; 53.2) estimated TFR was 62% (95%CI 56; 67.6). Reasons for restarting were: loss of MR4 for 19% of pts, loss of MR3 for 69%, loss of CCyR for 9%, other reasons for 3%. Median time to restart treatment was 6 mos (IQR: 4; 11). We assessed age, sex, Sokal score, type of transcript, previous IFN therapy, duration of TKI therapy, response at 3 mos, time to CMR, CMR duration, line of therapy, depth of MR, reasons for stop as potential prognostic factors for TFR, but no statistically significant association were found, with the exception of age: a decreased risk in older vs younger pts. Pts who restarted therapy were treated with imatinib (77), nilotinib (22), dasatinib (9), bosutinib (3) or ponatinib (1). All of them regained at least MR3, with the exception of 7 not reported and 10 with no MMR. No pts progressed. Conclusion: Although our study have the limitation of a restrospective study, our experience confirms that discontinuation of TKIs is feasible and safe in the clinical practice.
Tyrosine kinase inhibitors discontinuation in chronic myeloid leukemia: a retrospective analysis of 208 italian patients / C. Fava, G. Rege-Cambrin, I. Dogliotti, P. Berchialla, M. Cerrano, G. Rosti, F. Castagnetti, G. Gugliotta, B. Martino, C. Gambacorti-Passerini, E. Abruzzese, E. Orlandi, E. Chiara, P. Pregno, A. Gozzini, P. Avanzini, M. Bergamaschi, M. Crugnola, M. Bocchia, S. Galimberti, D. Rapezzi, A. Iurlo, D. Cattaneo, R. Latagliata, M. Breccia, M. Cedrone, M. Santoro, M. Annunziata, L. Levato, F. Stagno, F. Cavazzini, N. Sgherza, G. Catania, L. Luciano, S. Russo, P. Musto, G. Caocci, F. Sorà, F. Iuliano, F. Lunghi, G. Specchia, M. Baccarani, D. Ferrero, G. Saglio. - In: HAEMATOLOGICA. - ISSN 0390-6078. - 102:suppl. 3(2017), pp. 84-84. (Intervento presentato al 46. convegno Congress of the Italian Society of Hematology tenutosi a Roma nel 2017).
Tyrosine kinase inhibitors discontinuation in chronic myeloid leukemia: a retrospective analysis of 208 italian patients
D. Cattaneo;
2017
Abstract
Background: Different studies analyzed the outcome of patients (pts) who discontinued tyrosine kinase inhibitors (TKIs) reporting a median treatment-free remission (TFR) rate of 55%. On these bases it is judged safe to discontinue treatment in experimental contexts. Aims: To evaluate TFR in the setting of clinical practice. Methods: We retrospectively collected and analyzed the outcome of pts treated in 32 Divisions of Hematology in Italy, who discontinued TKIs in CMR. Results: We analyzed a total of 292 pts who discontinued TKIs. Median age at stop was 59 yrs (IQR, 47; 70). 160 (55%) were male; 58%, 31% and 11% were low, intermediate and high Sokal score respectively. 161 pts (55%) discontinued in first line; 117 pts (40%) in second, 13 pts (5%) in third, and 1 pt in fourth line. 210 pts (72%) were on treatment with imatinib, 28% with either nilotinib (58), dasatinib (23), bosutinib (1) at the time of discontinuation. Median duration of treatment with the last TKI was 77 mos (IQR 54; 111), median duration of CMR was 46 mos (IQR 31; 74). At 3 mos of last TKI 34% of pts were in MMR, 25% were in PCyR and/or had a transcript < 10%, 40% were in CCyR and/or had a transcript < 1%, and 1% had no response. Responses at discontinuation were: 35% MR4, 31% MR4.5, 18% MR5. 16% were defined as “undetectable”. Reasons for discontinuation were: toxicity for 20% of pts, pregnancy for 6%, pt request for 62%, enrollment in ISAV protocol for 12%. After a median follow-up of 34 mos (IQR 23.5; 53.2) estimated TFR was 62% (95%CI 56; 67.6). Reasons for restarting were: loss of MR4 for 19% of pts, loss of MR3 for 69%, loss of CCyR for 9%, other reasons for 3%. Median time to restart treatment was 6 mos (IQR: 4; 11). We assessed age, sex, Sokal score, type of transcript, previous IFN therapy, duration of TKI therapy, response at 3 mos, time to CMR, CMR duration, line of therapy, depth of MR, reasons for stop as potential prognostic factors for TFR, but no statistically significant association were found, with the exception of age: a decreased risk in older vs younger pts. Pts who restarted therapy were treated with imatinib (77), nilotinib (22), dasatinib (9), bosutinib (3) or ponatinib (1). All of them regained at least MR3, with the exception of 7 not reported and 10 with no MMR. No pts progressed. Conclusion: Although our study have the limitation of a restrospective study, our experience confirms that discontinuation of TKIs is feasible and safe in the clinical practice.File | Dimensione | Formato | |
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