Background Imatinib slows development of chronic myeloid leukemia (CML). However, available information on morbidity and mortality is largely based on sponsored trials, whereas independent long-term field studies are lacking. Patients and Methods Consecutive CML patients who started imatinib treatment before 2005 and who were in complete cytogenetic remission (CCyR) after 2 years (+/- 3 months) were eligible for enrollment in the independent multicenter Imatinib Long-Term (Side) Effects (ILTE) study. Incidence of the first serious and nonserious adverse events and loss of CCyR were estimated according to the Kaplan-Meier method and compared with the standard log-rank test. Attainment of negative Philadelphia chromosome hematopoiesis was assessed with cytogenetics and quantitative polymerase chain reaction. Cumulative incidence of death related or unrelated to CML progression was estimated, accounting for competing risks, according to the Kalbleisch-Prentice method. Standardized incidence ratios were calculated based on population rates specific for sex and age classes. Confidence intervals were calculated by the exact method based on the chi(2) distribution. All statistical tests were two-sided. Results A total of 832 patients who were treated for a median of 5.8 years were enrolled. There were 139 recorded serious adverse events, of which 19.4% were imatinib-related. A total of 830 nonserious adverse events were observed in 53% of patients; 560 (68%) were imatinib-related. The most frequent were muscle cramps, asthenia, edema, skin fragility, diarrhea, tendon, or ligament lesions. Nineteen patients (2.3%) discontinued imatinib because of drug-related toxic effects. Forty-five patients lost CCyR, at a rate of 1.4 per 100 person-years. Durable (> 1 year) negative Philadelphia chromosome hematopoiesis was attained by 179 patients. Twenty deaths were observed, with a 4.8% mortality incidence rate (standardized incidence ratio = 0.7; 95% confidence interval = 0.40 to 1.10, P = .08), with only six (30%) associated with CML progression. Conclusions In this study, CML-related deaths were uncommon in CML patients who were in CCyR 2 years after starting imatinib, and survival was not statistically significantly different from that of the general population.

Multicenter independent assassment of outcomes in chronic myeloid leukemia patients treated with imatinib / C.Gambacorti-Passerini ; L.Antolini ; FX.Mahon ; F. Guilhot; M. Deininger ; C. Fava; A. Nagler CM.Della Casa ;E. Morra ; E.Abruzzese ; A.D'Emilio ; F.Stagno ; P.le Coutre ; R. Hurtado-Monroy ; V. Santini;B. Martino; F. Pane; F. Piccin; P.Giraldo ; S.Assouline ; MA.Durosinmi ; O.Leeksma ; EM.Pogliani ; M.Puttini ; E.Jang ; J.Reiffers ; MG.Valsecchi ;DW. Kim. - In: JOURNAL OF THE NATIONAL CANCER INSTITUTE. - ISSN 0027-8874. - STAMPA. - 103:(2011), pp. 553-561. [10.1093/jnci/djr060]

Multicenter independent assassment of outcomes in chronic myeloid leukemia patients treated with imatinib

SANTINI, VALERIA;
2011

Abstract

Background Imatinib slows development of chronic myeloid leukemia (CML). However, available information on morbidity and mortality is largely based on sponsored trials, whereas independent long-term field studies are lacking. Patients and Methods Consecutive CML patients who started imatinib treatment before 2005 and who were in complete cytogenetic remission (CCyR) after 2 years (+/- 3 months) were eligible for enrollment in the independent multicenter Imatinib Long-Term (Side) Effects (ILTE) study. Incidence of the first serious and nonserious adverse events and loss of CCyR were estimated according to the Kaplan-Meier method and compared with the standard log-rank test. Attainment of negative Philadelphia chromosome hematopoiesis was assessed with cytogenetics and quantitative polymerase chain reaction. Cumulative incidence of death related or unrelated to CML progression was estimated, accounting for competing risks, according to the Kalbleisch-Prentice method. Standardized incidence ratios were calculated based on population rates specific for sex and age classes. Confidence intervals were calculated by the exact method based on the chi(2) distribution. All statistical tests were two-sided. Results A total of 832 patients who were treated for a median of 5.8 years were enrolled. There were 139 recorded serious adverse events, of which 19.4% were imatinib-related. A total of 830 nonserious adverse events were observed in 53% of patients; 560 (68%) were imatinib-related. The most frequent were muscle cramps, asthenia, edema, skin fragility, diarrhea, tendon, or ligament lesions. Nineteen patients (2.3%) discontinued imatinib because of drug-related toxic effects. Forty-five patients lost CCyR, at a rate of 1.4 per 100 person-years. Durable (> 1 year) negative Philadelphia chromosome hematopoiesis was attained by 179 patients. Twenty deaths were observed, with a 4.8% mortality incidence rate (standardized incidence ratio = 0.7; 95% confidence interval = 0.40 to 1.10, P = .08), with only six (30%) associated with CML progression. Conclusions In this study, CML-related deaths were uncommon in CML patients who were in CCyR 2 years after starting imatinib, and survival was not statistically significantly different from that of the general population.
2011
103
553
561
C.Gambacorti-Passerini ; L.Antolini ; FX.Mahon ; F. Guilhot; M. Deininger ; C. Fava; A. Nagler CM.Della Casa ;E. Morra ; E.Abruzzese ; A.D'Emilio ; F.Stagno ; P.le Coutre ; R. Hurtado-Monroy ; V. Santini;B. Martino; F. Pane; F. Piccin; P.Giraldo ; S.Assouline ; MA.Durosinmi ; O.Leeksma ; EM.Pogliani ; M.Puttini ; E.Jang ; J.Reiffers ; MG.Valsecchi ;DW. Kim
File in questo prodotto:
File Dimensione Formato  
JNCI J Natl Cancer Inst-2011-Gambacorti-Passerini-553-61.pdf

Accesso chiuso

Tipologia: Pdf editoriale (Version of record)
Licenza: Tutti i diritti riservati
Dimensione 323.54 kB
Formato Adobe PDF
323.54 kB Adobe PDF   Richiedi una copia

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/600832
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 345
  • ???jsp.display-item.citation.isi??? 310
social impact