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Randomized Controlled Trial
. 2016 Jun;30(6):1255-62.
doi: 10.1038/leu.2016.20. Epub 2016 Feb 9.

Secondary malignancies in chronic myeloid leukemia patients after imatinib-based treatment: long-term observation in CML Study IV

M B Miranda  1 , M Lauseker  2 , M-P Kraus  1 , U Proetel  1 , B Hanfstein  1 , A Fabarius  1 , G M Baerlocher  3 , D Heim  4 , D K Hossfeld  5 , H-J Kolb  6 , S W Krause  7 , C Nerl  8 , T H Brümmendorf  9 , W Verbeek  10 , A A Fauser  11 , O Prümmer  12 , K Neben  13 , U Hess  14 , R Mahlberg  15 , C Plöger  16 , M Flasshove  17 , B Rendenbach  18 , W-K Hofmann  1 , M C Müller  1 , M Pfirrmann  2 , A Hochhaus  19 , J Hasford  2 , R Hehlmann  1 , S Saußele  1
Affiliations
Randomized Controlled Trial

Secondary malignancies in chronic myeloid leukemia patients after imatinib-based treatment: long-term observation in CML Study IV

M B Miranda et al. Leukemia. 2016 Jun.

Abstract

Treatment of chronic myeloid leukemia (CML) has been profoundly improved by the introduction of tyrosine kinase inhibitors (TKIs). Long-term survival with imatinib is excellent with a 8-year survival rate of ∼88%. Long-term toxicity of TKI treatment, especially carcinogenicity, has become a concern. We analyzed data of the CML study IV for the development of secondary malignancies. In total, 67 secondary malignancies were found in 64 of 1525 CML patients in chronic phase treated with TKI (n=61) and interferon-α only (n=3). The most common malignancies (n⩾4) were prostate, colorectal and lung cancer, non-Hodgkin's lymphoma (NHL), malignant melanoma, non-melanoma skin tumors and breast cancer. The standardized incidence ratio (SIR) for all malignancies excluding non-melanoma skin tumors was 0.88 (95% confidence interval (0.63-1.20)) for men and 1.06 (95% CI 0.69-1.55) for women. SIRs were between 0.49 (95% CI 0.13-1.34) for colorectal cancer in men and 4.29 (95% CI 1.09-11.66) for NHL in women. The SIR for NHL was significantly increased for men and women. An increase in the incidence of secondary malignancies could not be ascertained. The increased SIR for NHL has to be considered and long-term follow-up of CML patients is warranted, as the rate of secondary malignancies may increase over time.

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Conflict of interest statement

BH has received honoraria from Bristol-Myers Squibb (BMS) and research funding from Novartis; SWK honoraria and research funding by Novartis; MCM honoraria and research funding from Novartis, BMS, ARIAD and Pfizer; MP honoraria from BMS and consultancy from Novartis; AH honoraria from Novartis, BMS, ARIAD, consultancy from Novartis and research funding from Novartis, ARIAD and Pfizer; RH research funding from Novartis and BMS and SS honoraria from Novartis, BMS, Pfizer, ARIAD and research funding from Novartis and BMS. The other authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Consort statement of the CML study IV and occurrence of secondary malignancies per recruitment arm.
Figure 2
Figure 2
Probability of survival with or without the appearance of secondary malignancies. (a) Overall survival from time of diagnosis of CML. (b) Progression-free survival from time of diagnosis of secondary malignancy.
Figure 3
Figure 3
Cumulative incidence of all secondary malignancies according to age ⩽50 vs >50 years.
Figure 4
Figure 4
SIRs of secondary malignancies within CML study IV for men and women compared with normal population for different tumor types. (a): SIRs of men (b) and SIRs of women.
See this image and copyright information in PMC

References

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