here's the paper:
[154] Second Malignancies Following Treatment of Chronic Myeloid Leukemia in the Tyrosine Kinase
Inhibitor Era. Själander. Background: Since continuous treatment with tyrosine kinase inhibitors (TKIs) has
dramatically improved the survival of patients with chronic myeloid leukemia (CML), it is of interest to examine
the possible risk of long-term adverse events. Previous studies have presented conflicting results regarding
risk of second malignancies. Our aim was to examine the development of second malignancies (except acute
myeloid or lymphoblastic leukemia, myelodysplastic syndromes or non-melanoma skin cancer) in CML
chronic phase patients diagnosed after the introduction of TKI treatment. Materials and methods: We
studied the development of second malignancies in 868 patients diagnosed with CML in chronic phase 2002
to 2011 using the Swedish CML register, cross-linked to the Swedish Cancer register. Each patient was
followed from the time of CML diagnosis until death from any cause, date of allogeneic hematopoietic stem
cell transplantation (SCT) or end of study on December 31, 2011, whichever came first. SCT was used as an
endpoint because of the well established increased risk of second malignancies after this procedure.
Standardized Incidence Ratios (SIR) were calculated to assess the risk of a second malignancy by dividing
the number of observed second malignancies with the number of expected malignancies in the Swedish
population, using data from the Swedish Cancer Register. The expected numbers of malignancies were
determined by dividing the CML population according to 5-year age groups, sex, region of residence (6
regions) and calendar year. The number of person-years in each stratum was multiplied with the incidence of
malignancies or deaths found in the corresponding strata in the general population. Results: With a median
follow-up of 3.7 (range 0-9.9) years, 65 (7.5%) patients developed 75 second cancers (non-hematologic), 49
of these of invasive type. Compared to expected rates in the background population matched by age, sex,
region of residence (6 regions) and calendar year, the risk of second malignancies was significantly higher in
the CML cohort, with a Standardized Incidence Ratio (SIR) of 1.5 (95 % CI 1.13-1.99). SIR before and after
the second year following diagnosis of CML was 1.6 (95 % CI 1.004-2.38) and 1.5 (95 % CI 0.98-2.11),
respectively. Looking at CML subpopulations, the increased risk of developing a second malignancy reached
statistical significance for females (SIR: 1.8; 95 % CI 1.18-1.99), but not for males (SIR: 1.3; 95 % CI 0.85-
1.91), and for patients above 60 years of age at diagnosis (SIR: 1.5; 95 % CI 1.05-1.96). Assessment of risk
by cancer type was hampered by small numbers. However, the data at hand indicate an increased risk for
gastrointestinal cancer (SIR: 3.0; 95 % CI 1.60-5.16), as well as nose and throat cancer (SIR: 37.1; 95 % CI
7.46-108.40), table 1. Conclusions: Utilizing large, population-based registries with data accumulated during
the TKI era, our results indicate that CML patients, compared to the normal control population, are at an 50%
increased risk of developing a second malignancy. Similar SIR before and after the second year following the
diagnosis of CML may indicate that these findings are linked to the CML disease itself, rather than to the TKI
treatment. Further studies and longer follow-up seem however warranted. Physicians caring for CML patients
should be aware of signs and symptoms of other malignancies in this patient population.
Table 1. Standardized Incidence Ratios for second malignancies (excluding cases of non-melanoma skin
cancer, AML, ALL and MDS) among 868 Swedish CML patients diagnosed between 2002 and 2011. Total
follow up time 3293 person-years (median 3.7 years).
Variable Observed Expected SIR (Observed/Expected) 95 % CI for SIR
Overall 52 34 1.5 1.13-1.99
Men 26 20 1.3 0.85-1.91
Women 26 14 1.8 1.18-2.66
Age <60 years 10 5 1.9 0.89-3.42
Age ³ 60 years 42 28 1.5 1.05-1.96
Second cancer type
Prostate 14 8 1.8 0.96-2.94
Gastrointestinal 13 4 3.0 1.60-5.16
Gynecological 4 1 3.6 0.98-9.30ASH 2014 CML report Page 8 of 29 9th December 2014
Nose and Throat 3 0,1 37.1 7.46-108.40
Lung 2 2,7 0.7 0.08-2.67
Breast 4 4,2 0.98 0.26-2.45