12th Congress of the European Hematology ... - Haematologica

12 th Congress of the European Hematology Association
0657
ASSESSING THE LONGTERM EFFECT OF IMATINIB MESYLATE IN BONE METABOLISM OF
PATIENTS WITH CHRONIC MYELOID LEUKEMIA
C. Kartsios, M. Christopoulou, A. Lazaridou, E. Verrou, M. Koltsida,
A. Banti, C. Chatziangelidou, E. Katodritou, K. Zervas
Theagenion Cancer Hospital, THESSALONIKI, Greece
Background and Aims. Imatinib mesylate (IM) inhibits several tyrosine
kinases, including BCR-ABL, the C-KIT receptor, and the platelet-derived
growth factor receptors α and β, all of which are associated with disease.
Recently, IM has been shown to alter bone metabolism by inhibiting
osteoclast differentiation and function in in vitro models. In the present
study, bone metabolism markers were determined in a cohort of chronic
myeloid leukaemia (CML) patients who were extensively treated with
IM. Patients and Methods. Seventeen CML patients [M/F: 11/6, median
age: 62(48-74) years, median time on IM: 48(10-56) months, median daily
dose of IM: 400(400-800) mg] and 10 healthy volunteers [M/F: 7/3,
median age: 57(38-64) years] were studied. All CML patients were in
chronic phase when IM was started. At the time of study, 13/17 patients
were in complete cytogenetic response (cR), one patient was in partial
cR and 3 patients were in hematological remission. We measured the
plasma levels of intact parathyroid hormone (PTH) and the serum levels
of total calcium (Ca) and phosphate (P). Evaluation of the bone formation
was made by measuring total alkaline phosphatase (ALP), procollagen
type I N-terminal propeptide (PINP) and osteocalcin (OSC).
Bone resorption was assessed by determination of the plasma C-telopeptide
of collagen cross-links (CTX). None of the patients had metabolic
bone disease, and none was receiving medications known to influence
the metabolism of calcium. Results. Hypocalcemia (total Ca 5% of patients are reported
in the table. Grade 3/4 hematologic AEs for dasatinib were 2-3 times
greater compared to those for nilotinib. Biochemistry abnormalities
occurring in > 5% of nilotinib patients included lipase increase in 16.8%,
elevated bilirubin in 10.3%, and hypophosphatemia in 9.7%; dasatinib
patients experienced hypophosphatemia in 13% and hypocalcemia in
246 | haematologica/the hematology journal | 2007; 92(s1)
9%. Grade 3/4 non-hematologic AEs such as pleural/pericardial effusions
were also higher for dasatinib than nilotinib. Summary and conclusions.
The toxicity profiles of the second generation TKIs for imatinib
resistant/intolerant CML-AP are different. Nilotinib’s lower rates of
Grade 3/4 hematologic AEs and GI hemorrhage may result in reduced
resource utilization. Further research is warranted to assess the economic
impact of the differences in safety profiles.
Table 1. Grade 3/4 AE rates: nilotinib v. dasatinib.
0659
IMATINIB EFFICACY AND TOLERABILITY IN ADVANCED AGE (>70 YEARS) CML PATIENTS
V. Giai, 1 D. Ferrero, 2 M. Genuardi, 2 M. Strugli, 2 P. Pregno, 3
G. Rege-Cambrin, 4 A. Darbesio, 5 C. Boccomini, 6 M. Pini, 7
M. Boccadoro1 1 Azienda Ospedaliera San Giovanni Battist, TORINO; 2 Div. di Ematologia
Universitaria, TORINO; 3 Azienda Ospedaliera S. Giovanni Battista, TORI-
NO; 4 Azienda Ospedaliera San Luigi Gonzaga, ORBASSANO, TORINO;
5 Azienda Ospedaliera di Chivasso, CHIVASSO, TORINO; 6 Azienda
Ospedaliera Cardinal Massaia, ASTI; 7 Azienda Ospedaliera SS Antonio e
Biagio, ALESSANDRIA, Italy
In the last years, CML prognosis had improved after introduction of
tyrosine-kinase inhibitor imatinib-mesylate, that induces a complete
cytogenetic response in about 80% of patients when used as a front-line
therapy in chronic phase (O'Brien SG et al. N Engl J Med. 2003;348: 994-
1004) However, the optimal CML treatment in advanced age has not
been definitely established. Before imatinib advent, old CML patients
were handled just with palliative chemotherapy because of the impossibility
for such patients to tolerate bone marrow transplantation or α
interferon. Moreover, age is a prognostic negative factor for survival in
CML (Sokal JE et al.: Blood 1984; 63: 789-99); therefore, most of old
CML patients likely died of blastic phase CML. Imatinib has opened
new therapy opportunities for advanced age patients. However, in spite
of a median age for CML patients around 60, most of Imatinib studies
mainly involved patients below that age. Two papers actually reported
similar tolerance and efficacy of imatinib below and above the age of 60
(Cortes J et al.: Cancer. 2003; 98:1105-13; Latagliata R et al.: Leuk Res.
2005; 29:287-91) but no information has been provided about older
patients, above the age of 70. Indeed, median age was 66 in one of the
two papers and not reported in the other. Therefore, some doubts still
exist about imatinib tolerability and cost effectiveness in old patients. In
this study, we evaluate Imatinib tolerance and efficacy in 37 CML
patients at or above the age of 70 (median age at the beginning of imatinib
treatment was 76, range 70-87). One patient was treated in blastic
phase, four in accelerated, one in second chronic and 31 in first chronic
phase. Sokal score of first chronic phase patients was: low risk in 6
patients, intermediate in 18 and and high risk in 6. Seventeen chronic
phase patients received imatinib as a front-line treatment, the other had
received different previous therapies. The great majority presented with
associated comorbidities. Grade 3-4 fluid retention was significantly
more frequent (13%) than previously reported for younger patients.
Conversely, the frequency of other hematological (neutropenia and
thrombocytopenia) and extra-hematological toxic effects (cutaneous