Treatment Outcomes in Patients Treated with Tyrosine Kinase Inhibitors in "Slovak Registry of Chronic Myeloid Leukemia" (CAMELIA SK)

Introduction: With the onset of tyrosine kinase inhibitors (TKI) to treat patients with CML, the number of patients and overall survival increased and quality of life significantly improved. The basic principle of therapy was also changed, according to the clinical practice now it is aimed at early induction of deep molecular response.

Objective: To characterize the CML patient population and TKI treatment results in clinical practice in CML patients in Slovak republic (SR).

Methods: The observational study "Slovak registry of chronic myeloid leukemia" (CAMELIA SK) was launched in 2005 by Novartis. Patients with Ph+ CML were enrolled into study after signing the informed consent. Thus the study has a retrospective part (131 patients) and prospective group of 586 CML patients. By June 2016, the Registry contained information about 717 patients from 7 centers of SR. The annual increase of newly diagnosed CML cases ranged from 2 to 56 people per year (median 35.5). Characteristics of patients in the Registry: in June 2016, 489 (68.2%) were alive, 181 (25.2%) dead and 47 (6.6%) lost to follow-up. Median follow-up in alive patients was 79 months (1 to 324 months). Median age at CML diagnosis was 50 years (range 15 - 86 years); male 52.7%. Chronic phase (CP) was in 664 (92.6%), accelerated phase in 37 (5.2%) and blast crisis in 16 (2.2%) patients. Sokal risk group's ratio was 35.8%/34.3%/25.7%/4.2% for low, intermediate, high risk and unknown, respectively. Hasford risk group's ratio was 41.6%/40.6%/13.4%/4.5% for low, intermediate, high risk and unknown, respectively, and EUTOS risk group's ratio was 83.8%/11.7%/4.5% for low, high risk and unknown, respectively.

Results: The data for this analysis were available for 594 patients (82.8% of patients in the Registry) treated by tyrosinkinase inhibitors (TKI). First line TKI treatment was initiated in 467 patients: 363 (77.7%) started imatinib (IM), 101 (21.6%) nilotinib (NIL) and 3 (0.7%) dasatinib (DAS). Higher line TKI treatment was initiated in 127 patients, mostly after interferon-alpha or allogeneic stem cell transplantation (SCT), 125 (98.4%) of them started IM and 2 (1.6%) NIL. Time from diagnosis until first line TKI treatment was 0-112.7 months (median 1.1). One TKI drug was used in 388 (65.3%) patients, 2 drugs in 146 (24.6%), 3 drugs in 57 (9.6%) and 4 drugs in 3 (0.5%) patients.

From these 594 patients, 448 (75.4%) are alive, 28 (4.7%) are lost to follow-up and 118 (19.9%) died, mostly because of other diseases - 50%; 30.5% died because of CML, 17.8% because of disease progression and 1.7% by SCT.

From 363 patients who started first line IM (93.7% in CP), optimal treatment response from evaluable patients according to ELN2013 achieved 57.8%, 49.2%, 17.3%, 27.9% and 36.5% after 3, 6, 12, 24 and 48 months, respectively. Median length of treatment was 39.6 months (0.2-149.1). Change of treatment to 2^ndline was performed in 155 (42.7%) patients. In total, 264 (72.7%) patients are still on TKI treatment, 3 (0.8%) progressed to advanced phase, 5 (1.4%) underwent SCT and 42 (11.6%) patients are lost to follow up, had adverse events (AE) or discontinued treatment from other reasons. The death occurred in 49 (13.5%) patients.

From 101 patients who started first line NIL (98% in CP), optimal treatment response from evaluable patients according to ELN2013 achieved 82.4%, 82.6%, 59.3%, 66.6% and 83.3% after 3, 6, 12, 24 and 48 months, respectively. Median length of treatment was 18.4 months (0.2-97). Change of treatment to 2^ndline was performed in 11 (10.9%) patients. In total, 87 (86.4%) patients are still on TKI treatment, nobody progressed to advanced phase and 10 (9.7%) patients are lost to follow up, had AE or discontinued treatment from other reasons. The death occurred in 4 (3.9%) patients.

53 patients in accelerated or blastic phase started mostly IM treatment (18, 34%), combined chemotherapy (12, 22.6%) or interferon-alpha (9, 17%). 4 patients underwent SCT, 2 started NIL, 2 DAS and 6 another treatment. In total, 35.8% patients are alive, 52.8% died and 11.3% are lost to follow up.

Conclusions: The observational study "CAMELIA SK" is the largest registry of hematological diseases in Slovakia, providing information about CML patients receiving TKI therapy more than 10 years. We approved the efficacy and safety of second generation TKI nilotinib in newly diagnosed CML patients as first line therapy. More patients achieved optimal response in short period than on imatinib.