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Real-world results of first-line therapy in CLL
sufficient power for this time period (only a small fraction of patients was tested); this was, therefore, excluded from the mul- tivariate analysis. However, regarding IGHV, the prognostic impact of the whole population was analyzed separately. Patients who had received allogeneic stem cell transplant after first-line therapy (n=2) were excluded from PFS and OS analysis.
Results
In total, 3672 patients diagnosed with CLL between 2007 and 2013 were identified from the Swedish Cancer registry for whom all (100%) medical files were available for review. Out of these, 1053 patients had started first- line treatment between 2007 and 2013, thus being subject to further in-depth analysis. The six geographical regions included 10-23% of the patients each. Sparsely populated areas included fewer patients (10%) than those with the larger cities. Median follow up for all patients was 4.8 years.
Baseline patients’ characteristics
Baseline characteristics at start of first-line treatment are shown in Table 1. Median age at first-line treatment was 71 years (range 31-96 years). Thirty-four percent were females and the majority (53%) had advanced dis- ease with Rai stages III-IV. Patients were generally in a good performance status with 97% in Eastern Co-opera- tive Oncology Group (ECOG) grade 0-2. In total, results of cytogenetic assessment were available for 599 patients (57%); more results were available in the latter time peri- od (64% 2010-2013 vs. 47% 2007-2009). Since 2010, when FISH was generally recommended in the national guidelines, there has been a significant difference in the frequency of cytogenetic analysis between the regions (50.8-72.5%; P=0.003) and cytogenetic analysis has been more often performed at university hospitals (80%) than other types of hospitals (55-60%) (P<0.001). The older the patient, the more rarely was the analysis performed. In the younger patient group [<65 years (y)], cytogenetic analysis was available in 87% compared to 75% and 39% in the middle aged (65-74 y) and oldest (≥75 y) groups, respectively. The frequency of del(17p) was 4% and 11% in the earlier and later time periods, respectively, out of all patients tested (n=599).
Analysis of IGHV mutational status was, and is still, optional according to the Swedish guidelines and thus was analyzed only in a minority of patients (n=224; 20%): 12% were unmutated and 8% mutated.
Treatment
The majority (68%) of patients started first-line treat- ment in the later time period (2010-2013). Most patients (63%) were treated at County/Rural hospitals (i.e. neither university nor regional hospitals), whereas 32% received their treatment at university hospitals. In almost all cases, the treatment decision was taken at the same institution as that in which the patient was subsequently treated. First-line treatments are shown in Table 2. Type of treat- ment was unknown in 4 patients and in 4 could not be evaluated. The most frequently used regimens were: chlorambucil (CLB/CLB-R) (39%), FCR (27%) and FC (16%). Nearly all patients (95%) receiving CLB did not receive rituximab. Only 6% of the patients received ben- damustin (B) or (BR) and almost all were treated in the
later study period. For all regimens, dosing intensity was similar across geographical regions and type of institu- tion. Treatment was given according to the national guidelines in 80% (n=843) of the patients, 5% (n=49) were included in clinical trials, and in 15% (n=153) the treatment was individual, i.e. neither according to guide- lines nor to a clinical protocol. The median age was high- er for patients receiving chlorambucil (79 y) and younger for patients receiving FCR (64 y) compared to other chemotherapy-based regimens (F/FC 68 y, B/BR 72 y, CHOP/CVP +/- R 71 y). The median age in the CLB group did not change over the study period. In patients aged 75 y or over, 73% received CLB, F/FC (9%) and B/BR (5%), whereas in patients under 65 years of age, the most com- monly used treatment was FCR (53%) followed by F/FC (22%). Those who received CLB also generally had a worse performance status, with 20% in ECOG 2-3 com- pared to 4% and 5% of those receiving FCR and BR, respectively. Notably, university hospitals used CLB sig- nificantly (P=0.01) less often (30%) than other types of
Table 1. Baseline characteristics at start of first-line therapy (n=1053).
Factor
Age, median [range]
Male
ECOG performance status
0-1
2
3 Missing
Binet stage
A-B
C Missing
Rai stage 0-II
III-IV
Missing
FISH
del(13q) Normal Trisomy 12 del(11q) del(17p) Missing
Hospital type University Regional County/Rural Missing
Treatment
Guidelines Clinical trial Individual Unknown
N (%)
71 years [31-96]
691 (66)
916 (87) 102 (10) 19 (2) 16 (2)
520 (49) 499 (47) 34 (3)
474 (45) 556 (53) 23 (2)
198 (19) 112 (11) 103 (10) 94 (9) 92 (9) 454 (43)
341 (32) 51 (5) 660 (63) 1 (0)
843 (80) 49 (5) 153 (15) 8 (1)
n/N: number; ECOG: Eastern Co-operative Oncology Group; FISH: fluorescence in situ hybridization.
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