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Real-world results of first-line therapy in CLL
this analysis showed a prognostic impact of IGHV status both on OS (P<0.01) and PFS (P=0.02) (data not shown).
In univariate analysis, PFS and OS were also associated with type of hospital (P=0.05 and P=0.04) (Figure 2C), adherence to treatment guidelines (P=0.001 and P=0.006), and Rai stage (P=0.042 and P=0.005). Median PFS and OS at university/regional hospitals versus other hospitals were 28 versus 22 months and 61 versus 54 months, respectively. Those treated according to national guide- lines showed a median PFS and OS of 26 months and 58 months, respectively. The correlating time for those treat- ed outside trials or guidelines were 13 months and 44 months, respectively and for those in clinical trials 19 months and 66 months, respectively. Patients on medica- tion with ASA or statins also showed a significantly shorter PFS and OS (P<0.001 and P=0.007) (by univariate analysis only).
Safety
Infections of grade III or higher were significantly asso- ciated with type of treatment, affecting 19% of the CLB- treated patients and 30% in the FCR group (P=0.006) (Table 2). Richter transformation occurred in 5.5% of the patients, was significantly associated with del(17p) (P=0.04), and was equally distributed between types of first-line therapy. The median time to transformation was three years from diagnosis and 1.5 years from first-line treatment. Secondary malignancies affected 15% of the patients and were equally distributed between types of first-line therapy. About one-third of the secondary
malignancies consisted of basal cell carcinomas. MDS/AML affected only 1% of the patients and the other secondary malignancies were solid tumors.
Discussion
Randomized controlled trials (RCTs) remain the scien- tific ideal for evaluation of novel treatments. However, in studies on malignancies, RCTs are sometimes not suffi- cient to address the evidentiary requirements of regulat- ing authorities30 and payers as patients are selected on strict inclusion/exclusion criteria and sufficient data on overall survival and long-term follow up is often not pro- vided.31 In addition, the comparative arm in clinical trials may be chosen to favor the treatment of investigation. Therefore, regulating authorities increasingly look for real-world data for additional comparison when evaluat- ing new cost-intensive drug regimens. However, reliable data on consecutive patients in routine health-care may be difficult to obtain.
This is the largest retrospective cohort of strictly con- secutive real-world patients from a well defined geo- graphical region (Sweden) with a comparatively long complete follow up. By using high-quality Swedish data bases (National Cancer Registry/Swedish CLL-registry) including all patients diagnosed in Sweden within a spec- ified time period, followed by in-depth analysis of each individual medical file, we were able to obtain a complete record of all patients diagnosed with and receiving first-
AB
CD
Figure 2. Overall survival (OS) after first-line therapy. OS according to (A) treatment, (B) fluorescence in situ hybridization cytogenetic status, (C) type of hospital, and (D) age. F/FC: fludarabine/fludarabine in combina- tion with cyclophosphamide; CLB+/- R: chlorambucil and rituximab; FCR: fludarabine in combination with cyclophosphamide and rituximab; B/BR: bendamustine/bendamustin and rituximab; ALEM: alemtuzumab; CHOP/CVP+/-R: cyclophosphamide +hydroxydaunorubicin+vincristine+p rednisone/cyclophosphamid+vin- cristine+prednisone+rituximab.
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