Response To 1^st-Line Treatment With BR Or FCR In Patients With Chronic Lymphocytic Leukaemia: First Outcome Data From The German Prospective TLN Registry

Fludarabine, cyclophosphamide, rituximab (FCR) is currently considered the standard of care for medically fit patients (pts) with untreated chronic lymphocytic leukaemia (CLL). However, due to its significant haematological toxicity other, potentially less toxic regimens are currently under investigation. Results of the phase III trial CLL 10 of the German CLL-Study Group (GCLLSG) comparing FCR to bendamustine, rituximab (BR) are eagerly awaited. Since clinical trials are restricted to highly selected pts, we here investigated effectiveness of BR and FCR in unselected pts with CLL treated in routine practice by German office-based haematologists.

The open, longitudinal, multicentre, clinical registry on lymphoid neoplasms (TLN Registry, ClinicalTrial.gov registry NCT00889798) prospectively collects data on the treatment of pts with lymphoid B-cell neoplasms as administered by a network of German office-based haematologists. Pts are followed for 5 years. A broad set of data regarding patient and tumour characteristics, comorbidities, all systemic treatments and response rates, progression-free survival and overall survival are recorded. Automated plausibility and completeness checks with subsequently generated queries by the electronic data capture system ensure data reliability. In addition, data managers regularly check for plausibility and issue queries. Since May 2009, 111 sites have actively recruited a total of 2897 pts.

381 pts with CLL, recruited at the onset of their 1^st-line therapy and treated with BR (69%) or FCR (31%), were included in this analysis. The choice of the regimen was upon the decision of the treating physician in accordance with the patient´s informed consent.

Pts are median 70 years (yrs) old (range 21-90 yrs), 68% male, 42% have Binet stage C, 27% present with B symptoms, 13% with bulky disease and 66% with at least one comorbidity.

Clinical and tumour characteristics differ between pts receiving BR or FCR: Pts treated with BR are older (median 71 vs. 65 yrs; p<0.0001) and present more often with Binet C (45% vs. 35%) or comorbidities (67% vs. 62%).

Objective response rate (ORR) was assessed by the local site: 93% of pts receiving BR and 95% receiving FCR responded to 1^st-line therapy; the clinical complete remission rate (CR) was reported to be 49% after BR and 39% after FCR, respectively. Both regimens were applied with median 6 cycles.

In univariate analyses none of the parameters tested (type of 1^st-line regimen, age, sex, B symptoms, bulky disease, tumour stage, comorbidities) had a significant impact on the response rate. Also, in a multivariate logistic regression model adjusted for the type of regimen (BR vs. FCR) and age neither factor had a significant impact on the response rate. At this point the small number of non-responders (n=17) precluded calculation of models adjusted for more than two parameters.

After a median observation time of 17 months (maximum 40 mth), 93% of pts receiving BR are alive and 8% have received 2^nd-line therapy. In pts receiving FCR 96% are alive and 6% have received 2^nd-line therapy. Overall 5% of pts are lost to follow-up.

Our data show that previously untreated pts with CLL receiving BR or FCR in routine practice differ, with BR preferentially given to older pts with comorbidities. Nevertheless, response rates to 1^st-line treatment with BR or FCR are comparable, even after statistical adjustment for age at the start of therapy. If the CLL10 trial confirms these results, BR could present an alternative 1^st-line treatment to medically fit pts with CLL.

BR: bendamustine + rituximab ± prednisone │ FCR: fludarabine + cyclophosphamide + rituximab ± prednisone

Knauf:Mundipharma, Janssen, Roche Pharma: Consultancy, Honoraria.