Chlorambucil PLUS Rituximab As FRONT-LINE THERAPY in Elderly or Unfit Patients Affected by B-CELL Chronic Lymphocytic Leukemia: Results of A Single-Centre Retrospective Analysis

Abstract 4604

Currently standard first line therapy for fit patients with B-CLL/SLL are fludarabine-based regimens. Elderly patients or patients with comorbidities poorly tolerate purine analogue-based chemotherapy and they are often treated with Chlorambucil (Chl). However, complete response (CR) and overall response (OR) rates with Chl are relatively low.

We now investigated whether the addition of Rituximab to Chl will improve the efficacy without impairing the tolerability in elderly and unfit patients. We included in our study 23 elderly or unfit patients that had not received prior therapy. All patients were treated with Chl (1mg/Kg monthly for 8 cycles) plus Rituximab (375 mg/m² for the first course and 500 mg/m² for subsequent cycles until the 6^th cycle).

Fifteen patients were male and 8 were female, with a median age at the time of treatment of 70 years (range 58 to 81 years). Eight patients (35%) were unfit with a median age of 68 years (range 58 to 79 years). Five patients were in stage A/I, 10 were in stage B/II and 8 in stage C/IV. FISH analysis was done in all patients: 78% showed karyotype abnormalities. Low-risk FISH karyotype was detected in 20/23 pts: 12 of them had del(13q14), 1 had trisomy 12, 1 trisomy 12 and del(13q14) and 6 had a normal karyotype. Three patients showed a high risk karyotype: all of them had del(11q). None of the patients had a 17p deletion. Nineteen pts were studied for IGHV mutational status (83%), 12 had unmutated while 7 had mutated IGHV genes.

Twenty-one patients were evaluable for response to treatment. The median number of Chl and RTX cycles administered in the 21 patients who completed the treatment protocol was 8 (range 6 to 8 cycles) and 6 (range 4 to 6 cycles) respectively. The median total dose of Chl administered during the treatment was 600 mg per patient (median dose 85 mg each cycle). The median dose of RTX administered was 4000 mg per patient (median dose 710 mg each cycle). Among 21 pts evaluable for response, the Overall Response Rate (ORR) was 76%. Six pts (28%) obtained a complete response, 10 pts (48%) obtained a partial response. No significant statistical differences were noticed in terms of ORR for age more or less than 70 years, fitness status, bulky disease, cytogenetic risk abnormalities or IgVH, ZAP-70 and CD38 categories. On an intention to treat basis the median PFS was not reached at a median time of 21 months (range 2–45). Eleven pts experienced progression after treatment at a median time of 20 months (range 2–36). No significant statistical differences were found among the analyzed risk groups.

After a median time of 25 months (range, 2–45 months), TTR was not reached. No significant statistical differences were noticed between the Unmutated and Mutated IgVH groups and for ZAP-70 and CD38 categories with respect to TTR. At present the median follow-up is 29 months, with an OS rate of 80% (19/23). None of the risk factors analyzed were found to influence significantly the OS.

In conclusion, this study suggests that the combination Chl-R is a safe and effective therapeutic option for untreated B-CLL pts that are not eligible for fludarabine treatment because of age and/or comorbidities. A multicentre trial to confirm these data is planned.