Cladribine with or without prednisone in the treatment of previously treated and untreated B‐cell chronic lymphocytic leukaemia — updated results of the multicentre study of 378 patients

Abstract

Between January 1992 and January 1999, we treated 378 B-chronic lymphocytic leukaemia (CLL) patients with cladribine (2-CdA), and 255 of the patients were also treated with prednisone. A total of 194 patients were previously untreated, and 184 had relapsed or refractory disease after previous other therapy. Complete response (CR) was obtained in 111 (29.4%) and partial response (PR) in 138 (36.5%) patients, giving an overall response (OR) rate of 65.9%. CR and OR were achieved more frequently in patients in whom 2-CdA was a first-line treatment (45.4% and 82.5% respectively) than in the pretreated group (12.5% and 48.4% respectively) (P < 0.0001). The median duration of OR for previously untreated patients was 14.7 months and for pretreated patients 13.5 months (P = 0.09). The median survival evaluated from the beginning of 2-CdA treatment was shorter in the pretreated group (16.3 months) than in the untreated group (19.4 months) (P < 0.0001). A total of 117 (63.9%) patients died in the pretreated group and 63 (32.6%) in the untreated group. In pretreated patients, 2-CdA + prednisone (P) and 2-CdA alone resulted in similar OR (51.0% and 45.0% respectively; P = 0.4). In contrast, in untreated patients, 2-CdA + P produced a higher OR (85.4%) than 2-CdA alone (72.1%) (P = 0.04). Infections and fever of unknown origin, observed in 91 (49.4%) pretreated and 74 (38.1%) untreated patients (P = 0.03), were the most frequent toxic effects. Our results indicate that 2-CdA is an effective, relatively well-tolerated drug, especially in previously untreated CLL.

Cladribine combined with cyclophosphamide and mitoxantrone as front-line therapy in chronic lymphocytic leukemia

“…It should be emphasised, that in spite of the large proportion of patients who have responded to treatment, the response rate does not seem greater than in our earlier studies with 2-CdA in monotherapy or combined with prednisone. 7,8 It is of interest that the shortened administration time from 5 (CMC5) to 3 (CMC3) days has not resulted in a lower CR rate (30% and 28.6%, respectively) or overall response rate (55% and 69%, respectively). Similarly, we observed earlier the lack of influence of a shorter administration time of 2-CdA within a CMC programme on the outcome in pretreated indolent lymphoma.…”

“…7,[19][20][21] In the first part of the study, CMC protocol consisted of 2-CdA administered at a dose 0.12 mg/kg in 2-h i.v. infusion for 5 (CMC5) days, mitoxantrone 10 mg/m 2 i.v.…”

“…It is mainly used in the treatment of hairy cell leukemia, but it is also highly active in chronic lymphocytic leukemia (CLL), with an overall response rate (OR) and complete remission rate (CR) comparable to that achieved with FAMP. [4][5][6][7] There are some opinions that 2-CdA is associated with more frequent and problematic myelosuppression. However, direct comparison of both agents in the randomized study of CLL patients has not been published as of this time.…”

Alkylating agents and nucleoside analogues in the treatment of B cell chronic lymphocytic leukemia

“…In our group of 184 patients with a relapse or refractory disease following prior therapy with chlorambucil and prednisone, some of them also with COP and/or CHOP, 2-CdA induced clinical CR in 12.5% and overall response (OR) in 48.4%. 14 Chlorambucil is less active as a second line treatment in patients refractory to NA. In patients primarily resistant to 2-CdA, the OR rate after treatment with chlorambucil and prednisone as an alternative regimen was only 33%.…”

“…[7][8][9][10] More recently, renewed interest in CLL therapy has been created by the introduction of novel nucleoside analogues (NA), particularly fludarabine (FAMP) and cladribine (2-chlorodeoxyadenosine, 2-CdA), as well as combined chemotherapy. [11][12][13][14][15][16][17][18] The place of alkylating agents and NA in the management of CLL patients at the beginning of the new millennium, based on the results of randomized clinical trials, is the subject of this review.…”