Cladribine (2-CDA) given as subcutaneous bolus injections is active in pretreated Waldenstrom's macroglobulinaemia

Summary. Clinical trials with intravenous cladribine infu- sions in pretreated patients with Waldenstrom's macro- globulinaemia have shown a response rate of 40%. Our pharmacokinetic studies revealed that the bioavailability of subcutaneous cladribine is complete but that the concentra- tion-time profile is very different from intravenous admin- istration. We designed this phase II multi-institutional trial to study the activity and toxicity of cladribine given as s.c. bolus injections in patients with symptomatic Walden- strom's macroglobulinaemia. Between May 1993 and October 1995, 25 patients were accrued: male/female 18/7, median age 65 years (range 44- 85). All except one patient had been pretreated with more than one regimen (median 2, range 0-10). 18 patients had progressed under previous therapy and six were in relapse. All patients received cladribine for a total dose of 0 . 5 mg/kg per cycle as s.c. bolus injections divided over 5 d at > 4 week intervals, for a maximum of six cycles. All 25 patients were evaluable for toxicity and response. A total of 67 cycles were administered (median 3 cycles, range 1-6). Overall response rate including disease stabilization which had been progressive under previous therapy was 68%. 10 patients (40%, 95% CI 21-61%) achieved a partial remission. Seven responders had been progressive under previous therapy. Maximum responses were reached no later than the third cycle. Median time to treatment failure and remission duration were 4.4 (range 0.5-33) and 8 months (5-29), respectively. Four patients (16%) suffered from infections W.H.O. grade > 2 (pneumonia grade 2, Staphylo- coccus septicaemia grade 3, viral encephalitis and pneumo- nia, both grade 4 with complete resolution). No other severe adverse events were observed. Cladribine given as s.c. 5 d bolus injections was found to be active in pretreated Waldenstrom's macroglobulinaemia and resulted in durable remissions.