CLADRIBINE (2-CDA) GIVEN AS SUBCUTANEOUS BOLUS INJECTIONS IS ACTIVE IN PRETREATED WALDENSTROMS MACROGLOBULINEMIA

Clinical trials with intravenous cladribine infusions in pretreated pa tients with Waldenstrom's macroglobulinaemia have shown a response rat e of 40%. Our pharmacokinetic studies revealed that the bioavailabilit y of subcutaneous cladribine is complete but that the concentration-ti me profile is very different from intravenous administration, We desig ned this phase II multi-institutional trial to study the activity and toxicity of cladribine given as s.c. bolus injections in patients with symptomatic Waldenstrom's macroglobulinaemia. Between May 1993 and Oc tober 1995, 25 patients were accrued: male/female 18/7, median age 65 years (range 44-85). All except one patient had been pretreated with m ore than one regimen (median 2, range 0-10), 18 patients had progresse d under previous therapy and six were in relapse. All patients receive d cladribine for a total dose of 0.5 mg/kg per cycle as s.c. bolus inj ections divided over 5 d at greater than or equal to 4 week intervals, for a maximum of six cycles. All 25 patients were evaluable for toxic ity and response, A total of 67 cycles were administered (median 3 cyc les, range 1-6), Overall response rate including disease stabilization which had been progressive under previous therapy was 68%, 10 patient s (40%, 95% CI 21-61%) achieved a partial remission, Seven responders had been progressive under previous therapy. Maximum responses were re ached 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), re spectively Four patients (16%) suffered from infections W.H.O. grade g reater than or equal to 2 (pneumonia grade 2, Staphylococcus septicaem ia grade 3, viral encephalitis and pneumonia, both grade 4 with comple te resolution). No other severe adverse events were observed. Cladribi ne given as s.c. 5 d bolus injections was found to he active in pretre ated Waldenstrom's macroglobulinaemia and resulted in durable remissio ns.