CLINICAL STUDIES

The following table provides efficacy results for 4 groups (columns) of patients with hairy cell leukemia: patients who initially received NIPENT, patients who initially received alpha-interferon (IFN), and 2 different groups of patients who received NIPENT after proving to be refractory to, or intolerant of IFN therapy. The first 2 groups represent treatment results from the SWOG 8691 study, a large multicenter study comparing NIPENT and IFN in untreated (frontline) patients with confirmed hairy cell leukemia. The third group represents evaluable patients from the SWOG study who crossed over to NIPENT after initially receiving IFN. The fourth group, labeled NCI Phase 2 studies, displays pooled results of 2 noncomparative studies (MD Anderson and CALGB), in which NIPENT was used to treat patients with confirmed IFN-refractory disease.

In the SWOG 8691 study, NIPENT was administered at a dose of 4 mg/m2 every 2 weeks. After 6 months of treatment, patients were evaluated for response. If a complete response was achieved, 2 additional doses of NIPENT were administered and then discontinued. If a partial response was achieved, NIPENT was continued for up to an additional 6 months. NIPENT was discontinued for stable disease after 6 months or progressive disease after 2 months of therapy. IFN was administered 3 million units subcutaneously 3 times per week. Patients who achieved a complete or partial response after 6 months of treatment continued on IFN for another 6 months. IFN was discontinued if patients did not achieve a complete or partial response after 6 months of initial treatment or progressed after 2 months. This study allowed crossover of patients intolerant of, or refractory to, initial treatment.

Interferon-refractory patients enrolled into the MD Anderson study received NIPENT at a dose of 4 mg/m2 every other week for 3 months and responding patients received 3 additional months. CALGB patients received 4 mg/m2 of NIPENT every other week for 3 months and responding patients were treated monthly for up to 9 additional months. Almost all patients had a PS of 0 to 2 in the Phase 2 and 3 studies.

For each study, a complete response (CR) required clearing of the peripheral blood and bone marrow of all hairy cells, normalization of organomegaly and lymphadenopathy by physical examination, and recovery of hemoglobin to at least 12 g/dL, platelet count to at least 100,000/mm3, and granulocyte count to at least 1500/mm3. A partial response (PR) required that the percentage of hairy cells in the blood and bone marrow decrease by more than 50%, enlarged organs and lymph nodes decrease by more than 50% by physical examination, and hematologic parameters had to meet the same criteria as for complete response. The table below reports the response rate for 2 groups of patients: (1) Evaluable, i.e., patients who could be evaluated for response and (2) Intent-to-Treat, i.e., patients diagnosed with hairy cell leukemia.

The results show that frontline patients treated with NIPENT achieved a significantly higher rate of response than those treated with IFN. The time to recovery of neutrophil and platelet counts was shorter with NIPENT treatment and the estimated duration of response was longer. The response rate in IFN-refractory patients treated with NIPENT was similar to that in NIPENT-treated frontline patients. At a median follow-up duration of 46 months, there was no statistically significant difference in survival between hairy cell leukemia patients initially treated with NIPENT and those initially treated with IFN. However, no definite conclusions regarding survival can be made from these results because they are complicated by the fact that the majority of IFN patients crossed over to NIPENT treatment.

In the Phase 3 SWOG study, 25 patients with hairy cell leukemia died during treatment or follow-up: 18 patients had last received NIPENT (3 of whom had crossed over from IFN), and 7 patients had last received IFN (1 of whom crossed over from NIPENT). Eleven of the 25 deaths occurred within 60 days of the last dose of treatment. Of these, hairy cell leukemia was cited by the investigators as a contributory cause for 1 death in the NIPENT group and 3 deaths in the IFN group. Additionally, infection contributed to the deaths of 3 patients in the NIPENT group and 2 patients in the IFN group. Approximately 4% of hairy cell leukemia patients, in each arm, died more than 60 days after the last dose of either treatment and there was no outstanding cause of death among these patients.