Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. 

The data described in Table 1 and the discussion below reflect exposure to Kepivance in 409 patients with hematologic malignancies who were enrolled in 3 randomized, placebo-controlled clinical trials and a pharmacokinetic study. Patients received Kepivance either before, or before and after, regimens of myelotoxic chemotherapy, with or without total body irradiation (TBI), followed by hematopoietic stem cell support. Kepivance was administered in daily doses ranging from 5 to 80 mcg/kg/day. The total dose of Kepivance ranged from 15 to 480 mcg/kg with a median of 360 mcg/kg. The population had a median age of 48 years (range: 41 to 60 years), 62% were male and 83% were White with 7.4 % Black and 6.2 % Hispanic. Non Hodgkin's lymphoma (NHL) was the most common malignancy followed by Hodgkin's disease, multiple myeloma, and leukemia. 

The most common adverse reactions attributed to Kepivance were skin toxicities (rash, erythema, edema, pruritus), oral toxicities (dysesthesia, tongue discoloration, tongue thickening, alteration of taste), pain, arthralgias, and dysesthesia. The median time to onset of cutaneous toxicity was 6 days following the first of 3 consecutive daily doses of Kepivance, with a median duration of 5 days. In patients receiving Kepivance, dysesthesia (including hyperesthesia, hypoesthesia, and paresthesia) was usually localized to the perioral region, whereas in patients receiving placebo dysesthesias were more likely to occur in extremities. 

The most common serious adverse reaction attributed to Kepivance was skin rash, reported in less than 1% (3/409) of patients treated. Grade 3 skin rashes occurred in 3% of patients (9/409) receiving Kepivance and 2% (5/241) receiving placebo. 

Cataracts: In a postmarketing safety study, the incidence of cataracts was numerically higher among patients receiving Kepivance than in the control population. (See 14 CLINICAL STUDIES). 

Infections: In a randomized, double-blind, placebo-controlled post-approval study designed to determine the efficacy of Kepivance with a high-dose melphalan preparative regimen, the incidence of treatment-emergent infections was significantly greater in patients treated with Kepivance compared to placebo. A total of 281 patients were randomized to 3 arms: Kepivance before melphalan on days -6, -5, -4 and after melphalan on days 0, 1, and 2 (pre-post) (n=115); Kepivance before melphalan on days -6, -5, -4 (pre) (n=109); or placebo (n=57). The incidence of reported infections were pre-post - 50%; pre - 47%; and placebo - 25% [see Clinical Studies ( 14.2)] . 

Laboratory Test Findings: Reversible elevations in serum lipase and amylase, which did not require treatment, were reported in 28% and 62% of patients receiving Kepivance and 23% and 54% of patients receiving placebo. In general, peak increases were observed during the period of cytotoxic therapy and returned to baseline by the day of hematopoietic stem cell infusion. Amylase was mainly salivary in origin.