Rituximab(Drug information on rituximab) (Rituxan) is active in low-grade non-Hodgkins lymphoma (NHL), but its efficacy in poor-prognosis intermediate-grade NHL is unknown. To address this issue, we administered rituximab to seven patients with CD20-positive diffuse large cell NHL who had progressive disease despite high-dose therapy and peripheral stem-cell transplantation (PSCT). The median age was 59 years (range, 45-62 years) with ECOG performance status 0-1. Prior to rituximab therapy, all patients had undergone PSCT, with responses of two complete responses (CRs), two partial responses (PRs), one patient with stable disease (SD), and two patients with progressive disease (PD). The CRs lasted 9 and 11 months. Upon relapse or progression of disease, the patients received 4 weekly infusions of rituximab (375 mg/m²).
Acute complications consisted of rash and rigors in one patient during the first infusion only. Delayed adverse events included three episodes of transient granulocytopenia (absolute neutrophil count [ANC] nadir, 48, 644, and 1,394), occurring from day 74 to day 112, resulting in one hospitalization for neutropenic fever.
Of the five patients who were initially symptomatic from their NHL, two had complete resolution of and three had improvement in their symptoms by the completion of the 4-week course. At initial restaging (day 48-79) after initiation of therapy, 6 of 7 patients responded (1 CR and 5 PRs) and one patient had SD. Two patients (1 SD and 1 PR) later developed progressive disease at day +60 and +87, respectively, and underwent retreatment with rituximab, with responses of CR and PD, respectively. Maximum response achieved was 3 CRs and 4 PRs. Six of seven patients achieved a performance status of 0. With median follow-up of 215 days (range, 117-270 days) from initiation of therapy, and with 2 patients having undergone retreatment, there currently are 2 CRs, 2 PRs, and 3 patients with PD (mixed response). The incidence of granulocytopenia, while significantly higher than that seen with rituximab in low-grade NHL, was transient and lower than that expected with conventional salvage chemotherapy.
CONCLUSION: Rituximab appears to have significant activity and is well tolerated in patients with progressive intermediate-grade NHL after PSCT.