Phase II study of rituximab after priming with IFN in patients with relapsed LG/F B-cell lymphoma

Rituximab mechanism of action includes CDC, ADCC and induction of apoptosis. The administration of IFN-a before and during Rituximab treatment could be effective in increasing antigen surface expression; further the immuno modulators effect of IFN-a, including stimulation of T-cell cytotoxicity and natural killer cell activity, might sinergize with the mechenism of action of Rituximab in inducing neoplastic clone suppression. In an ongoing open, non comparative, multicenter, Phase II Italian study, 63 relapsed LG/F NHL patiens, enrolled between May 97 and June 99, were treated with IFN+Rituximab. Treatment started with IFN-a, 1.5MU/day sc for the first week and then at 3 MU during second week. At day 15 patients received the first Rituximab injection at 375mg/sq, that was repeated at day 22, 29 an 36. IFN-a dose was maintained at 3 MU during the third week and than increased to 6 MU during fourth and fifth week. Patient characteristics included: median age 52 years (range 31-70 yr); male 30%; IWF: A 11%, B 27%, C 45%, D 17%; 80% stages III an IV; 53%, 29%, 18% of patients in 1st, 2nd and 3rd relapses, respectively. All patients had progressive disease, requiring therapy. By intent to treat analysis, the 58 patients evaluable for response obtained: CR 29%, PR 43% SD 14%, PD 4%, and dropouts 10%. Six out of the 17 patients who obtained CR are relapsed after 5, 12, 13, 15 and 16 months, respectively. The other 11 are still in CR after 2+ ® 24+ months of observation. Of the 25 PR patients, 4 were immediately treated with radiotherapy and/or chemotherapy and they are not evaluable for duration remission. Five out of the remaining 21 patients are relapsed after 1, 5, 8, 9, 12 months, respectively. The other 16 patients are still in PR after 2+ ® 22+ months. AEs, occurred in the 47 patients evaluable for toxicity, were primarily grade I and II, occurring with first Rituximab infusion. Nineteen patients required dose reduction of IFN. The most frequent treatment related AEs were: fever, neutropenia, transaminases increase, nausea, chills, hypertension, thrombocytopenia and vomiting. Ten patients (21%) had grade III and 3 (6%) grade IV AEs. This interim analysis suggests that combination immunotherapy with IFN-a and Rituximab is more effective than Rituximab alone, but the AEs rate increases (72% ORR versus 48% and 27% grade III and IV AEs versus 15%, observed in the pivotal study).