Efficacy Controls and Long-Term Follow-Up of Patients (Pts) Treated with FC Plus Rituximab for Relapsed Follicular NHL. Session Type: Publication Only

Although treatment of follicular lymphomas (FL) with standard chemotherapy regimens generally yields a high initial response rate, the clinical course consists of a pattern of repeated relapses.Subsequent responses after every new line of treatment are of progressively shorter duration and the patients eventually die of disease-related causes. The ability of Rituximab to sensitize cell lines to fludarabine, doxorubicine, vinblastine, and cisplatin together with the synergism of Rituximab with CHOP in the treatment of DLBCL, was recently reported .We have completed in April 2003 a multicenter Phase II clinical trial in 52 pts with relapsed FL. Patients received chemotherapy consistent of Fludarabine 25 mg/sqm/die and Cyclofosfamide 30 mg/sqm/die for 3 consecutive days every 3 weeks for 4 cycles. Rituximab was infused on day 1 of every cycles at a dose of 375 mg/sqm. Patient characteristic: median age 62 years (range: 44-80); disease stage: I -II B 21%, III 30%, IV 49%; number of prior chemotherapy regimens:1- 43%, 2-43%, 3-12%, 4-3%. The response rates in the intent to treat analysis is: CR 75 % (39 pts), PR 19% (10 pts) and dropouts 6% (3 pts).Of note, 58% of the pts initially bcl-2 positive in the bone marrow became bcl-2 negative following treatment.At a median follow-up of 20 months, the restricted media duration of response in the 49 pts who have obtained a response was 26 months (95% CI, 22-29). Included in the group of this 49 pts assessed for duration of response were 6 pts who had achieved a PR and a CR but whose bone marrow remained bcl-2 positive. These pts were treated with a subsequent course of 4 doses of Rituximab plus IFN-a 3 MU t.i.w for 6 weeks.Approximately 93% experienced treatment-related toxicity; however, the majority of side effects were grade 1 / 2. The most common severe adverse events were hematologic, and included 20 cases of grade 3/ 4 neutropenia, 1 case of thrombocytopenia, and 3 cases of anemia as well as infection. Five patients died during the treatment period and follow-up: 1 of myelodysplastic syndrome, 2 of disease progression, 1 of progressive carcinoma, and 1 of pneumonitis.Treatment delays of 1-3 weeks were necessary in 12 pts. Treatment interruptions were necessary in 3 pts, 1 following cycle 2 and 2 following cycle 3.The results of our trial demonstrate that this regimen is active and relatively well tollerate although significant cytopenia with delay of subsequent treatment administration was observed in several pts.Finally, a DR of 26 months after a median follow-up of 20 months compare favorably with the results obtained in other trial in similar subset of pts and support the evidence for Rituximab plus chemotherapy as a new standard for treating relapsed FL