Anti–B-cell monoclonal antibodies have been proven effective in B-cell post-transplant lymphoproliferative diseases (PTLDs; Benkerrou et al: Blood 92,3137, 1998). Other treatments, such as chemotherapy or antiviral drugs, are toxic or
AntiB-cell monoclonal antibodies have been proven effective in B-cell post-transplant lymphoproliferative diseases (PTLDs; Benkerrou et al: Blood 92,3137, 1998). Other treatments, such as chemotherapy or antiviral drugs, are toxic or ineffective. We report on the activity of rituximab (Rituxan) in 32 patients with B-PTLDs treated at 14 French centers.
There were eight liver, eight kidney, four heart, three lung, one heart/lung, one liver/kidney, one kidney/pancreas, and six bone marrow transplant (BMT) recipients. Median age was 34 years (range, 3 to 67 years), and median delay between graft and diagnosis of tumor was 5 months (range, 1 to 156 months). In organ recipients, tumors were classified as polymorphic and monomorphic in 10 and 15 cases, respectively; associated with Epstein-Barr virus (EBV) in 22 cases; and monoclonal in 10 of 12 tumors tested. Due to a rise in EBV load, fever, and lymph node enlargement, 4 of the 6 patients with BMT were treated without pathologic documentation. The immunosuppressive regimen was tapered in 27 patients.
Rituximab was used as first-line therapy in 30 patients and as salvage therapy in 2 patients. Median time between diagnosis and treatment was 14 days (range, 1 to 110 days). Eight infusions of rituximab were administered to 2 patients, four infusions to 26 patients, three infusions to 1 patient, and two infusions to 3 patients. The rituximab dose in each infusion in all cases was 375 mg/m².
Tolerance was good. The overall response rate (complete response [CR] plus partial response [PR]) was 69% (20 CRs; 2 PRs), with no difference between solid-organ recipients (15 CRs; 2 PRs) and BMT patients (5 CRs). Median time to response was 54 days (range, 11 to 148 days). With a median follow-up of 10 months (range, 3 to 19 months), 22 patients are alive and 18 patients are in CR.
Of the 22 responders, 4 (18%) relapsed and remain alive following salvage therapy, and 5 died (infection occurred in 3 patients; rejection in 1 patient; pulmonary fibrosis in 1 patient). Among the 10 patients in whom rituximab therapy failed, 5 died of B-cell PTLD and 5 are alive and well following salvage chemotherapy.
CONCLUSION: Rituximab appears to be a safe and relatively efficient therapy in B-cell PTLDs. These results need to be confirmed in an ongoing, prospective, multicenter trial.