Front-line high-dose chemotherapy (HDT) combined with rituximab for adults with aggressive large B cell lymphoma (DLBCL). A pilot study by the GOELAMS

Abstract

6662 Background: The beneficial effect of adding rituximab to CHOP has been shown for elderly patients with DLBCL (Coiffier et al NEJM 2002). We have shown that HDT with autologous stem cell transplantation is superior to CHOP in young adults with DLCL (Milpied et al NEJM in press). The feasibility of adding rituximab to front-line HDT remains to be established. Methods: A prospective pilot trial was proposed to patients with DLBCL, with intermediate-high or high age-adjusted IPI, up to the age of 60 y.o. This program consisted of 2 courses of high-dose CHOP-like regimen, 15 days apart, with rituximab (375 mg/ m2) on d1 of each course, followed by rituximab on d 22, harvest of peripheral blood stem cells (G-CSF mobilized) on days 28,29, then rituximab on d 36 followed by a course of high-dose methotrexate with cytarabine and by a BEAM regimen starting on d 66 to 80, followed by the infusion of stem cells. Results: Between 04/2002 and 05/2003, 41 consecutive patients gave their informed consent and were included in that trial. Their median age was 50y.o.( 18–60 yo); 23 had WHO PS >/= 2, the LDH level was > N in 37 patients and 38 had Ann Arbor stage III or IV. The age-adjusted IPI was intermediate-high in 21 and high in 19 patients.At the time of this abstract, the program has been completed in 75% of the patients. Three patients died of toxicity of the treatment before the BEAM regimen and autologous transplantation. On an intent-to-treat basis, the response rate at the end of the treatment was CR/CRu= 64%, PR=8%, failure to achieve a response or progression= 20% and toxic death=8%. No toxic death was directly attributable to the addition of rituximab. Conclusions: The addition of 4 doses of rituximab to this HDT program is feasible with no unexpected toxicity, allows the harvesting of sufficient numbers of stem cells to allow an autologous transplantation following a BEAM regimen in responding patients . Follow-up and comparison with historical control will be performed and presented Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Pharmaceutical Roche France