Improved Survival of Intravascular Large B-Cell Lymphoma (IVLBCL) by Rituximab Containing Combination Chemotherapies.

Abstract Background: Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of extranodal diffuse large B-cell lymphoma (DLBCL) with poor prognosis. Recently, the addition of rituximab to CHOP regimen has significantly improved the outcome of DLBCL. However, the efficacy of rituximab in IVLBCL remains unclear. Objective and Patients: To evaluate the usefulness of rituximab in IVLBCL, 70 patients who were diagnosed as IVLBCL between 1999 and 2007 from the 16 participating centers were retrospectively analyzed. Patient characteristics were as follows: median age, 68 yrs (range, 34 to 88 yrs); sex, M/F 56%/44%; LDH > UNL, 99%; stage III/IV, 100%; extranodal site > 1, 81%; PS > 1, 84%; IPI: H-I/H, 97%. Sixty four of 70 patients received anthracycline containing chemotherapies. In 64 patients, 43 (67%) and 21 (33%) patients received rituximab containing chemotherapies (R-chemo) and chemotherapies without rituximab (chemo), respectively. There was no significant difference between the two groups in terms of various clinical variables. Results: The complete response rate (%CR) was significantly higher in the R-chemo group than in the chemo group (90% vs. 55%, P = 0.0003). With a median follow up time of 24 months (range, 2 to 88 months) in living patients, 2-year progression-free and overall survival (OS) rates were significantly higher in the R-chemo group than in the chemo group (63% vs. 32%, 71% vs. 39%, P = 0.015 and 0.01, respectively). In univariate analysis, age, LDH, the number of extranodal site, PS and platelet count were not significant prognostic factor, while the use of rituximab was favorably associated with OS (HR, 0.33; 95% CI, 0.13 to 0.88; P = 0.015). Grade 3 hypoxia due to the infusion of rituximab was observed in one of 43 patients (2%). Grade 3 or 4 non-hematologic adverse events were observed in the 3 of 43 (7%) patients and 3 of 21 (14%) patients, respectively. Treatment related death was observed in 3 patients. Two in the R-chemo group died of HBV reactivation and tuberculosis, and one in the chemo group died of sepsis. Eight of 43 and 12 of 21 patients in the each group died at the time point of the study, respectively, and the most major cause of death was primary disease (6 and 11 patients, respectively). Conclusion: Our data strongly suggested that the addition of rituximab to chemotherapies significantly improved the %CR and survival in IVLBCL without significant increase in toxicities. Thus, prospective clinical trials of rituximab-containing chemotherapies for IVLBCL are warranted.