Rituximab Added to Aggressive Chemotherapy Improves the Outcome of Patients with Follicular Lymphoma, Grade 3 and Results In Survival Comparable to Diffuse Large B-Cell Lymphoma.
Authors: Bierman Philip J. , Vose Julie M. , Bociek R. Gregory , Loberiza Fausto R. , Bast Martin , Armitage James O. 
Published: October 2019

Abstract
Abstract 2810
The survival of patients with diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma is improved when rituximab is combined with chemotherapy. However, little is known about the outcome of patients with follicular lymphoma, grade 3 (FL-3), since these patients are generally excluded from DLBCL trials and often from trials evaluating treatment of follicular lymphoma. We therefore performed a retrospective study to evaluate the results of rituximab-based therapy for FL-3. An analysis of the Nebraska Lymphoma Study Group database allowed us to identify patients with FL-3 who were treated with aggressive combination chemotherapy regimens with and without the addition of rituximab. The progression-free survival (PFS) and overall survival of these patients were compared to patients with DLBCL who were treated with similar aggressive chemotherapy regimens combined with rituximab. Patients who were not treated with anthracycline-containing or mitoxantrone-containing regimens were excluded from analyses. We identified 60 FL-3 patients who were treated with aggressive chemotherapy regimens, combined with rituximab, between Feb. 1999 and Jan. 2009. The median age was 56 years (range 37–87 years). There were 27 males and 33 females. The performance status was 0–1 in 80%, the LDH was elevated in 15%, 68% had stage III-IV disease, and 13% had at least 2 sites of extranodal disease. Fifteen patients (25%) had bulky disease (≥5 cm) at diagnosis. The results of treatment for these patients were compared to 144 FL-3 patients treated with aggressive chemotherapy regimens without rituximab between June 1983 and Jan. 1999, and to 341 patients with DLBCL who were treated with aggressive chemotherapy regimens combined with rituximab between Sept. 1996 and Jan. 2009. The treatment outcomes for these three groups of patients are displayed in the table.
5-yr Estimate (95% CI) 8-yr Estimate (95% CI) Log-Rank p-value Progression-Free Survival 0.04 FL-3 with rituximab 65% (50–77) 45% (23–65) FL-3 without rituximab 42% (34–50) 33% (26–41) DLBCL with rituximab 53% (47–58) 47% (40–54) Overall Survival 0.06 FL-3 with rituximab 85% (72–92) 71% (54–82) FL-3 without rituximab 68% (59–74) 54% (46–62) DLBCL with rituximab 64% (58–69) 56% (48–63)
A multivariate analysis (accounting for older patients, and more patients with elevated LDH, extranodal disease, and bulky disease in the DLBCL group) revealed that patients with FL-3 who were not treated with rituximab had a significantly higher risk of disease progression or death (RR 1.75; p=0.02). There were no significant differences in PFS when comparing patients with FL-3 and those with DLBCL who were treated with aggressive chemotherapy regimens and rituximab. Follicular lymphoma, grade 3 patients treated without rituximab had inferior overall survival, when compared to patients treated with rituximab (RR 1.58), although this difference was not significant (p=0.16). The multivariate analysis also revealed no significant differences in survival when patients with FL-3 who received rituximab were compared to similarly treated patients with DLBCL (p=0.50). In conclusion, this analysis demonstrates that the outcome of treatment for patients with FL-3 who are treated with aggressive chemotherapy regimens is improved when rituximab is added to therapy. In the “rituximab era” the outcome of patients with FL-3 is comparable to DLBCL.

Disclosures:
Vose: Millennium Pharmaceuticals, Inc.: Research Funding.