Rituximab Plus Anthracycline-Based Chemotherapy Prolongs Survival Long-Term in Follicular Lymphoma

Rituximab (Rituxan) added to standard anthracycline-based chemotherapy demonstrated significant improvements in progression-free survival (PFS) as well as overall survival (OS) as treatment of patients with follicular lymphoma (FL), according to 35-year follow-up results of patients treated through the Nebraska Lymphoma Study Group.

The analysis of rituximab plus standard anthracycline-based chemotherapy in FL looked at the impact of prognostic factors on survival. Patients were stratified by their age, histological subtype, Follicular Lymphoma International Prognostic Index (FLIPI) scores, tumor grades, treatment regimens, and the presence of a secondary malignancy.

A total of 1037 patients were included in the study, of whom all were diagnosed with FL between 1982 and 2020. Using a Kaplan-Meier analysis, PFS and OS were analyzed and were pre-specified as statistically significant at a P value of .05.

The median age in the study population was 51 years (range, 17-91). FL-2 was the most prevalent histologic subtype (30.2%), followed by FL-3A in 27.3%, FL-1 in 23.1%, and FL-3B in 2.5%. The remaining 16.9% of patients had composite lymphoma. In terms of treatment, 43.8% of patients received an anthracycline-based regimen without rituximab, while 24.5% received anthracycline plus rituximab, and 10.6% of patients received neither agents.

, and rituximab only was given to 9.8% of patients. The treatment regimen was unknown for 11.3%. The FLIPI category was high risk for 9.1% of patients, low risk for 33.6% of patients and intermediate for 38.8% of patients. FLIPI information was not available for 19.6% of patients.

Results showed that the addition of rituximab to standard anthracycline-based chemotherapy led to a median PFS of 4.6 years. Observation of PFS according to stratification factors showed that patients with a low FLIPI score had a longer PFS of 8.6 years compared with 3.6 years for subjects with intermediate-risk disease and 2.1 years in the high-risk group.

In terms of treatment regimen, individuals who received both rituximab and standard anthracycline-based chemotherapy had a significantly longer PFS of 10.6 years compared with just 5.3 years in patients who received rituximab alone and 3.05 years in patients who only received an anthracycline based regimen (P < .001).

Finally, histologic subtype PFS assessment showed that patients with FL-3B histology fared better in comparison with the other subtypes. Specifically, patients FL-3B had a 9.2-year PFS. The PFS observed for patients with FL-3A was 5.2 years versus only 4.7 years among patients with FL-1 disease and 4.2 years for patients with FL-2 (P =0.24).

Rituximab added to standard anthracycline-based chemotherapy also prolonged OS to a median of 12.1 years. Overall, the PFS with rituximab was 16.1 years versus 9.89 years without rituximab. Looking at FLIPI score, patients with low-risk disease had a lengthier PFS of 15.1 years compared with 11.7 years in the intermediate-risk group and 4.9 years in the high-risk group. The evaluation of OS according to histologic subtype showed n OS of 10.8 years for patients with FL3A, 11.6 years for those with FL-3B, and 14.3 years for both the FL-2 and FL-1 subgroups (P =0.081). OS was also significantly higher among patients who received a rituximab and anthracycline therapy (18.8 years) versus 11.3 years in those who received rituximab only 9 years in anthracycline-based therapy group (P <0.001).

After efficacy was analyzed in the study, secondary malignancies were identified in 6.75% of the patient population. Of the secondary malignancies observed, 11 patients had myelodysplastic syndrome, 10 had acute myeloid leukemia, and 9 patients had lung cancer.

In the extended follow-up study, 190 patients either relapsed or died after 10 years. Of the deceased patients, 13.7% died of relapsed lymphoma, 55.8% of unknown causes, 4.2% succumbed to a secondary malignancy, and death was treatment-related for 2.6% of patients. The remaining 23.7% were not related to disease.

Notably, 29.7% of the study population had not relapsed at a median follow-up of 9.2 years and maximum of 36 years.

Based on the results from this study, investigators led by Amulya Yellala, MBBS, of the University of Nebraska Medical Center noted that late relapse can occur with rituximab plus standard anthracycline-based chemotherapy, and physicians should also consider the possibility of secondary malignancies for these patients with FL.

_Reference:

_{Yellala A, Lyden ER, Nutsch H, et al. Thirty-five year follow-up analysis of follicular lymphoma patients treated through the Nebraska Lymphoma Study Group: Prognostic factor analysis and outcomes. Blood. 2020;136(supp 1);7-8. doi: 10.1182/blood-2020-142743}