R-CHOP Found Superior in Grade 3A, 1-2-3A Follicular Lymphoma

A new retrospective analysis has suggested that the R-CHOP chemotherapy regimen of rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone leads to superior outcomes compared to rituximab plus bendamustine in patients with grade 3A follicular lymphoma.

A new retrospective analysis has suggested that the R-CHOP chemotherapy regimen of rituximab (Rituxan), cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone leads to superior outcomes compared to rituximab plus bendamustine (R-B) in patients with grade 3A follicular lymphoma (FL).

The new data, published in the Annals of Hematology,1 fills an important research gap, since relatively little data so far has been published to guide therapy decisions for patients with FL3A.

Grade 3 FL is divided into 2 subcategories, the difference being the presence (3A) or absence (3B) of centrocytes. Recent literature has also suggested that grade 1-2 and 3A FL frequently coexist in a single tissue specimen (FL1-2-3A).

Corresponding author Christian W. Scholz, MD, of Vivantes Hospital, in Germany, and colleagues noted that FL often comes with a promising prognosis following chemoimmunotherapy.

Patients with FL1-2 who have a high tumor burden typically find success receiving either CHOP or bendamustine plus an anti-CD20 antibody, such as rituximab. Patients with FL3B typically receive R-CHOP. The investigators said histologic grading can be challenging, but it plays an important role in treatment decisions and ultimately in prognosis. However, the decision-making process is more difficult when it comes to FL3A.

“Whether FL3A should be treated like indolent or aggressive lymphoma is currently uncertain,” the study authors wrote. “To date, there are no results from prospective randomized clinical trials, and only data from two retrospective analyses are available.”

The new study adds to the scientific literature by reporting on the experiences of 95 patients who met the World Health Organization’s criteria for FL3A (based on a biopsy), who were at least 18 years old, and who required systemic treatment. The patients were treated between the years 2001 and 2017.

The data set included 66 patients with FL3A, and an additional 29 patients who had coexisting 1-2 and 3A FL in a single specimen. Members of the latter group were graded as FL1-2-3A.

The 95 patients were given either R-CHOP (n = 59) or R-B (n = 36) regimens. The FL3A and FL1-2-3A patients were equally distributed between the 2 treatment cohorts. Patients were given a median of 6 cycles of chemoimmunotherapy, beginning a median of 1 month following diagnosis. Only 2 patients had undergone radiotherapy for local disease prior to chemoimmunotherapy.

Fifty-two percent of patients (48% on R-CHOP and 52% on R-B) were given maintenance therapy. Most patients were given rituximab for maintenance, and a median of 8 cycles of maintenance therapy were given to the R-CHOP cohort. In the R-B cohort, a median of 5 cycles of maintenance therapy were given.

In both the FL3A and FL1-2-3A cohorts, Scholz and colleagues reported that patients who received R-CHOP had a higher response rate and longer overall survival (OS) compared to those who received R-B. In terms of response rate, R-CHOP beat R-B 95% to 76% (P = .003). The 3-year OS rate was 89% with R-CHOP treatment versus 73% in patients who received R-B (P = .008). There was no statistically significant difference between the 2 cohorts when it came to progression-free survival (PFS).

Scholz and colleagues reported that transformation rates into aggressive lymphoma were similar between the 2 groups, though there were more additional malignancies in the R-B group (n = 6) versus the R-CHOP group (n = 2).

The authors also included 203 patients with FL1-2 in their analysis. Of those, 98 received R-CHOP and the remaining 105 received R-B. In these patients, the authors reported R-B had a superior 3-year PFS rate (79% vs 47%), but that did not translate into statistically significant differences in either OS or transformation.

Scholz and colleagues noted that their findings differ significantly from a previous study by Mondello et al,2 which did not find a difference in OS between R-CHOP and R-B, and which also found a notable PFS advantage for R-B. One difference between the studies, however, was that Mondello and colleagues only analyzed patients with FL3A and did not include FL1-2-3A patients, as was the case in the current study. Scholz and colleagues said the differences between their findings and other studies may have to do with the heterogeneity of FL3A and FL1-2-3A.

The investigators concluded that their findings support the use of R-CHOP, though they said a prospective trial that could confirm their findings is “highly desirable.”

In the meantime, they said factors aside from therapy choice are also important determinants of patient prognosis.

“Apart from the choice of therapy, transformation into aggressive lymphoma and whether the patient reached a complete or partial response were independent risk factors for OS in a multivariate analysis,” they wrote.


1. Pouyiourou M, Meyer A, Stroux A, et al. First-line treatment with R-CHOP or rituximab-bendamustine in patients with follicular lymphoma grade 3A-results of a retrospective analysis. Ann Hematol. Published online July 30, 2020. doi:10.1007/s00277-020-04171-7

2. Mondello P, Steiner N, Willenbacher W, et al. Bendamustine plus rituximab versus R-CHOP as first-line treatment for patients with follicular lymphoma grade 3A: evidence from a multicenter, retrospective study. Oncologist. 2018;23(4):454-460. doi:10.1634/theoncologist.2017-0037