Rituximab-Bendamustine in First Line Treatment of Patients with Follicular Lymphoma. Results of Prospective Multicenter Study

BACKGROUND. Follicular lymphoma (FL) is lymphoid tumor that occurs in 22% of all non-Hodgkin's lymphomas (NHL) in Russia with median age 65 years. FL has a high chemosensitivity and often recurs: five-year progression-free survival (PFS) with R-CHOP - 40%. Due to high risk of recurrence and median age of FL pts 65 years, we need to reduce toxicity. Rituximab-bendamustine (R-B) versus R-CHOP in common group (without dividing on cytological grade) increases PFS and has lower toxicity, so it is possible to apply it to patients with concomitant pathology.

AIM. To study R-B efficiency in different cytological grade of FL.

PATIENTS AND METHODS. We performed a prospective, multicenter, open-label trial in Russia since 1 of June 2013 till 1 of June 2017. The study included 65 patients with FL. Median age of patients was 59 years (from 30 to 78 years). Treatment was completed in 60 patients, so this group of patients was analyzed. Ratio between men and women was 1: 2. 29/60 of patients (48%) were older than 60 y.o. Patients received rituximab 375 mg / m² on day 1 and bendamustine 90 mg / m² on days 1 and 2 of a 4-week cycle (6 cycles).

47/60 (78%) of pts were diagnosed with FL grade 1, 6/60 (10%) -2 grade, 7/60 (12%) - grade 3A. 55/60(91%) pts had nodular tumor growth type, 6/60(10%) - nodular-diffuse, 4/60 (7%) - diffuse. High risk according to FLIPI had 21/53 (39%) of patients with 1-2 cytologic grade of FL and 7/7 (100%) of pts with FL grade 3A.

Extranodal lesions were revealed in 23/60 (38%) of cases: in 4/60 of cases - orbit, in 2/60 - parotid gland, in 3/60 - lungs, in 3/60 - intestines, in 1 / 60 - stomach, 2/60 - pancreas, 2/60 - uterus, 2/60 - skin, 1/60 - subcutaneous tissue, 3/60 - vertebrae, in 1/60 - latticed maze and nasal passages. In 20/23 of cases extranodal lesion was revealed in generalized stage of FL (including lymph nodes and bone marrow).

Extranodal lesions were found in 35% of pts with FL grade 1-2, and 57% of pts with FL - grade 3A. Bulky also was observed more frequently in pts with FL grade 3 3/7 (43%) than in pts with FL grade 1-2 19/53 (36%).

Results. Complete remission (CR) of disease was achieved in 34/60 (55%) pts, partial remission (PR) - 13/60 (21%) pts. Tumor progression observed in 11/60 (18%) cases, pts were withdrawn from the protocol. In 2/60 (6%) pts had stable disease after 4 courses of R-B. Consequently we performed high-dose chemotherapy with autologous stem cell transplantation for patients with stable disease.

Frequency of CR and PR was higher in pts with FL grade 1-2 than in FL grade 3: 87% versus 28%. Progressive disease observed more frequently in FL grade 3A - 71% vs pts with FL grade 1-2 (13%). Median follow up was 42 (4-56) months. Bone marrow was sanitized in all cases of its lesion - 33/60 (55%).

Conclusions. 3A cytological grade of FL is associated with high FLIPI score, presence of bulky and extranodal lesions. These parameters are predictive unfavorable factors of poor response to R-B induction therapy. The R-B allows performing stem cells mobilization and autoSCT that is actual in FL pts with bone marrow involvement.