Follicular lymphoma: first - line selection criteria of treatment

Abstract

Follicular lymphoma (FL) is a tumor that develops from the B cells of the germinal center; characterized by recurrent and remitting course of the disease, the transformation of a tumor into diffuse large B-cell lymphoma (DLBCL) is possible. In generalized lesions and progression of FL, the most commonly used courses are R-CHOP and R-B. The choice of therapy for different cytological types, clinical and laboratory parameters remains disputable. Aim. To analyze the clinical, laboratory, morphological parameters of patients with FL, who got R-B and R-CHOP therapy; determine the criteria for selecting induction therapy. Materials and methods. The study included 203 patients with FL from 2000 to 2018. R-CHOP treatment was initiated in 126 patients, 14 of whom later received high - dose therapy (HDT) (R-DHAP: rituximab, dexamethasone, cisplatin, cytarabine) without autologous stem cell transplantation (autoSCT), 21 - HDT with autoSCT; treatment of 89 patients was limited to courses of R-CHOP and maintenance therapy with rituximab, two patients (in whom the disease progressed, despite R-CHOP therapy) were assigned the mNHL-BFM-90 program. The efficacy of treatment on various treatment regimens was evaluated primarily by overall survival. Results and discussion. R-B. 77 patients received R-B therapy. Complete remission of the disease was achieved in 47/77 (61%) patients (3 of them later developed a relapse of the disease), partial remission was achieved in 15/77 (19%) patients, in 13/77 (17%) cases progression was recorded tumors. 70 patients had 1-2 cytological type of tumor, 6 patients - 3A cytological type. In cases of progression, 3 of 13 patients (46%) were diagnosed with 3A cytological type FL. Median observation (at the time of analysis) - 34 months. R-CHOP. 89 patients with FL received high - dose therapy with R-CHOP (6-8 courses) and maintenance therapy with rituximab. In 39 (44%) patients, the disease remained in remission, and in 50 (56%), a relapse of the disease developed. 50 patients had 1-2 cytological types, 39 - 3 cytological types. In cases of recurrence of FL, a 3A cytologic type (36%) was diagnosed in 18/50 patients. Median observation - 93 months. R-CHOP + HDT and autoSCT. 21 patients after the R-CHOP courses continued (due to insufficient antitumor response) high - dose chemotherapy (HDT) and auto-SCT were performed. In 18/21 (86%) cases, complete remission of the disease was achieved and maintained, in 3 (14%) cases relapse developed. 16 patients had 1-2 cytological types, 5 - 3 cytological types. Median observation - 81 months. R-CHOP + HDT without autoSCT. 14 patients started therapy under the R-CHOP program as induction therapy, but then (due to insufficient antitumor response), the treatment was continued according to the HDT without autoSCT. 11 (79%) patients are currently in remission of the disease, in 3 (21%) - there was a relapse. 10 patients had 2 cytological types of PL, 4 - 3 cytological types. 11 (79%) patients are currently in remission of the disease, in 3 (21%) - there was a relapse. Median observation - 80 months. 7-year OS of patients with FL on RB therapy was 89% (95% CI 75-99), on R-CHOP therapy - 85% (95% CI 73-90), on R-CHOP + HDT and autoSCT - 87% (95% CI 57-100), on R-CHOP + HDT without autoSCT - 82%. 7-year PFS of FL patients on RB therapy was 70% (95% CI 75-99), on R-CHOP therapy - 44% (95% CI 73-90), on R-CHOP + HDT and autoSCT - 74% (95% CI 57-100), on R-CHOP + HDT without autoSCT - 80%. Conclusion. The R-B is most effective in FL 1 and 2 cytological types. The cytological type does not correspond to the type of tumor growth: at 3A and 3A + 3B cytological types, nodular / nodular - diffuse and diffuse types of growth are found. When choosing an induction course, one should look at the cytological type of FL. A high proliferative activity index (according to Ki67) is a predictor of resistance to R-B therapy. The absence of an interfollicular T-cell reaction in tumor tissue FL is associated with tumor chemoresistance. The presence of the bulky factor is associated (in most patients) with the FLIPI index with values from 3 to 5, and is a predictor of a poor response to therapy. Patients with bulky, high (more than 35%) Ki67 index and FLIPI from 3 to 5 in the debut of the disease as the first line therapy, it is preferable to choose the R-CHOP mode, and in the absence of (after 4-6 courses) to complete or partial remission to continue conducting the HDT.

About the authors

E S Nesterova

National Research Center for Hematology

Email: nest.ek@yandex.ru
к.м.н., н.с., врач-гематолог отд-ния интенсивной высокодозной химиотерапии гемобластозов с дневным и круглосуточным стационаром Moscow, Russia

S K Kravchenko

National Research Center for Hematology

к.м.н., зав. отд-нием интенсивной высокодозной химиотерапии гемобластозов с дневным и круглосуточным стационаром Moscow, Russia

A M Kovrigina

National Research Center for Hematology

д.б.н., зав. патологоанатомическим отд-нием Moscow, Russia

E G Gemdzhian

National Research Center for Hematology

с.н.с. лаб. биостатистики; ORCID: 0000-0002-8357-977x Moscow, Russia

L V Plastinina

National Research Center for Hematology

к.м.н., врач консультативно-гематологического отд-ния с дневным стационаром по проведению интенсивной высокодозной химиотерапии Moscow, Russia

F E Babaeva

National Research Center for Hematology

аспирант отд-ния интенсивной высокодозной химиотерапии гемобластозов с дневным и круглосуточным стационаром Moscow, Russia

T N Obukhova

National Research Center for Hematology

к.м.н., зав. лаб. кариологии Moscow, Russia

A U Magomedova

National Research Center for Hematology

д.м.н., в.н.с. отд-ния интенсивной высокодозной химиотерапии гемобластозов с дневным и круглосуточным стационаром Moscow, Russia

T V Gaponova

National Research Center for Hematology

к.м.н., зам. ген. директора по трансфузиологии, зав. отд. процессинга клеток крови и криоконсервирования Moscow, Russia

A M Kremenetskaya

National Research Center for Hematology

зав. отд-нием интенсивной высокодозной химиотерапии гемобластозов с дневным и круглосуточным стационаром Moscow, Russia

A I Vorobyev

National Research Center for Hematology

академик РАН, рук. отд-ния химиотерапии и интенсивной терапии гематологических заболеваний Moscow, Russia

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