Contributions
Abstract: EP564
Type: E-Poster Presentation
Session title: Aggressive Non-Hodgkin lymphoma - Clinical
Background
High-grade B-cell lymphoma double-hit (HGBL DH) can arise from follicular lymphoma (FL). In the case of transformation of FL it accumulates a large number of additional mutations and secondary c-MYC gene rearrangement, which can make it resistant to standard immunochemotherapy.
Aims
To evaluate an efficacy of induction regimen R-CHOP/R-DA-EPOCH and modified BFM chemotherapy with rituximab in treatment of HGBL DH raised from FL.
Methods
We studied 13 FL pts with double- (9 - with с-MYC/8q24 and BCL2/18q21; 4 - with с-MYC/8q24 and BCL6/3q27) and one pt with triple translocations involving c-MYC/8q24, BCL2/18q21 and BCL6/3q27 genes and deletion of 17p13. 10 pts had morphological signs of transformation into aggressive lymphoma; 4 pts had FL 3A. There was 8 women and 6 men aged from 30 to 60 y. o. (median 47 y.o.). Lymph node with the highest FDG-accumulation according to PET-CT was chosen for biopsy and consequent immunohistochemistry and cytogenetics.
The majority of pts had high 12/14 and 2/14 - high-intermediate FLIPI score. All pts had advanced (III-IV) stage according to Ann-Arbor classification. 3 out of 14 pt had a history of low-grade FL (16-96 months) without c-MYC rearrangement in primary biopsy samples, in other 11 cases - anamnesis varied from 0,5 to 4,0 months. Lymphoma manifested by rapidly spread aggressive tumor with bulky disease: 2 pts had leukemic presentation of FL; 1 pt had FL cells in cerebrospinal fluid; 12/14 out of pts had several extranodal sites of involvement such as ovaries (2/8), kidneys or adrenals (6/14), paranasal sinuses (1/14); bones (3/14); soft tissues (4/14); lungs (3/14); stomach or intestine (4/14); spleen (4/14); liver (1/14). Ki-67 varied from 40 to 90%. An expression of c-MYC protein higher than 40% in 11/13 of FL pts. We didn’t revealed TP53 mutation within 7 out of 7 analyzed pts.
Results
None of pts had previous therapy. 4 pts were treated with R-CHOP-21. 3/4 (75%) out of pts died due to progressive disease (PD), 1/4 (25%) had partial remission (PR) after consequent therapy including obinutuzumab. 7 pts underwent modified BFM-protocol with Rituximab. 6/7 (86%) out of pts achieved complete remission (CR) after first-line treatment, 1 pt died due COVID-19 in PD status (14%). Autologous stem cell transplantation (auto-SCT) was performed in 4 out of 7 pts. 3 pts underwent R-DA-EPOCH. 1 pt achieved a CR after 6 courses, 1 pt - after second-line 2 R-DHAP; auto-SCT was performed for consolidation. 1 pt (33%) had PD after R-DA-EPOCH and another therapy. Rituximab supportive treatment was administrated only in 4 cases due to epidemiological situation. Median of observation was 9 months (1,0-59,5). We couldn’t study TP53 mutation status in pts with PD, but we observed PD in one case with deletion of 17p13.
Conclusion
For better diagnostics of FL transformation into HGBL DH we should perform biopsy of lymph node with the most active FDG accumulation according to PET-CT. We observed a higher rate of CR in this pts cohort when treated with intensive induction immunochemotherapy (modified BFM chemotherapy with rituximab) in comparison with R-CHOP/R-DA-EPOCH (86% vs 25% and 33%, respectively), and lower rate of primary resistance/PD (14% vs 75% and 33%). Our data needs consequent confirmation or consideration within metanalysis due to rare diagnostics of FL with double translocations of c-MYC and BCL2/BCL6. We should initiate a randomized study to estimate if auto-SCT had any benefits in comparison with a new immunotherapy modalities in FL transformed into HGBL DH.
Keyword(s): C-myc, Follicular lymphoma, High dose therapy, Transformation
Abstract: EP564
Type: E-Poster Presentation
Session title: Aggressive Non-Hodgkin lymphoma - Clinical
Background
High-grade B-cell lymphoma double-hit (HGBL DH) can arise from follicular lymphoma (FL). In the case of transformation of FL it accumulates a large number of additional mutations and secondary c-MYC gene rearrangement, which can make it resistant to standard immunochemotherapy.
Aims
To evaluate an efficacy of induction regimen R-CHOP/R-DA-EPOCH and modified BFM chemotherapy with rituximab in treatment of HGBL DH raised from FL.
Methods
We studied 13 FL pts with double- (9 - with с-MYC/8q24 and BCL2/18q21; 4 - with с-MYC/8q24 and BCL6/3q27) and one pt with triple translocations involving c-MYC/8q24, BCL2/18q21 and BCL6/3q27 genes and deletion of 17p13. 10 pts had morphological signs of transformation into aggressive lymphoma; 4 pts had FL 3A. There was 8 women and 6 men aged from 30 to 60 y. o. (median 47 y.o.). Lymph node with the highest FDG-accumulation according to PET-CT was chosen for biopsy and consequent immunohistochemistry and cytogenetics.
The majority of pts had high 12/14 and 2/14 - high-intermediate FLIPI score. All pts had advanced (III-IV) stage according to Ann-Arbor classification. 3 out of 14 pt had a history of low-grade FL (16-96 months) without c-MYC rearrangement in primary biopsy samples, in other 11 cases - anamnesis varied from 0,5 to 4,0 months. Lymphoma manifested by rapidly spread aggressive tumor with bulky disease: 2 pts had leukemic presentation of FL; 1 pt had FL cells in cerebrospinal fluid; 12/14 out of pts had several extranodal sites of involvement such as ovaries (2/8), kidneys or adrenals (6/14), paranasal sinuses (1/14); bones (3/14); soft tissues (4/14); lungs (3/14); stomach or intestine (4/14); spleen (4/14); liver (1/14). Ki-67 varied from 40 to 90%. An expression of c-MYC protein higher than 40% in 11/13 of FL pts. We didn’t revealed TP53 mutation within 7 out of 7 analyzed pts.
Results
None of pts had previous therapy. 4 pts were treated with R-CHOP-21. 3/4 (75%) out of pts died due to progressive disease (PD), 1/4 (25%) had partial remission (PR) after consequent therapy including obinutuzumab. 7 pts underwent modified BFM-protocol with Rituximab. 6/7 (86%) out of pts achieved complete remission (CR) after first-line treatment, 1 pt died due COVID-19 in PD status (14%). Autologous stem cell transplantation (auto-SCT) was performed in 4 out of 7 pts. 3 pts underwent R-DA-EPOCH. 1 pt achieved a CR after 6 courses, 1 pt - after second-line 2 R-DHAP; auto-SCT was performed for consolidation. 1 pt (33%) had PD after R-DA-EPOCH and another therapy. Rituximab supportive treatment was administrated only in 4 cases due to epidemiological situation. Median of observation was 9 months (1,0-59,5). We couldn’t study TP53 mutation status in pts with PD, but we observed PD in one case with deletion of 17p13.
Conclusion
For better diagnostics of FL transformation into HGBL DH we should perform biopsy of lymph node with the most active FDG accumulation according to PET-CT. We observed a higher rate of CR in this pts cohort when treated with intensive induction immunochemotherapy (modified BFM chemotherapy with rituximab) in comparison with R-CHOP/R-DA-EPOCH (86% vs 25% and 33%, respectively), and lower rate of primary resistance/PD (14% vs 75% and 33%). Our data needs consequent confirmation or consideration within metanalysis due to rare diagnostics of FL with double translocations of c-MYC and BCL2/BCL6. We should initiate a randomized study to estimate if auto-SCT had any benefits in comparison with a new immunotherapy modalities in FL transformed into HGBL DH.
Keyword(s): C-myc, Follicular lymphoma, High dose therapy, Transformation