Contributions
Abstract: PB1795
Type: Publication Only
Background
Presence of secondary c-MYC rearrangement (c-MYC-R) in patients with follicular lymphoma (FL) can predispose to a histologic transformation of FL and aggressive clinical course of the disease. That could be explained by the fact that finding of a secondary chromosomal break of c-MYC along with inactivation of tumour suppressor genes (TP53, CDKN2A/B, B2M) is one of predisposing factors to FL transformation Therapeutic approaches to treatment of FL with с-MYC-R have not yet been clearly defined.
Aims
To describe clinical characteristics and treatment efficacy of FL patients presenting with c-MYC-R.
Methods
From 2015 to 2018 in National Scientific Center, were diagnosed 8 cases of FL with c-MYC-R (5 males and 3 females). Median age was 34,5 years (from 30 to 57). Median of follow-up was 8,8 months (from 5 to 25,6). Taking into account that in the majority of cases, except of c-MYC locus translocation, a tumour was represented by FL 3B, transformed FL or blastoid variant of FL, we had an intention to treat with R-(DA)-EPOCH, what was more intense than commonly used treatment approaches of FL. In case of incomplete antitumor response, autologous stem cell transplantation (auto-SCT) was planned.
Results
7 out of 8 pts had a widespread tumour, ECOG≥2, 6 – increased LDH activity, multiple extranodal involvements. In 6 cases tumour manifested with FL grade 3B; in 3 of them were revealed signs of large-cell transformation; in 2 – with FL grade 3A with blastoid morphological features. In 4 out of 4 cases which had been stained with c-MYC, c-MYC expression was≥40%. 3 cases (FL grade 3B with foci of DLBCL) were BCL2-negative (<50%). Median of Ki-67 was 80% (40-85%). All 8 cases were positive for c-MYC-R. Pts, who manifested with FL grade 3A, had c-MYC and BCL2 rearrangements (c-MYC/BCL2-R), with FL grade 3B - c-MYC/BCL6-R in 3 cases, in case of FL transformation into DLBCL were revealed c-MYC/BCL2/BCL6-R. This distribution highlights common pathogenesis between FL3B and DLBCL. G-banding was performed in 7 pts and revealed complex karyotype abnormalities. Five out of 8 of pts with FL underwent R-(DA)-EPOCH, 3 - R-CHOP-21. In a group of 5 pts after R-DA-EPOCH, 2 pts had complete remission (CR) (one case of FL 3A with c-MYC/BCL2-R, another case of FL 3B with solely c-MYC-R), 3 pts needed second-line treatment (R-DHAP) due to progressive disease (PD) (2 cases of FL 3B with c-MYC/BCL6-R) or partial remission (PR) (1 case of FL 3A with c-MYC/BCL2-R). The last one achieved CR after 2 R-DHAP, later auto-SCT was performed. Another pt had stable disease (SD), auto-SCT was planned. Third one died due to progressive disease (PD). Three pts underwent R-CHOP: one case of FL 3B with c-MYC/BCL6-R had CR after 5 R-CHOP, but soon died due to bleeding of unknown source. Two another pts had PD after R-CHOP (one pt with triple-hit lymphoma died due to PD, another pt with FL 3B and solely c-MYC-R is alive with signs of disease). Thus, from 8 pts only 5 are alive, 2 of them with disease. Auto-SCT wasn’t performed in spite of intention in two cases due to fast lymphoma progression.
Conclusion
FL with c-MYC rearrangement especially in combination with translocations involving BCL2 and/or BCL6 represents an aggressive tumour which requires more intensive approach than R-CHOP. Patients with FL who didn’t achieve CR at the first line of treatment might have benefited from high dose therapy following auto-SCT. Otherwise, new treatment approaches are needed (CAR T-cells, clinical trials).
Session topic: 21. Aggressive Non-Hodgkin lymphoma - Clinical
Keyword(s): c-Myc, Follicular lymphoma, Transformation, Autologous hematopoietic stem cell transplantation
Abstract: PB1795
Type: Publication Only
Background
Presence of secondary c-MYC rearrangement (c-MYC-R) in patients with follicular lymphoma (FL) can predispose to a histologic transformation of FL and aggressive clinical course of the disease. That could be explained by the fact that finding of a secondary chromosomal break of c-MYC along with inactivation of tumour suppressor genes (TP53, CDKN2A/B, B2M) is one of predisposing factors to FL transformation Therapeutic approaches to treatment of FL with с-MYC-R have not yet been clearly defined.
Aims
To describe clinical characteristics and treatment efficacy of FL patients presenting with c-MYC-R.
Methods
From 2015 to 2018 in National Scientific Center, were diagnosed 8 cases of FL with c-MYC-R (5 males and 3 females). Median age was 34,5 years (from 30 to 57). Median of follow-up was 8,8 months (from 5 to 25,6). Taking into account that in the majority of cases, except of c-MYC locus translocation, a tumour was represented by FL 3B, transformed FL or blastoid variant of FL, we had an intention to treat with R-(DA)-EPOCH, what was more intense than commonly used treatment approaches of FL. In case of incomplete antitumor response, autologous stem cell transplantation (auto-SCT) was planned.
Results
7 out of 8 pts had a widespread tumour, ECOG≥2, 6 – increased LDH activity, multiple extranodal involvements. In 6 cases tumour manifested with FL grade 3B; in 3 of them were revealed signs of large-cell transformation; in 2 – with FL grade 3A with blastoid morphological features. In 4 out of 4 cases which had been stained with c-MYC, c-MYC expression was≥40%. 3 cases (FL grade 3B with foci of DLBCL) were BCL2-negative (<50%). Median of Ki-67 was 80% (40-85%). All 8 cases were positive for c-MYC-R. Pts, who manifested with FL grade 3A, had c-MYC and BCL2 rearrangements (c-MYC/BCL2-R), with FL grade 3B - c-MYC/BCL6-R in 3 cases, in case of FL transformation into DLBCL were revealed c-MYC/BCL2/BCL6-R. This distribution highlights common pathogenesis between FL3B and DLBCL. G-banding was performed in 7 pts and revealed complex karyotype abnormalities. Five out of 8 of pts with FL underwent R-(DA)-EPOCH, 3 - R-CHOP-21. In a group of 5 pts after R-DA-EPOCH, 2 pts had complete remission (CR) (one case of FL 3A with c-MYC/BCL2-R, another case of FL 3B with solely c-MYC-R), 3 pts needed second-line treatment (R-DHAP) due to progressive disease (PD) (2 cases of FL 3B with c-MYC/BCL6-R) or partial remission (PR) (1 case of FL 3A with c-MYC/BCL2-R). The last one achieved CR after 2 R-DHAP, later auto-SCT was performed. Another pt had stable disease (SD), auto-SCT was planned. Third one died due to progressive disease (PD). Three pts underwent R-CHOP: one case of FL 3B with c-MYC/BCL6-R had CR after 5 R-CHOP, but soon died due to bleeding of unknown source. Two another pts had PD after R-CHOP (one pt with triple-hit lymphoma died due to PD, another pt with FL 3B and solely c-MYC-R is alive with signs of disease). Thus, from 8 pts only 5 are alive, 2 of them with disease. Auto-SCT wasn’t performed in spite of intention in two cases due to fast lymphoma progression.
Conclusion
FL with c-MYC rearrangement especially in combination with translocations involving BCL2 and/or BCL6 represents an aggressive tumour which requires more intensive approach than R-CHOP. Patients with FL who didn’t achieve CR at the first line of treatment might have benefited from high dose therapy following auto-SCT. Otherwise, new treatment approaches are needed (CAR T-cells, clinical trials).
Session topic: 21. Aggressive Non-Hodgkin lymphoma - Clinical
Keyword(s): c-Myc, Follicular lymphoma, Transformation, Autologous hematopoietic stem cell transplantation