Contributions
Abstract: EP781
Type: E-Poster Presentation
Session title: Hodgkin lymphoma - Clinical
Background
PD-1 inhibitors represent an effective option in the treatment of relapsed and refractory classical Hodgkin lymphoma (r/r cHL). The chromosomal alterations in 9p24.1 (PD-L1 and PD-L2) locus were shown to be a characteristic feature of malignant Reed-Sternberg (RS) cells, and considered as a potential predictive marker of immunotherapy efficiency in the limited number of reports.
Aims
The aim of the current study was to investigate the prevalence and the type of 9p24.1 alterations in severely the pretreated population of r/r cHL patients receiving nivolumab (nivo) during Russian named patient program, as well as to assess their influence on the efficiency of immunotherapy
Methods
This retrospective analysis included 46 patients with r/r cHL who were treated with nivo (26 female and 20 male). The median age was 30 (14-64). The histological types of cHL in this cohort were nodular sclerosis in 84,8% (n=39), mixed cellularity 8,7% (4), lymphocyte rich 4,3% (2), and lymphocyte depleted in 2,2% (1). An advanced disease at initial diagnosis was in 65,2 % (n= 30) of patients; 56,5% (n=26) of patients had primary resistant disease. The median number of previous lines of therapy was 5 (2-10).
In 7 patients, the tumor biopsy was performed at the disease progression after immunotherapy with subsequent 9p24.1 locus analysis. Determination of the type of alteration in the biopsies was carried out according to the protocol presented in the previously published studies (Roemer MG, et.al. 2016).
Results
The alterations of the PD-L1 and PD-L2 loci were observed in all analyzed tumor specimens before and after nivo treatment. The type of alteration observed before immunotherapy was polysomy in 9% (n = 4), copy gain - in 69% (n = 32), amplification - in 22% (n = 10) of cases. The comparison of 9p24.1 alteration structure before and after immunotherapy showed an increase in the number of cases with 9p24.1 locus amplification (1/7 before vs. 4/7 after, p=0,14).
The analysis of the association of 9p24.1 alterations with the clinical outcomes was performed. There was a significant difference in progression-free survival among patients according to alteration type (p = 0.02): for 9p24.1 amplification, a 3-year PFS was 20% (95% CI 3.1- 47%) with median of 20.6 months (95% CI 6.6-35.6), for copy gain a 3-year PFS was 34% (95% CI 18-50%) with median PFS 23.8 months (95% CI 6.6- 35.6) and for polysomy, a 3-year PFS was 0% with a median PFS 7.2 months (95% CI 4.3-NE). However, the statistically significant influence of alteration type on best overall response was not observed (p = 0.2).
There was no significant dependences between alteration type and analyzed clinical factors, including initial disease stage (p = 0.86), the initial presence of B-symptoms (p = 0.78), and the primary refractory disease (p = 0.98). Despite the limited number of patients, a significant association (p = 0.03) of chromosomal alterations with the histological type of cHL was observed in the analyzed population: in all cases of 9p24.1 amplification, the nodular sclerosis type of cHL was confirmed during the histological investigation.
Conclusion
The polysomy of 9p24.1 may be considered as a negative prognostic factor regarding progression-free survival in a limited population of patients. The dynamics of 9p24.1 locus alterations before and after nivolumab therapy, as well as their association with the histological type of classical Hodgkin lymphoma were described.
Keyword(s): FISH, Hodgkin's lymphoma, Immune therapy, Prognostic factor
Abstract: EP781
Type: E-Poster Presentation
Session title: Hodgkin lymphoma - Clinical
Background
PD-1 inhibitors represent an effective option in the treatment of relapsed and refractory classical Hodgkin lymphoma (r/r cHL). The chromosomal alterations in 9p24.1 (PD-L1 and PD-L2) locus were shown to be a characteristic feature of malignant Reed-Sternberg (RS) cells, and considered as a potential predictive marker of immunotherapy efficiency in the limited number of reports.
Aims
The aim of the current study was to investigate the prevalence and the type of 9p24.1 alterations in severely the pretreated population of r/r cHL patients receiving nivolumab (nivo) during Russian named patient program, as well as to assess their influence on the efficiency of immunotherapy
Methods
This retrospective analysis included 46 patients with r/r cHL who were treated with nivo (26 female and 20 male). The median age was 30 (14-64). The histological types of cHL in this cohort were nodular sclerosis in 84,8% (n=39), mixed cellularity 8,7% (4), lymphocyte rich 4,3% (2), and lymphocyte depleted in 2,2% (1). An advanced disease at initial diagnosis was in 65,2 % (n= 30) of patients; 56,5% (n=26) of patients had primary resistant disease. The median number of previous lines of therapy was 5 (2-10).
In 7 patients, the tumor biopsy was performed at the disease progression after immunotherapy with subsequent 9p24.1 locus analysis. Determination of the type of alteration in the biopsies was carried out according to the protocol presented in the previously published studies (Roemer MG, et.al. 2016).
Results
The alterations of the PD-L1 and PD-L2 loci were observed in all analyzed tumor specimens before and after nivo treatment. The type of alteration observed before immunotherapy was polysomy in 9% (n = 4), copy gain - in 69% (n = 32), amplification - in 22% (n = 10) of cases. The comparison of 9p24.1 alteration structure before and after immunotherapy showed an increase in the number of cases with 9p24.1 locus amplification (1/7 before vs. 4/7 after, p=0,14).
The analysis of the association of 9p24.1 alterations with the clinical outcomes was performed. There was a significant difference in progression-free survival among patients according to alteration type (p = 0.02): for 9p24.1 amplification, a 3-year PFS was 20% (95% CI 3.1- 47%) with median of 20.6 months (95% CI 6.6-35.6), for copy gain a 3-year PFS was 34% (95% CI 18-50%) with median PFS 23.8 months (95% CI 6.6- 35.6) and for polysomy, a 3-year PFS was 0% with a median PFS 7.2 months (95% CI 4.3-NE). However, the statistically significant influence of alteration type on best overall response was not observed (p = 0.2).
There was no significant dependences between alteration type and analyzed clinical factors, including initial disease stage (p = 0.86), the initial presence of B-symptoms (p = 0.78), and the primary refractory disease (p = 0.98). Despite the limited number of patients, a significant association (p = 0.03) of chromosomal alterations with the histological type of cHL was observed in the analyzed population: in all cases of 9p24.1 amplification, the nodular sclerosis type of cHL was confirmed during the histological investigation.
Conclusion
The polysomy of 9p24.1 may be considered as a negative prognostic factor regarding progression-free survival in a limited population of patients. The dynamics of 9p24.1 locus alterations before and after nivolumab therapy, as well as their association with the histological type of classical Hodgkin lymphoma were described.
Keyword(s): FISH, Hodgkin's lymphoma, Immune therapy, Prognostic factor