ESMO 2016 | Multidisciplinary Cases Session: Therapy regimens for treatment of patients with Central Nervous System (CNS) relapses and Secondary CNS Lymphoma

Andrés J.M. Ferreri from the IRCCS San Raffaele Scientific Institute presented a multidisciplinary session focused on studies on patients with Extranodal Lymphomas experiencing Central Nervous System (CNS) relapses and Secondary CNS Lymphoma (SCNSL) at the ESMO Congress 2016, at Copenhagen, Denmark.

Andrés J.M. Ferreri started his presentation by focusing on a type of Extranodal Lymphoma, Primary Testicular Lymphoma (PTL), one of the most common testicular neoplasm that usually affects men aged 60 and over.

• He showed sections of PTL cells, which has an immunophenotype similar to Diffuse Large B-Cell Lymphoma (DLBCL). He then focused on therapeutic strategies for PTL patients. 

Andrés J.M. Ferreri presented a retrospective study published by Zucca et al. on patients with Primary Diffuse Large Cell Lymphoma of the testis with an aim to better define the specific clinical features, response to therapy and patterns of failure.

• 373 patients (median age = 66 years) with different stages of PTL were investigated for their response to therapy. The patients in this study were either enrolled onto prospective studies or were consecutively treated patients. The median Overall Survival (OS) was 5 years and 5- and 10- year OS were 48% and 27%, respectively. The 5- and 10- year Cause Specific Survival (CSS) rates were 55% and 43%, respectively. The median Progression Free Survival (PFS) was 4 years and 5- and 10- years PFS were 48% and 33%, respectively.  

• Andrés J.M. Ferreri queried that some patients in this study experienced therapeutic challenges including risk of extranodal relapses, contralateral testicular failure and risk of CNS recurrence. He presented more data from the retrospective study by Zucca et al.
• In patients not receiving radiotherapy, there was a risk of contralateral testicular failure (15% at 3 years, 42% at 15 years). The risk of continuous CNS failure was 19% at 5 years and 34% at 10 years.

Then, Andrés J.M. Ferreri noted that relapses at extranodal sites, especially the CNS and the contralateral testis, are the most therapeutic challenges in patients with Extranodal Lymphoma and then proposed a therapy regimen for these patients. He suggested that the best therapeutic option for these patients would be R-CHOP (rituximab added to cyclophosphamide, doxorubicin, vincristine and prednisone) plus CNS prophylaxis and testis radiotherapy.

• To illustrate this, he presented data from a prospective phase II trial in patients with Primary Testicular Diffuse Large B-Cell Lymphoma (PTDLBL) published by Vitolo et al. 53 patients were treated with R-CHOP, CNS prophylaxis (intrathecal methotrexate [MTX]) and radiotherapy to the contralateral testis. 

• From the study, the 5-year OS was 85% and the incidence of contralateral testis relapses have been eliminated with the treatment regimen used in this study. The 5-year cumulative incidence of CNS relapse, taking into account the competitive risk of death, was 6%, suggesting this therapeutic strategy is feasible and well tolerated by patients. Although the CNS relapses decreased, it was not completely eliminated. Andrés J.M. Ferreri suggested that new therapeutic strategies to reduce the occurrence of CNS relapses in patients with Lymphoma should be considered.   

To illustrate this, he presented recent data from an abstract submitted and presented at the ESMO Congress, 2016.

• 242 Patients with DLBCL treated with first line R-CHOP or other radiotherapy agents were considered for this trial. Patients with high risk of CNS recurrence were given High-Dose methotrexate (HDMTX). The 3-year PFS (78%) in patients with high-risk of CNS relapse given HDMTX was significantly higher compared to patients that did not receive this treatment (43%). The 3-year OS in patients with high-risk of CNS relapse given HDMTX (81%) was significantly higher compared to patients that did not receive this treatment (40%). These results indicate that the addition of HDMTX is effective in DLBCL patients with increased risk of CNS recurrence. 

Andrés J.M. Ferreri noted that patients with aggressive Lymphomas are at risk of secondary CNS dissemination. Therapy for patients with SCNSL is limited and more intensive strategies require verification. Following this, he presented a phase II trial designed for the treatment of patients (aged 18–70 years) with aggressive CD20+ B-cell Lymphoma and secondary CNS involvement at diagnosis or relapse.

• Patients were treated with of HD-MTX and cytarabine combined with rituximab and intrathecal liposomal cytarabine followed by R-HDS (cyclophosphamide, cytarabine and etoposide) supported by Autologous Stem-Cell Transplantation (ASCT). The primary endpoint was 2-year Event Free Survival (EFS). ​

• The data obtained from the prospective trial show that at a median follow up of 48 months, 5-year EFS was 40% for the whole series of patients. EFS for patients that received transplantation was 63%. OS of patients that received transplantation was 68% compared to the whole series, which was 41%. 

• Andrés J.M. Ferreri stated that the results of this prospective trial demonstrated that the treatment strategy is feasible in patients older than 65 years, and also in patients with poor prognosis. 

Andrés J.M. Ferreri concluded his talk at the multidisciplinary cases session at ESMO Congress 2016 by suggesting that the best treatment regimens for patients with SCNSL consist of a combination of high-dose chemotherapy supported by ASCT.