Survival of Patients with Primary Mediastinal B-Cell Lymphoma Treated By Immunochemotherapy with or without Radiotherapy

Introduction: Primary mediastinal B-cell lymphoma (PMBL) is B-non-Hodgkin lymphoma subtype with unique clinical and biological characteristics mostly affecting younger patients. The current treatment standard is based on combination of rituximab and anthracycline based chemotherapy (R-CHT), either standard (R-CHOP) or intensified (DA-EPOCH-R). Radiotherapy (RT) consolidation has been standard of care for a long time, but its role is currently unclear, especially in the context of PET/CT guided therapy and long term toxicity prevention considering young patient population (Hayden at al.2020, Giulino-Roth 2018). In this analysis we evaluate the survival benefit of RT consolidation in patients with PMBL achieving PET negative (PET-neg) response after R-CHT.

Methods: Patients with confirmed diagnosis of PMBL observed in NiHiL project (Gov Trial No: NCT03199066) were analysed. All patients were treated by R-CHT; PET/CT was performed at the end of the immunochemotherapy. The treatment response was evaluated according to Cheson 2007 criteria. Only patients achieving PET negativity were included in primary analysis.

Results: The study included 230 patients out of whom 133 (57.8%) were women. Median age was 37 years (range 19-79); localised stage (I-II) was observed in 165 patients (71.7%) and low or low-intermed IPI in 189 patients (82.2%). The diagnosis was confirmed by central pathologist in all cases. Patients were treated by R-CHT, mostly R-CHOP (52.2%) and R-CHOEP-like (25.2%; i.e. R-CHOEP or DA-EPOCH-R); other intensive regimens, incl. platinum were used in 19.6% of patients; 48 patients (20.8%) received ASCT as part of first line induction. PET/CT was performed at the end of R-CHT (including ASCT); 174 patients (75.7%) achieved PET-neg remission at the end of the immunochemotherapy, 56 (24.3%) were PET positive (PET-pos). After reaching PET negativity, radiotherapy was performed in 68 patients (39.1%) with median dose of 36Gy (range 20-42Gy); 106 patients were not consolidated by RT and observed (OBS). There was higher incidence of bulky disease and B-symptoms in RT group (57% vs 47% and 57% vs 48% resp.) without reaching statistical significance. Median follow up was 5.9 years. OS and PFS probability at 6y were 90.5% and 83.6% resp. for the whole cohort. RT consolidation in PET-negative subgroup led to a significant improvement (p=0.039) in PFS at 6y with 95% (n=68) vs 85.3% in OBS group (n=106). This was, however, not transformed into the OS difference (94.5% vs 92.1% probability at 6y for RT vs OBS; HR 1.64, CI95% 0.52-5.8), figure 1. In subgroup of patients treated by R-CHOP, there was an insignificant trend for better PFS probability in RT group (HR 2.41, 95%CI 0.71-6.92, p=0.17). This was not reflected in any OS difference. The outcome of patients who reached PET negativity by R-CHOEP was the same regardless of the radiotherapy use.

Conclusion: Our analysis of retrospectively recorded patients shows that skipping RT in PET-neg PMBL patients at the end of immunochemotherapy does not hamper overall survival. There was borderline improvement of PFS. The patient cohorts with different chemotherapy regimens were not big enough to analyse the RT significance. However, data observed in patient subpopulation treated by CHOEP-like regimen confirm already published observations (Dunleavy et al. 2013) concluding possible RT oblivion after intensified immunochemotherapy. Therefore, the choice between radiotherapy consolidation vs observation in PET negative patients should be discussed with the patient especially when less intensive regimen (R-CHOP) is used.

Acknowledgement: This work was supported by Cooperatio Program - research area Oncology and Hematology and by research grant NU21-03-00411

Figure 1. Survival analysis of patients reaching PET negative remission after chemotherapy (n=174) shows improvement in progression free survival (PFS) for patients consolidated with radiotherapy (RT), however without reflection in overall survival (OS).

Polgarova:Kyowa Kirin: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Roche: Honoraria. Janíková:Roche: Consultancy; Takeda: Consultancy; Gilead: Consultancy; Janssen: Consultancy. Belada:Reddy´s: Research Funding; Pharmacyclics: Research Funding; MorphoSys AG: Consultancy, Research Funding; Genmab: Research Funding; Janssen-Cilag: Consultancy, Research Funding; Takeda: Consultancy, Other: travel expenses, Research Funding; Roche: Consultancy, Other: travel expenses, Research Funding; Gilead: Consultancy, Other: travel expenses. Prochazka:Novartis: Speakers Bureau; Takeda: Speakers Bureau; Hoffmann-La Roche: Speakers Bureau. Ďuraš:Celgene: Consultancy; Roche: Consultancy; Bristol Myers squibb: Consultancy; Takeda: Consultancy. Zogala:Pfizer: Consultancy; Novartis: Consultancy; Biogene: Consultancy; Astellas: Consultancy. Trneny:MorphoSys: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead Sciences: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Zentiva: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding.