Outcome of primary mediastinal large B-cell lymphoma using R-CHOP: impact of a PET-adapted approach

Abstract

Cure rates for primary mediastinal large B-cell lymphoma (PMBCL) have improved with the integration of rituximab. However, the type of primary therapy and role of radiotherapy (RT) remains ill-defined. Herein, we evaluated the outcome of PMBCL primarily treated with R-CHOP and the impact of an end-of-treatment (EOT) FDG-PET scan to guide consolidative RT. Patients ≥18 years of age with PMBCL treated with curative intent R-chemotherapy were identified. Prior to 2005, patients were recommended to receive R-CHOP +RT (RT era). Beginning in 2005, EOT PET was used to guide RT and only those with a PET-positive scan received RT (PET era). In total, 159 patients were identified, 94% were treated with R-CHOP and 44% received RT - 78% in RT era, 28% in PET era. The 5-year time to progression (TTP) and OS for the entire cohort were 80% and 89%, respectively, similar across treatment eras. Overall, 10% had refractory disease. In total, 113 patients had an EOT PET scan: 63% negative and 37% positive with a 5-year TTP of 90% vs 71% and 5-year OS of 97% vs 88%, respectively. For those with Deauville (D) scored PET scans (n=103), the 5-year TTP for PET-negative cases by Deauville criteria (D1-D3,DX) was 91%, with inferior outcomes for D5 vs D4 (5-year TTP 33% vs 87%, p=0.0002). Outcomes for R-CHOP treated PMBCL patients treated with R-CHOP are favorable and use of a PET-adapted approach reduces RT in the majority of patients. A small proportion have refractory disease and may benefit from an alternate treatment.

Identification of Very Low-Risk Subgroups of Patients with Primary Mediastinal Large B-Cell Lymphoma Treated with R-CHOP

“…These considerations support the applicability of our risk models in everyday clinical practice. The decision to irradiate or not after induction therapy is currently based on the initial chemotherapy regimen and the final PET result [6,[31][32][33][34][35][36]60,67,68], whereas the impact of baseline prognostic markers on this decision remains to be further delineated. Obviously, the latter issue may not be applicable if patients with one or two risk factors are selected for R-da-EPOCH treatment, where RT is typically omitted.…”

Primary Mediastinal B-Cell Lymphoma: Novel Precision Therapies and Future Directions

“…Moreover, the difference in 5-year TTP prognosis between Deauville score 4 and Deauville score 5, was 33% and 87%, respectively, P = 0.0002). This study clearly demonstrated that PMBCL patients could achieve considerable curative effects through the R-CHOP regimen, and using PET-CT adaptive therapy could reduce exposure to RT for most PET-negative patients ( 53 ). A limited number of patients Deauville score 4 in IELSG-26 study also achieved satisfactory outcomes ( 46 ).…”

“…A model that combines the evaluation of baseline TLG and the Deauville score at the end of treatment could identify patients with a high risk of progression ( 56 , 57 ). Therefore, this prognostic model may screen high-risk patients for more intensive treatment or even combine with new targeted treatments such as pembrolizumab ( 53 ). In the future, baseline quantitative PET-CT may be used to provide an earlier definition of a risk-adapted therapeutic strategy in PMBCL through this new tumor metabolizing biomarker.…”

Real-world data on treatment and outcomes of patients with primary mediastinal large B-cell lymphoma: a Swedish lymphoma register study

“…Primary mediastinal large B-cell lymphoma (PMBL) is an aggressive lymphoma subtype that predominantly affects women in their 3rd–4th decade. Due to the rarity of PMBL, optimal treatment, including choice of chemotherapy regimen and necessity of radiotherapy (RT), is not established 1 – 3 .…”

“…This is in line with previous studies which show excellent results with various regimens without RT 1 . In addition, in studies where PET-guided RT has been applied, PET-negative patients have safely been managed without RT 3 , 8 . Further, as false-positive PET scans are common, accumulating evidence suggests that PET-positive patients can be followed with serial PET scans and that biopsy is required to confirm persistent lymphoma, before considering additional therapy 9 .…”