What is the role of consolidation therapy in the treatment of primary mediastinal B-cell lymphoma (PMBCL)?

Updated: Sep 14, 2019
  • Author: Sonali M Smith, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Answer

Prior to the wide use and adaptability to PET scans, most patients underwent consolidative RT or high-dose chemotherapy and autologous hematopoietic stem cell transplantation (auto-HSCT) after completion of systemic therapy. While this approach continues to be commonly used, it has become increasingly controversial, especially in patients who attain complete PET scan negativity upon completion of systemic chemoimmunotherapy.

Several reports have suggested inferior survival in patients with DLBCL who have residual PET scan positivity at the end of chemotherapy and other studies have shown that patients who have a positive interim PET scan (after 2-4 cycles of therapy) predict higher risk of subsequent relapse. [30, 31, 32] However, treatment decisions in patients who remain PET positive after completion of systemic therapy should never be based solely on the PET scan interpretation. Moskowitz et al showed in a large phase II study that the majority of DLBCL patients who remained PET positive had no residual disease when diagnostic biopsies were performed. [33] In that report, 30% of the 98 enrolled patients had PMBCL.

Whether RT should be delivered to all patients with PMBCL regardless of PET scan results or whether this approach should be individualized based on PET and/or other clinical or prognostic features remain unknown.

Savage et al reported on the British Columbia experience. [34] CHOP-R followed by consolidative RT was the adapted approach to all PMBCL patients diagnosed and treated from 2001–2005. After 2005, PET scanning was used to guide RT following 6 cycles of CHOP-R. To that end, if the PET scan was negative, patients were observed and if the PET scan was positive, consolidative RT was given. In total, 176 patients were identified: 96 received CHOP-R and 80 received CHOP. For the CHOP-R treated patients, 46 were treated in the “RT era” with 80% receiving RT; 50 were treated in the “PET era”; 38% received RT. Comparing between eras, no overall survival was suggested by adding RT. Further, when PET-positive patients received RT consolidation, no significant difference in outcome was observed between PET-positive and PET-negative patients, suggesting that some patients can avoid undergoing RT when PET is used to guide therapy.

In an attempt to eliminate RT, Dunleavy et al recently reported a phase II trial on 51 patients who were treated with DA-EPOCH-R and showed excellent results. With a median follow-up of 5 years, event-free survival was 93% and overall survival was 97%. For patients who had a PET on this study, the negative predictive value was 100%, while the positive predictive value was 17%. This finding is in line with the data from Moskowitz et al (see above), for which patients have false-positive PET scans after completion of therapy, and underscores the importance of not making therapeutic decisions based on PET findings only. In all, only 2 patients (4%) underwent RT when DA-EPOCH-R was used.

The use of consolidative auto-HSCT in patients with PMBCL stems from the effectiveness of this approach in patients with relapsed DLBCL. [35] Residual disease radiographically was hypothesized to represent persistent lymphoma and patients underwent the aggressive salvage therapy as PET scans were not available then. With the advent of PET and continued standardization of its interpretation, The European Society for Medical Oncology (ESMO) guidelines recommend against routine use of auto-HSCT as a primary consolidative approach. [36] Whether patients who have residual disease that is established histologically should undergo RT or auto-HSCT is unknown. Enrolling these patients in clinical trials is an option, if available. Outside of clinical trials, the decision needs to be individualized and would factor prognostic features, morbid conditions, and patients' wishes. 


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