R‐CHOP versus dose‐adjusted R‐EPOCH in frontline management of primary mediastinal B‐cell lymphoma: a multi‐centre analysis

Abstract

Primary mediastinal (thymic) large B-cell lymphoma (PMBCL) is an uncommon subtype of non-Hodgkin lymphoma (NHL) that presents with a mediastinal mass and has unique clinicopathological features. Historically, patients with PMBCL were treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy ± involved field radiation. Since a phase II trial, published in April 2013, demonstrated excellent results using dose-adjusted (DA) R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin), this treatment has gained popularity. We performed a retrospective, multicentre analysis of patients aged ≥18 years with PMBCL since January 2011. Patients were stratified by frontline regimen, R-CHOP versus DA-R-EPOCH. 132 patients were identified from 11 contributing centres (56 R-CHOP and 76 DA-R-EPOCH). The primary outcome was overall survival. Secondary outcomes included progression-free survival, complete response (CR) rate, and rates of treatment-related complications. Demographic characteristics were similar in both groups. DA-R-EPOCH use increased after April 2013 (79% vs. 45%, P < 0·001), and there was less radiation use after DA-R-EPOCH (13% vs. 59%, P < 0·001). While CR rates were higher with DA-R-EPOCH (84% vs. 70%, P = 0·046), these patients were more likely to experience treatment-related toxicities. At 2 years, 89% of R-CHOP patients and 91% of DA-R-EPOCH patients were alive. To our knowledge, this represents the largest series comparing outcomes of R-CHOP to DA-R-EPOCH for PMBCL.

What is the standard of care for primary mediastinal B cell lymphoma; R‐CHOP or DA‐EPOCH‐R? – Response to Melani et al

“…An ongoing randomized prospective clinical trial (NCT01599559) will help to answer this question and reduce the frequency of empiric radiation after R‐CHOP chemotherapy. At present, most centres continue to use consolidate radiation after R‐CHOP in PMBCL, as we have shown in our study (Shah et al , ).…”

“…We recently published our results from a multi‐center analysis evaluating two common frontline treatment regimens for patients with Primary Mediastinal B cell Lymphoma (PMBCL), DA‐R‐EPOCH (dose‐adjusted rituximab, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin) and R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). In our non‐randomized, retrospective analysis we found that while progression‐free survival (PFS) favoured DA‐R‐EPOCH (although not statistically significant), overall survival (OS) was similar at 2 years, 89% for R‐CHOP vs. 91% for DA‐R‐EPOCH (Shah et al , ). As a result, we were hesitant to make a strong recommendation for one specific regimen for the frontline management of PMBCL.…”

“…Lastly, although beyond the scope of our study, additional considerations when comparing regimens without an associated survival benefit include ease of patient administration and potential financial toxicity. Compared to R‐CHOP chemotherapy, DA‐R‐EPOCH mandates use of growth factor, requires 4 days of infusional chemotherapy, and is associated with more hospitalizations for both infusion of chemotherapy and treatment‐related complications (Shah et al , ). These issues need to be taken in context with the costs and time associated with mediastinal radiation, which is more often utilized after R‐CHOP.…”

Extranodal Diffuse Large B Cell Lymphoma: Molecular Features, Prognosis, and Risk of Central Nervous System Recurrence

“…It is characterized by PD-1 overexpression, constitutional JAK-STAT activation, and subtype-specific GEP [77]. Historically treated with RCHOP and consolidative RT, PMBCL has now shown excellent outcomes after DA-EPOCH-R chemotherapy alone, obviating the need for RT in the predominantly young, female population affected by this disease [78–80]. The low risk of CNS recurrence does not warrant prophylaxis.…”

What is the standard of care for primary mediastinal b‐cell lymphoma; R‐CHOP or DA‐EPOCH‐R?

“…We read with interest the report by Shah et al () on a retrospective, multi‐centre analysis comparing R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) to DA‐EPOCH‐R (dose‐adjusted rituximab, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin) as front‐line therapy for patients with primary mediastinal B‐cell lymphoma (PMBCL). The authors report that DA‐EPOCH‐R produced significantly greater complete remissions (CR) compared to R‐CHOP but similar 2‐year overall survivals, of 89% and 91%, respectively, suggesting equivalence.…”