Since the presentation on mediastinal lymphoma at the Pan Pacific Lymphoma Conference, Wyndham H. Wilson, MD, PhD, Chief of the Hematological Malignancies Therapeutics Section, Metabolism Branch, Cancer Research Center, of the National Cancer Institute in Bethesda, Maryland, offered The ASCO Post the following considerations:
The Vancouver R-CHOP results1 come from a retrospective analysis of patients from multiple centers that employed treatment guidelines. Furthermore, the outcome is presented as overall survival and over estimates the initial “curative potential” of R-CHOP, which is best determined by event-free survival. Importantly, the Vancouver group reported that among 35 patients who were positron-emission tomography (PET)-negative after R-CHOP and did not receive radiotherapy, 17% recurred.2 In contrast, among 51 patients from the National Cancer Institute and 16 patients from Stanford who received DA-EPOCH-R and no radiotherapy, only 3% recurred, irrespective of the PET scan results.3 Thus, the incidence of treatment failure after R-CHOP alone in PET-negative patients is high.
MINT Trial Reconsidered
In addition, Dr. Wilson noted that the retrospective analysis of the primary mediastinal B-cell lymphoma patients from the MINT trial4 only included patients with an International Prognostic Index score of 0 to 1. “Because patients with advanced stage disease were not included, where the outcome of R-CHOP is particularly poor, these results overestimate the outcome of R-CHOP and radiotherapy in [primary mediastinal B-cell lymphoma],” he said.
Dr. Wilson continued, “Multiple survivorship studies of radiotherapy in mediastinal Hodgkin lymphoma have shown a very high incidence of second and third cancers. The incidence of breast cancer is especially high, and [primary mediastinal B-cell lymphoma] is more common in young women. While newer radiation techniques may reduce secondary cancers, studies show that there is no safe dose of radiotherapy, and the changes in techniques do not reduce radiation dose in a major fashion.”
DA-EPOCH-R is the only immunotherapy treatment that has ever been prospectively studied, he pointed out. All of the other studies are either retrospective analyses and/or include radiotherapy.
Finally, Dr. Wilson noted that the cost of R-CHOP and radiotherapy is significantly greater than DA-EPOCH-R and extends treatment for weeks.
“Based on these findings,” he commented, “I think until proven otherwise, DA-EPOCH-R should be considered the standard for [primary mediastinal B-cell lymphoma].”
He added that the data presented on gray zone lymphoma at the Pan Pacific meeting are older and based on an abstract. “Our full series is now published online with updated and improved outcomes.”5 ■
Disclosure: Dr. Wilson reported no potential conflicts of interest.
References
1. Savage KJ, Yenson PR, Shenkier T, et al: The outcome of primary mediastinal large B-cell lymphoma (PMBCL) in the R-CHOP treatment era. 2012 American Society of Hematology Annual Meeting. Abstract 303. Presented December 10, 2012.
2. Savage KJ, Yenson PR, Shenkier T, et al: The outcome of primary mediastinal large B-cell lymphoma (PMBCL) in the R-CHOP treatment era. 2012 American Society of Hematology Annual Meeting. Abstract 303. Presented December 10, 2012.
3. Dunleavy K, Pattaluga S, Maeda LS, et al: Dose-adjusted EPOCH-rituximab therapy in primary mediastinal B-cell lymphoma. N Engl J Med 368:1408-1416, 2013.
4. Pfreundschuh M, Trümper L, Osterborg A, et al: CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: A randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol 7:379-391, 2006.
5. Wilson WH, Pittaluga S, Nicolae A, et al: A prospective study of mediastinal gray zone lymphoma. Blood. July 14, 2014 (early release online).
