Treatment of primary mediastinal B-cell lymphoma with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone is associated with a high rate of primary refractory disease

Abstract

The optimal therapy for primary mediastinal B-cell lymphoma is a subject of ongoing debate, with no accepted standard of care. We performed a retrospective analysis of 63 patients in the modern era treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), with or without radiation. Median age was 37 years (range 20-82). Eighty percent had limited stage disease and 71% were bulky. By age-adjusted International Prognostic Index (IPI), 15% were low-risk, 52% low-intermediate, 27% high-intermediate and 6% high-risk. Some 77% of responding patients received consolidative radiotherapy. Overall and complete response rates were 79% and 71%. Primary induction failure occurred in 13 (21%) patients. Five-year PFS and OS were 68% and 79%, respectively. Adverse prognostic features included increased IPI, advanced stage, advanced age and multiple extranodal sites. These data demonstrate an unacceptably high rate of primary refractory disease on R-CHOP, particularly among patients with high-risk features. Novel treatment approaches are needed that reduce primary refractory disease and reliance on mediastinal radiation in young people.

Primary mediastinal B-cell lymphoma and mediastinal gray zone lymphoma: do they require a unique therapeutic approach?

“…27 Although R-CHOP followed by radiation has been effective in lowrisk patients, it appears to be insufficient therapy for patients with high-risk disease and is associated with a high rate of primary refractory disease. 37 On the basis of its promising efficacy in a National Cancer Institute study, we recommend DA-EPOCH-R without radiation while confirmatory studies are in progress. After this regimen without radiation, end-of-therapy FDG-PET has an excellent negative predictive value but low positive predictive value, so end-of-therapypositive FDG-PETs need to be interpreted cautiously with regard to decisions about consolidation radiation.…”

“…A recent retrospective analysis of R-CHOP (followed by mediastinal radiation in 77% of responders) in 58 patients with PMBL that included all IPI groups showed a high rate of primary induction failures (21%) and an overall PFS of 68% at 5 years. 37 Another retrospective analysis from the Memorial Sloan Kettering Cancer Center group evaluated R-CHOP followed by ifosfamide, cyclophosphamide, and etoposide without radiation and reported a PFS of 78% at 3 years. 38 A British Columbia study that looked at the outcome of PMBL in the rituximab era reported on a subset of patients in whom an FDG-PET-guided RT approach (ie, FDG-PET-negative cases were not radiated) was used.…”

Role of radiotherapy in the treatment of primary mediastinal large B-cell lymphoma

“…A study on 37 PMLBCL patients found that ~50% of PMBCL patients showed residual disease on PET scan following rituximab plus chemotherapy (24). A recent retrospective study on 63 PMLBCL patients treated with RCHOP showed that primary induction failure occurred in 13 (20.6%) patients (25).…”

Precision Treatment of Distinct Molecular Subtypes of Diffuse Large B-cell Lymphoma: Ascribing Treatment Based on the Molecular Phenotype

“…Patients who received rituximab had a superior 3-year event-free survival (78% vs. 52% in the chemotherapy arm alone)-because of small numbers, an OS difference was not appreciated. Most patients in this analysis received preplanned mediastinal radiation which improved remission rates (93,94). It is important to consider that the MInT study was confined to patients with a low IPI score ( 1) and therefore did not include the entire spectrum of patients with this disease.…”

“…One of these retrospectively evaluated 58 patients of all IPI groups treated with R-CHOP (followed by mediastinal radiation in 77% of responders; ref. 94). There was a high rate of primary induction failures (21%), and the overall PFS at 5 years was 68% (94).…”