Treatment of primary mediastinal large B cell lymphoma with an alternating chemotherapy regimen based on high-dose methotrexate

Abstract

International audiencePrimary mediastinal large B cell lymphomas (MLCL) differ from other diffuse large cell lymphomas, leading to a description as a separate entity in the current World Health Organization classification. Dose intensification improves long-term results, but no standard therapy has been established so far. We investigated the use of a high-dose methotrexate-based alternating chemotherapy regimen (B-ALL protocol of the German ALL study group) followed by consolidative mediastinal radiotherapy first as a single-center trial, then later as a prospective multicenter trial in 44 patients with a median age of 33 years. Response rates exceeded 90% with an overall survival rate of 80% in the single-center group (8.6 years median follow-up) and 82% in the multicenter group (2.5 years follow-up).Short-term toxicity was manageable, but required hospitalization: the rates of grade 3 or 4 toxicity were 20% (for mucositis), 42% (for neutropenia), 29% (for thrombocytopenia), and 9% (for neutropenic fever). No relapse occurred more than 2 years after diagnosis and initiation of treatment, but unfortunately, no patient with overt progression or relapse within these 2 years could be salvaged. Future directions in the treatment of MLCL will not focus on further dose intensification, but rather on the incorporation of (radio)immunotherapy as a therapeutic tool and gene expression profiling as well as positron emission tomography–computed tomography as stratifying tools

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

“…Prior to the introduction of rituximab, the combination of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) followed by radiotherapy (RT) had been considered suboptimal treatment for PMLBCL with cure rates generally not exceeding 50-60% [5,[11][12][13]. Combinations of methotrexate (or etoposide), doxorubicin, cyclophosphamide, vincristine, prednisone and bleomycin known as M(V) ACOP-B [14,15], dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (da-EPOCH) [16], Burkitt-like or acute lymphoblastic leukemia-like regimens such as the Memorial and GMALL protocols [12,17,18], and even consolidation of first-line response with high-dose therapy and autologous stem cell transplantation [5] have all been considered superior to CHOP in rather small-to medium-sized patient series, albeit without head-to head randomized comparison. The introduction of rituximab greatly improved the results of CHOP.…”

Radiation Therapy in Primary Mediastinal B-Cell Lymphoma With Positron Emission Tomography Positivity After Rituximab Chemotherapy

“…Singleinstitution or multiinstitution studies, mainly retrospective, showed that the combination of chemotherapy with CHOP (Cyclophosphamide, Doxorubicin, Vincristine, Prednisone) or CHOP-like regimens and radiation therapy (RT) is highly effective, given the peculiarity of the disease presentation and the tendency to recurrence in the primary site of origin 3, 4, 5 and 6. In the rituximab era, current standard therapy is represented by a combination of chemotherapy (CHOP, CHOP-like, EPOCH -Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin, M/VACOP-B -Methotrexate/Etoposide, Doxorubicin, Cyclophosphamide, Vincristine, Prednisone and Bleomicine) and rituximab followed by RT, with a higher response rate to rituximab chemotherapy (R-CT) when in comparison with chemotherapy alone 7, 8 and 9. Inasmuch as the outcomes are still unsatisfactory in a limited number of patients, with global overall survival rates of approximately 80%, more aggressive programs have been investigated, including strategies evaluating high-dose chemotherapy and autologous stem cells transplantation upfront (10). The need of consolidation RT has also been questioned in patients in complete remission after R-CT (11).…”

High efficacy of intensive immunochemotherapy for primary mediastinal B-cell lymphoma with prolonged follow up

“…In GMALL/B-ALL/NHL2002 regimen they have been moved to front line therapy to minimize risk of developing resistance to chemotherapy 17 . The GMALL/B-ALL/NHL2002 produced 90% ORR and 80% CR in PMBL patients 28 . After a median follow up of 8.6 years, 73% of patients achieved long-term disease free survival more than 2 years after start of therapy 28 .…”

“…The GMALL/B-ALL/NHL2002 produced 90% ORR and 80% CR in PMBL patients 28 . After a median follow up of 8.6 years, 73% of patients achieved long-term disease free survival more than 2 years after start of therapy 28 . Our preliminary experience with GMALL/B-ALL/NHL2002 was promising 13 , 14 .…”