Landmark Trials in Selected Lymphomas

Abstract

This chapter contains a summary of some key findings from a selection of 26 trials related to patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, and classical Hodgkin’s lymphoma.

For DLBCL, 13 studies are discussed including those that helped produce the International Non-Hodgkin’s Lymphoma Prognostic Factors Project International Prognostic Index (IPI) and the updated NCCN-IPI. The long-term results of the SWOG S8736 trial which included patients with early-stage DLBCL treated in the pre-rituximab era as well as results from SWOG S0014 which treated patients in the post-rituximab era are discussed. Two GELA trials conducted in the pre-rituximab era comparing CHOP chemotherapy plus radiation therapy to alternative systemic therapy regimens are discussed. The key findings from multiple trials evaluating CHOP or CHOP-like chemotherapy regimens plus or minus rituximab are discussed including the LNH-98.5 trial, the MInT trial, and RICOVER-60. Recent studies that have evaluated the role of radiation therapy are included including the RICOVER-noRTh analysis which studied the role of irradiation following systemic therapy for patients with bulky sites of disease and a study by Aviles et al. that studied the role of post-chemotherapy radiation therapy for patients with residual masses on CT imaging. Chimeric antigen receptor (CAR) T-cell therapies targeting CD19 could transform management of patients with B-cell lymphoma, and the 2-year results of the ZUMA-1 trial are discussed.

For follicular lymphoma, four studies including the GELF 86 trial that established the GELF criteria of low-tumor burden is included as is the International Follicular Lymphoma Prognostic Factor Project that established the updated FLIPI2 prognostic index. A retrospective review of long-term outcomes of patients with stage I and II low-grade follicular lymphoma treated with irradiation at Stanford University is included. The key findings from the PRIMA trial that evaluated the role of maintenance rituximab are discussed.

For Hodgkin’s lymphoma, nine trials are included in this chapter including trials of historical interest by Press et al. and Bonaddona et al. that helped eliminate the standard use of staging laparotomy and shrink conventionally used radiation therapy field sizes. In favorable early-stage patients, the G4 trial used Stanford V and the German HD 10 trial helped reduce the number of cycles of ABVD chemotherapy and the dose of radiation therapy. The key findings from the UK RAPID trial that evaluated a PET-response based de-escalation strategy are discussed. In early-stage unfavorable patients, the HD11 trial evaluated four different treatment regimens. Finally, for patients with advanced stage disease, three randomized trials that evaluated the optimal treatment regimen including a randomized trial by the CALGB, the ECOG E2496 trial, and HD 11 are included.

There are hundreds of trials to choose from, and therefore, no claim toward completeness can be made in the current format. These trials relate to the multidisciplinary management of lymphomas from the perspective of a radiation oncologist. Readers are encouraged to refer to the full manuscript of these trials for a greater understanding. This material is provided for educational purposes only and with the goal of encouraging further study about the landmark trials that have impacted oncology.