PET-Based Radiotherapy Strategy Found Safe for Bulky Disease in Elderly Patients

PET-Based Radiotherapy Strategy Found Safe for Bulky Disease in Elderly Patients

Dr. Jane N. Winter discusses Abstract 7506.
A planned interim analysis of the OPTIMAL˃60 trial found that a PET-based radiotherapy (RT) strategy to treat bulky disease is safe in elderly patients with diffuse large B-cell lymphoma (DLBCL). In the Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia Oral Abstract Session on June 3, Michael Pfreundschuh, MD, of the University Saarland Medical School, in Germany, said that RT can be spared in elderly patients with DLBCL with PET-negative bulky disease after immunochemotherapy without compromising their outcome (Abstract 7506).

“The interim analysis results demonstrate that a PET-based RT strategy for bulky disease is safe…and results in a reduction of radiotherapy by 42%,” Dr. Pfreundschuh said.

He also said that RT appears to compensate for the assumed worse prognosis of PET positivity. A previous trial, RICOVER-60,1 published in 2014, found that additive RT to bulky sites abrogated bulky disease as a risk factor and improved the outcome for elderly patients.

The OPTIMAL˃60 trial prospectively addressed whether RT could be avoided in patients with PET-negative disease after treatment with rituximab/cyclophosphamide/doxorubicin hydrochloride/vincristine sulfate/prednisone (R-CHOP). Patients age 61 to 80 from 88 institutions were randomly assigned in a 2x2 factorial design to six cycles of CHOP-14 or six cycles of cyclophosphamide/doxorubicin/liposomal vincristine/prednisone (CHLIP-14) plus eight cycles of 375 mg/m2 rituximab every 2 weeks or 12 cycles of rituximab on specified days. Patients with 7.5-cm or greater bulk with PET-positive disease after six cycles of chemotherapy were assigned to 39.6 Gy RT; the patients with PET-negative bulk were observed, Dr. Pfreundschuh said.

A planned interim analysis was conducted after 40% of expected events. A historical comparison looked at the patients in RICOVER-60 who had received six cycles of CHOP-14 plus two cycles of rituximab, in addition to RT to the original bulky area.1 Thirty-three percent of patients in RICOVER-60 were older than age 70 compared with 49% in OPTIMAL˃60 (p = 0.007).

PET was performed in 166 of the 187 patients with bulky disease in OPTIMAL˃60, and 80 of the 166 patients with bulky disease were still PET positive after six cycles of chemotherapy; 62 of those 80 patients received RT. Two-year progression-free survival was 79% for the 47 patients who received PET-based RT and were treated with six cycles of CHOP-14 and eight cycles of rituximab. In comparison, the RICOVER-60 study reported 75% progression-free survival for its 117 patients (p = 0.602). Overall survival for those same groups of patients was 88% for OPTIMAL˃60 and 78% for RICOVER-60 (p = 0.307).

Discussant Jane N. Winter, MD, of the Feinberg School of Medicine at Northwestern University and the Robert H. Lurie Comprehensive Cancer Center, noted the declining use of RT for treatment of DLBCL in the United States.

“One of the unsettled issues for me is whether irradiation of PET-positive bulky disease improves outcomes. The patients in this trial did extremely well with RT. These outstanding outcomes for PET-positive patients are provocative and very supportive of radiating these individuals; however, I would like to learn more about them and which ones did not get RT. When the study is completed with an additional 60% of the planned enrollment, it will be very interesting to look at those subset analyses.”

Dr. Winter explained that radiotherapy may be safely omitted for elderly patients with advanced-stage, bulky disease that is PET-negative after completing a full course of rituximab. “Radiotherapy may salvage many patients with positive end-of-therapy PETs,” she said. “However, it remains controversial what the optimal therapy is for early-stage bulky disease in elderly patients and whether that should be abbreviated rituximab chemotherapy with or without RT.”

  –Kathy Holliman, MEd