Benefit of Extended Rituximab Exposure in Poor-Prognosis Elderly Patients With Diffuse Large B-Cell Lymphoma
In the phase II SMARTE-R-CHOP-14 trial of the German High-Grade Non-Hodgkin Lymphoma Study Group reported in the Journal of Clinical Oncology, Pfreundschuh et al found that extended rituximab (Rituxan) exposure in patients aged > 60 years with poor-prognosis diffuse large B-cell lymphoma was associated with increased event-free survival and overall survival compared with historical controls.
Study Details
In the SMARTE-R-CHOP-14 trial, 189 patients received six cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone on a 14-day schedule (6 × R-CHOP-14) and rituximab at 375 mg/m2 given on days −4, 0, 10, 29, 57, 99, 155, and 239. Outcomes were compared with those in patients receiving 6 × R-CHOP-14 in combination with eight administrations of rituximab given every 2 weeks in the RICOVER-60 trial. The two trials had identical inclusion and exclusion criteria.
Outcomes
The complete response/unconfirmed complete response rate was 85%, including 90% in 90 good-prognosis patients (International Prognostic Index [IPI] score 1 or 2), and 81% in 99 poor-prognosis patients (IPI score 3–5). Three-year event-free survival was 71%, 75%, and 67% among all patients, good-prognosis patients, and poor-prognosis patients, and 3-year overall survival was 84%, 88%, and 80%.
Increased Benefit in Poor-Prognosis Patients
Compared with outcomes in 306 patients in RICOVER-60, including 183 good-prognosis patients and 123 poor-prognosis patients, there were no differences in event-free survival or overall survival overall or among good-prognosis patients. However, the SMARTE-R poor-prognosis patients had better 3-year event-free survival (67% vs 54%) and 3-year overall survival (80% vs 67%).
Toxicity
There were no significant differences in grade 3 or 4 adverse events in patients in the SMARTE-R trial vs those in RICOVER-60, except for lower frequencies of leukopenia (42% vs 52%) and infection (19% vs 28%) in the SMARTE-R patients.
The investigators concluded: “Extended rituximab exposure compared with eight 2-week applications in combination with 6 × R-CHOP-14 significantly improved outcome of elderly poor-prognosis patients without increasing toxicity. To our knowledge, results obtained with the SMARTE-R-CHOP-14 rituximab schedule are the best reported for elderly patients with diffuse large B-cell lymphoma to date. In the subgroup of poor-prognosis patients treated with extended rituximab exposure, the outcome seemed superior to that of a similar historical cohort of patients treated with 6 × R-CHOP-14 plus 2-week rituximab, with similar toxicity. A randomized comparison of the two schedules is warranted.”
Michael Pfreundschuh, MD, of Saarland University Medical School, Homburg, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported by Deutsche Krebshilfe and Roche (funded pharmacokinetic studies). For full disclosures of the study authors, visit jco.ascopubs.org.
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