Page 158 - 18F-FDG PET as biomarker in aggressive lymphoma; technical and clinical validation

Chapter 6b
The dose and schedule of rituximab in the R-CHOP combination are largely empirically determined on historical grounds. Few phase II studies have explored variations of the rituximab schedule in combination with CHOP in elderly patients with DLBCL [7,8].In a single study in which patients were treated with rituximab administered in shorter intervals at the beginning of treatment and over a prolonged period of time, a better outcome for patients with poor prognosis with International Prognostic Index (IPI) score of 3 to 5 compared with historical controls was reported [8].The same group reported significantly reduced rituximab clearance in elderly women compared with elderly men [9].During standard R-CHOP-14 treatment, serum levels of rituximab show a gradual increase up to cycle 5, reaching a plateau thereafter [10].The lag time of 5 cycles may result in suboptimal rituximab serum levels, especially early during treatment. Therefore, treatment outcome may be improved through intensification of rituximab during the first 4 cycles by providing a steeper increase to the optimal therapeutic serum level as well as reaching a higher serum concentration within the large therapeutic window of rituximab [11,12].
To assess the efficacy of early rituximab intensification during first-line treatment in patients with DLBCL, we performed a prospective randomized phase III study to compare standard R-CHOP-14 with R-CHOP-14 combined with 4 extra administrations of rituximab during the first 4 induction cycles. Patients in complete remission (CR) after induction treatment were randomly assigned a second time between observation and rituximab maintenance. Here, we present the final analysis of the induction random assignment, including long-term follow-up data with a data cutoff of October 16, 2019.
Patients and methods
Patient Population
The HOVON-84 (Haemato Oncology Foundation for Adults in the Netherlands) study was an investigator-initiated prospective randomized phase III study conducted among 68 participating centers in the Netherlands, Denmark, and Belgium. The study was approved by the institutional review boards at all centers. Eligibility included previously untreated, biopsy-confirmed, CD20+ DLBCL according to local pathology and Ann Arbor stage II to IV. Patients between age 18 and 65
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