Background: The PRIMA study showed that 2 years of R-M therapy after immunochemotherapy as first line treatment of follicular lymphoma reduced the risk of disease progression compared to OBS (Salles et al, Lancet 2011). Per-protocol analyses showed that R-M did not adversely affect patient-reported quality of life. Here we report detailed analyses on symptom burden and toxicity.
Methods: In the induction phase, patients received R-CHOP, R-CVP, or R-FCM, which was selected by the treatment center according to the investigator's routine practice. Patients who received 8 infusions of rituximab in combination with chemotherapy and achieved a complete response (CR) or partial response (PR) at the end of induction treatment (n=1,018) were randomized to receive either R-M therapy or OBS. After randomization, patients were treated every 8 weeks for 2 years or until disease progression.
The European Organisation for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire–Core 30 items (QLQ-C30) was assessed—prior to disease progression—at baseline, end of induction, 1 year of maintenance treatment, and end of 2 years of maintenance treatment. Symptoms were assessed using the 12 symptom items in the QLQ-C30. Safety data were collected for all patients using a checklist with Common Terminology Criteria for Adverse Events (CTCAE) grades, which were reported for each cycle of chemotherapy during induction and each 8-week period during the R-M/OBS period.
Results: The sample consisted of all patients entered into the maintenance phase who completed at least one observation or treatment (n=1,009). The assessment at the end of induction was considered baseline. At baseline, being tired (72%), need to rest (71%), feeling weak (61%), and trouble sleeping (57%) were the most frequently reported symptoms. These symptoms were followed by shortness of breath (39%), pain (34%), pain interfering with daily activities (31%), constipation (28%), and lack of appetite (24%). The least frequently reported symptoms were vomiting (4%), diarrhea (17%), and nausea (18%).
By the end of maintenance, notable improvement (percentage of patients with improved symptoms minus percentage with worsened symptoms of 5% or greater) was seen for fatigue symptoms, trouble sleeping, shortness of breath, lack of appetite, and nausea. No symptom was seen for which the percentage worsened minus percentage improved was greater than 3%. The percentage of patients with improved, stable (no change), and worsened symptoms was not significantly different between R-M and OBS groups for any symptoms (P >0.10).
Logistic regression with random intercept was used to evaluate the likelihood of having symptom improvement among patients with the symptom at maintenance baseline. Exploratory analyses suggests that those in the R-M group had almost twice the odds of improvement in pain as those in the observation group (OR=1.97; 95% CI, 1.03–3.79; P =0.04) after adjusting for time and pain severity at baseline. No significant difference was seen for any other symptom (P >0.05).
Hematologic toxicity was the most frequently reported toxicity at the beginning of maintenance (>20% of patients had leukocytosis). Patients with hematologic toxicity gradually decreased in both R-M (e.g., leukocytosis, 10% after 2 years of treatment) and OBS groups (5%).
Conclusion: These results suggested R-M did not negatively impact disease- or treatment-related symptoms and was generally comparable to no treatment. The rate of AEs was low and hematologic toxicity induced during chemotherapy treatment improved in the R-M/OBS phase.
