Infusion Speed-Escalation Trial To Give Full-Dose Rituximab in One Hour without Steroids Pre-Medication.

Abstract The first administration of rituximab can cause important side effects due to cytokine release into the blood. It is therefore recommended to administer it over 4–6 hours. According to the manufacturer subsequent doses can be given in approximately 3 hours, but this is demanding for the patient (pt) and facilities and resources-consuming. A Canadian study has recently shown that rituximab can be given safely over 90 minutes from the second administration in combination with CHOP, provided that steroids and chemotherapy are administered before the antibody. We are conducting an infusion speed-escalation trial to verify if rituximab can be given in one hour without steroids pre-medication, in pts having received at least two previous doses of rituximab (with or without chemotherapy) in the previous 3 months. Further inclusion criteria include a normal cardiac function as evaluated by ECG and echocardiography. Cohorts of 3 patients are assigned to receive rituximab at a given initial infusion speed, to be increased by 100 mg /hour every 30 minutes. All receive standard anti-hystamine and paracetamol pre-medication. At every subsequent rituximab administration the initial speed is increased by 100 mg/h (intra-patient speed-escalation). If a pt experiences serious adverse events (SAE), then 6 pts are treated in the same cohort, in case of SAE in 2 of them the trial is discontinued. In each new cohort the initial speed is 100 mg/hr higher than in the previous cohort. Pts are monitored every 15 minutes for symptoms, blood pressure and hearth rate, hourly for temperature and an ECG is performed after treatment. For patients receiving chemo-immunotherapy, rituximab is given first and chemotherapy only later on the same day. Fifteen pts have so far been included (14 evaluable), with the first 4 cohorts complete. Median age was 60 (range 41–76), lymphoma type was diffuse large cell (8 pts), follicular (4 pts) and other indolent (3 pts). Two patients were treated with single agent rituximab and 12 in combination with chemotherapy. The median time from the last rituximab to inclusion in the study was 3 weeks (range 1–11). Overall, 3 cycles were given at a starting infusion speed of 200 mg/hr, 7 cycles at 300 mg/hr, 11 cycles at 400 mg/hr, 11 cycles at 500 mg/hr, 8 cycles at 600 mg/hr and 7 cycles at 700 mg/hr. The latter schedule allowed the administration of the whole prescribed drug in one hour. All pts tolerated the increased-speed infusion without major side effects. The blood pressure dropped by a median 10–15% of baseline, without symptoms and without significant differences between cohorts. The highest blood pressure drops were of respectively 25% and 29% without symptoms and spontaneously resolving within 15 minutes. There was no variation in the hearth frequency and no elevation of body temperature above 37°C. No relevant ECG changes were seen. We conclude that rituximab can be given in one hour without steroids pre-medication in pts who have already received at least two previous rituximab doses. The study is ongoing to evaluate the maximum infusion speed and will further explore if the latter is applicable from the second infusion on.

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