Advertisement

Faster Rituximab Infusion for Previously Untreated Follicular Non-Hodgkin and Diffuse Large B-cell Lymphomas 


Advertisement
Get Permission

On October 19, 2012, FDA approved a 90-minute infusion for rituximab (Rituxan) starting at cycle 2 for patients with previously untreated follicular non-Hodgkin or diffuse large B-cell lymphoma who do not experience a grade 3 or 4 infusion-related reaction during cycle 1.1 Patients with clinically significant cardiovascular disease and those with high circulating lymphocyte counts (≥ 5,000/µL) before cycle 2 should not receive the faster infusion.

The non-Hodgkin lymphoma indications affected by the approval are previously untreated follicular, CD20-positive, B-cell non-Hodgkin lymphoma in combination with first-line chemotherapy and previously untreated diffuse large B-cell lymphoma in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or other anthracycline-based chemotherapy regimens.

The recommended dose of rituximab in non-Hodgkin lymphoma is 375 mg/m2 via IV infusion given on day 1 of each cycle of chemotherapy for up to eight doses in both follicular non-Hodgkin and diffuse large B-cell lymphoma patients. For the initial dose in cycle 1, rituximab infusion is initiated at a rate of 50 mg/h; in the absence of infusion toxicity, the rate is increased by 50 mg/h increments every 30 minutes to a maximum of 400 mg/h.

New Infusion Recommendations

Under the new approval, a 90-minute infusion can be administered in cycle 2 with a glucocorticoid-containing regimen in patients who do not experience a grade 3 or 4 infusion-related adverse reaction in cycle 1. The 90-minute infusion is started at a rate of 20% of the total dose given in the first 30 minutes, with the remaining 80% of the total dose given over the next 60 minutes. If the 90-minute infusion is tolerated in cycle 2, the same rate can be used when administering the remainder of the treatment regimen (through cycle 6 or 8).

RATE Trial Details

Approval of the faster infusion rate is based on findings in an open-label, single-arm, multicenter phase III trial (RATE trial) in which 363 patients with previously untreated follicular non-Hodgkin lymphoma (n = 113) or diffuse large B-cell lymphoma (n = 250) received rituximab 375 mg/m2 plus CVP (cyclophosphamide, vincristine, prednisone) in follicular non-Hodgkin lymphoma patients and CHOP in diffuse large B-cell lymphoma patients.2 Patients with clinically significant cardiovascular disease were excluded from the study.

Patients were eligible for a 90-minute rituximab infusion in cycle 2 if they did not experience a grade 3 or 4 infusion-related adverse event in cycle 1 and had a circulating lymphocyte count < 5,000/µL before cycle 2. All patients were premedicated with acetaminophen and an antihistamine and received the glucocorticoid component of their chemotherapy prior to rituximab infusion. Patients who tolerated the 90-minute infusion in cycle 2 continued to receive subsequent rituximab infusions at this rate for the remainder of the treatment regimen (through cycle 6 or 8).

Infusion-related Reactions

The main outcome measure of the trial was the development of grade 3 or 4 infusion-related reactions on the day of or the day after the 90-minute infusion in cycle 2. The incidence of grade 3 infusion-related reactions in cycle 2 was 1.1% (95% confidence interval [CI] = 0.3%–2.8%) among all patients, including an incidence of 3.5% (95% CI = 1.0%–8.8%) in follicular non-Hodgkin lymphoma patients (who received CVP) and 0.0% (95% CI = 0.0%–1.5%) in diffuse large B-cell lymphoma patients (who received CHOP). No grade 4 or 5 infusion-related reactions were reported in cycle 2. These results are comparable to those reported for cycle 2 in rituximab trials using the standard infusion regimen.

For cycles 2 through 8, the incidence of grade 3 or 4 infusion-related reactions was 2.8% (95% CI = 1.3%–5.0%). No acute fatal infusion-related reactions were observed. ■

References

1. US Food and Drug Administration: Rituximab infusion. Available at http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm324890.htm. Accessed November 9, 2012.

2. RITUXAN® (rituximab) injection for intravenous use prescribing information, Biogen Idec Inc and Genentech, Inc, October 2012. Available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/103705s5367s5388lbl.pdf. Accessed November 9, 2012.


Advertisement

Advertisement



;
Advertisement

By continuing to browse this site you permit us and our partners to place identification cookies on your browser and agree to our use of cookies to identify you for marketing. Read our Privacy Policy to learn more.