Anti-CD20 monoclonal antibodies, such as ofatumumab and rituximab, have been demonstrated to be effective in B-cell Lymphoma and CLL. However, the recommended administration of ofatumumab for CLL requires lengthy infusion times and side effects are common during and after infusion.
On 7th July 2017, in The Oncologist, William Donnellan, MD, from the Sarah Cannon Research Institute and Tennessee Oncology, PLLC, Nashville, Tennessee, USA, and colleagues published results of their phase II, single-arm study, which evaluated an accelerated infusion regimen (2 hours) of ofatumumab in patients with metastatic or advanced Chronic Lymphocytic Leukemia (CLL) who had received one or more prior therapies.
Overall, 34 patients were treated with a median age of 70 years (range, 53–89) and a median of 1 prior systemic therapy (range, 1–5). Non-mutated IgVH was observed in 53% of patient (n=18). Furthermore, 13 patients (38%) were CD38-positive, 8 (24%) harbored del(11q), and 6 patients (18%) had del(17p). The primary endpoint of the study was to identify the number of patients who were able to complete rapid infusion 3 within 15 minutes of the planned 2-hour therapy.
Schedule of administration:
- 28-day cycle with ofatumumab
- Day 1 – 300mg, starting at 3.6mg/hr then doubling every 30 mins until 240mg/hr was reached
- Day 3 – 1,000mg, starting at 50mg/hr then doubling every 30 mins until 800mg/hr was reached
- Day 8 – 2,000mg, given on week 2 day 1 at 800mg/hr over the first 30 mins and at 1,068mg/hr over the next 90 mins (goal infusion time, 120 mins)
- Response assessment (n=31):
- ORR = 19% (6 pts; all PR)
- SD = 71% (22 pts)
- PD = 10% (3 pts)
- Unevaluable in 10% (3 pts)
- Ninety-seven percent of pts completed the third infusion and 87% of pts completed it ≤15 mins of the planned 2-hours
Adverse Events (AEs):
- The most common all-grade AEs (≥10% of pts) were decrease in platelet count (21%) and decrease in neutrophil count (15%)
- Five SAEs were reported: grade 3 anemia, grade 3 urinary tract infection, grade 3 loss of consciousness, grade 3 pneumonia, and grade 5 cardiac arrest
- Infusion related reactions (IRRs):
- The proportion of pts who experienced an IRR of any-grade decreased at each infusion: infusion 1 = 62%; infusion 2 = 12%; infusion 3 = 3%
- Grade 3 IRRs: infusion 1 = 3 (shortness of breath, face flushed, and hives); infusion 2 = 1 (shortness of breath); infusion 3 = none
The authors concluded by stating that rapid infusion of ofatumumab using a stepped-up dosing regimen appeared safe and was well tolerated. The study also demonstrated the feasibility of decreasing the incidence of IRRs using this approach. Also, they drew attention to the fact that the second dose of ofatumumab was given just two days, rather than the standard one week, after the first dose. Lastly, the authors stated that this rapid infusion approach “addresses quality-of-life concerns” meaning that patients spend less time in the clinic, therefore having more time to “spend doing more pleasurable activities.”
LESSONS LEARNED: Ofatumumab infusion reactions can be diminished by escalating the dose rate in individual patients in sequential infusions.
BACKGROUND: Ofatumumab (OFA) is a fully humanized, anti-CD20 antibody approved for use in chronic lymphocytic leukemia (CLL). The recommended administration requires long infusion times. We evaluated an accelerated infusion regimen of 2 hours.
METHODS: The first dose of OFA (300 mg) was given on week 1 day 1 starting at 3.6 mg/hour and doubling every 30 minutes until a rate of 240 mg/hour was reached. If tolerated, the second dose (1,000 mg) was given on week 1 day 3 starting at 50 mg/hour and doubling every 30 minutes until a rate of 800 mg/hour was reached. If tolerated, the third dose (2,000 mg) was given on week 2 day 1 at 800 mg/hour over the first 30 minutes and, if tolerated, at 1,068 mg/hour over the next 90 minutes (goal infusion time: 120 minutes). Subsequent OFA infusions were administered weekly in the same manner for 8 weeks, and then monthly for 4 months.
RESULTS: Thirty-four patients were treated. Most infusion-related reactions occurred during the first and second infusion. Eighty-seven percent (87%) of patients finished the third infusion within 15 minutes of the planned 2 hours and only one had an infusion reaction.
CONCLUSION: Using this stepped-up dosing regimen, a rapid infusion of OFA is safe and well tolerated.
1. Donnellan W. et al. A Phase II Trial Evaluating the Safety of Rapid Infusion of Ofatumumab in Patients with Previously Treated Chronic Lymphocytic Leukemia. The Oncologist. 2017 Jul 7. pii: theoncologist.2017-0236. DOI: 10.1634/theoncologist.2017-0236. [Epub ahead of print].