Ofatumumab as a Single Agent
Results of ofatumumab administered as a single agent with an extended induction (initial treatment) brought about a high response rate and it was well tolerated among follicular lymphoma patients, according to a recent article in Cancernetwork.
These patients, who did not receive prior treatment, were in an advanced stage of follicular lymphoma with a low/intermediate Follicular Lymphoma International Prognostic Index (FLIPI) score.
About the Phase II Study
The phase II study was published in the British Journal of Haematology. Researchers were of the opinion that ofatumumab may exhibit a significant benefit in patients with advanced disease that presented with lower tumor burden and had not previously been treated with rituximab.
Initially, one arm of the Phase II trial had involved administering 500-mg. But it was abandoned due to an insufficient number of participants. The second arm involved 36 patients who received a 1,000-mg dose for four weeks followed by a total of four extended-induction doses which were administered once every eight weeks.
Trial results for administering the 1,000-mg dose are as follows:
- the overall response rate was 84%
- the median duration was 23.7 months
- at 12 months 9% of patients achieved a complete response
- 75% achieved partial response
- 9% had stable disease
The majority of patients (66%) who exhibited a complete or partial response to therapy achieved this level by the third month.
Primary Endpoint
There are several goals for most clinical trials. One primary endpoint involves the relative safety and efficacy of the drug being tested. Then a critical point is that the drug must provide a substantial improvement over current drugs in order to receive further evaluation.
If a treatment is found to be relatively safe and effective, it is then evaluated in a phase 3 trial to see if it is more effective than standard treatments available, or has fewer side effects than standard treatments. If a drug is found to be more effective or safer in a phase 3 trial, it may then be evaluated for FDA approval.
The researchers reported that “Durability of response to extended-induction ofatumumab in this study appears inferior to that reported for similar extended-dosing regimens of rituximab monotherapy in chemotherapy-naive, low-tumor-burden FL.”
About Follicular Lymphoma (FL)
Follicular lymphoma, a form of non-Hodgkin lymphoma, occurs in a type of white blood cells called lymphocytes, an important part of the immune system that fights off infection. FL causes the build-up of these white blood cells in blood, bone marrow, and lymph nodes. The spleen may also be affected. Approximately one in three thousand people may be affected by FL at a median age of between 60 and 65 years. It rarely affects children.
Symptoms of FL
Possible symptoms are fatigue, fever, night sweats, and enlarged lymph nodes. Painless swelling on the body may occur on the underarm, neck or groin. It is a slow-growing type of lymphoma and does not always require immediate treatment.
Ofatumumab vs. Rituximab
A trial comparing ofatumumab and rituximab in the relapsed and treatment resistant setting failed to show the superiority of ofatumumab.
The report showed these results for patients in the 1,000 mg group at a median follow up for 30.7 months:
- 31% of patients remain in remission
- 1-year progression-free survival (PFS) was 90%
- median progression-free survival was 8 months
- prolonged median event-free/PFS durations of 34–42 months were comparatively observed in studies of rituximab extended-induction dosing.
Obinutuzumab vs. Rituximab
Significantly prolonged progression-free survival (PFS) in patients with previously untreated follicular lymphoma (FL) was observed when treated with obinutuzumab, and also when it was combined with other chemotherapy. The results were reported in the GALLIUM study, published in the Journal of Clinical Oncology.
However, it is noteworthy that there have been no studies of obinutuzumab as a single agent in advanced FL patients with low tumor burden.
Obinutuzumab Plus CHOP
The combination of obinutuzumab, CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) and bendamustine is highly active in patients with untreated FL. The efficacy is similar to rituximab-based immunochemotherapy.
Conclusion
The researchers wrote “Whether there is clinical benefit of single-agent ofatumumab or obinutuzumab over rituximab in treatment-naive patients with lower tumor burden remains unanswered.”
