Researchers involved in an international Phase II study have reported that ofatumumab, an anti-CD20 antibody, is effective in patients with chronic lymphocytic leukemia (CLL) who have previously received Rituxan® (rituximab). The details of this study were reported at the 2009 meeting of the American Society of Clinical Oncology on May 30, in Orlando, Florida.[1]
Ofatumumab (HuMax-CD20) inhibits early-stage B lymphocyte activation. It is under development for treatment of B-cell lymphoid malignancies and rheumatoid arthritis. A Phase I-II study was carried out in 33 patients with refractory B-cell CLL.[2] A maximum tolerated dose was not reached in this study. Toxicities were related to early infusions, which diminished with further infusions. More than half the patients developed infections, with one fatal interstitial pneumonia. The response rate was 50%. A second Phase I-II study was carried out in 40 patients with refractory follicular lymphoma treated at four different dose levels.[3] Patients in this study had “profound” B-cell depletion, and 65% reverted to a BCL2 negative status. Response rates ranged from 20% to 63%. The median response duration for responders was 30 months.
At ASH 2008 researchers involved in an International Phase II study reported that ofatumumab was effective for the treatment of patients with CLL who have failed Fludara® (fludarabine) and Campath® (alemtuzumab) (double refractory) or who had failed Fludara and had bulky disease.[4] At ASCO 2009 researchers presented an update of the data presented at ASH 2008 with emphasis on the effects of prior exposure to Rituxan. This study involved 138 patients who were refractory to Fludara and Campath (n=59) or were refractory to Fludara and had bulky disease (n=79). The main new findings presented at ASCO 2009 were as follows:
- In double-refractory patients the overall response rate was 54% in patients with any prior exposure to Rituxan and 63% in patients who had no prior exposure to Rituxan.
- In double-refractory patients median progression-free survival was 5.5 months for patients with any prior exposure to Rituxan compared with 7.1 months in patients who had no prior exposure.
- In bulky Fludara-refractory patients, the overall response rate was 44% for patients with any prior exposure to Rituxan compared with 50% for patients with no prior exposure to Rituxan.
- In bulky Fludara-refractory patients, the median progression-free survival was 5.5 months for patients with any prior exposure to Rituxan compared with 6.4 months for patients with no prior exposure to Rituxan.
These authors concluded: “Single-agent therapy with ofatumumab is effective in patients with doubly refractory or bulky fludara refractory CLL.”
Comments: These data confirm that many patients with refractory CLL who have failed Rituxan therapy will respond to ofatumumab.
References:
[1] Wierda WG, Kipps T, Mayer J, et al. Activity of ofatumumab, a novel CD20 mAB, and prior rituximab exposure in patients with fludarabine- and alemtuzumab-refractory or bulky fludarabine-refractory chronic lymphocytic leukemia (CLL). Journal of Clinical Oncology. 2009;27:15s, abstract number 7044.
[2] Coiffier B, Lepretre S, Pedersen LM, et al. Safety and efficacy of ofatumumab, a fully human monoclonal anti-CD20 antibody, in patients with relapsed or refractory B0cell chronic lymphocytic leukemia: a phase 1-2 study. Blood. 2008;111:1094-1100.
[3] Hagenbeck A, Gadeberg O, Johnson P, et al. First clinical use of ofatumumab, a novel fully human anti-CD20 monoclonal antibody in relapsed or refractory follicular lymphoma: results of a phase 1/2 trial. Blood. 2008;111:5486-5495.
[4] Kipps TJ, Mayer J, Stilgenbauer S, et al. Ofatumumab (JuMax-CD-20), a novel CD20 monoclonal antibody, is an active treatment for patients with CLL refractory to both fludarabine and alemtuzumab or bulky fludaravine-refractory disease: Results from the planned interim analysis of an International Pivotal Trial. Blood. 2008;112:126, abstract number 328.
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