Celgene Corporation announced that Paul Richardson, of the Dana-Farber Cancer Institute at Harvard University presented preliminary results from a randomized Phase II trial of Revimid (CC-5013) in relapsed or refractory multiple myeloma at the American Society of Hematology annual meeting (ASH). The data demonstrate that 39 of 46 evaluable patients (85 per cent) with progressive disease experienced a reduction or stabilization in their paraprotein levels (a measure of tumor burden).

Importantly, five of seven patients who experienced progressive disease on Revimid monotherapy subsequently experienced a reduction or stabilization of paraprotein levels after Revimid plus dexamethasone combination therapy. Therefore, 44 of 46 evaluable patients (96 per cent) experienced a reduction or stabilization of paraprotein levels after either Revimid monotherapy or Revimid plus dexamethasone combination therapy.

The Phase II trial evaluated two dose regimens of Revimid in relapsed or refractory multiple myeloma patients, the majority of whom had both relapsed and refractory disease despite intensive prior therapy. Seventy patients have enrolled in the trial with 57 patients evaluable for toxicity and 46 patients evaluable for response. The median patient age is 62 years and patients have received a median of four prior regimens (range one to ten) including 23 patients who have undergone stem cell transplants and 23 patients who have received prior thalidomide therapy. Patients were randomized to receive either 15 mg of Revimid twice a day or 30 mg of Revimid once a day. Both doses were administered for three weeks followed by one week of rest. Dexamethasone was administered at 40 mg/day for four days every two weeks to patients who had progressive disease after four weeks of therapy. Patients who did not experience a greater than 25 per cent reduction in paraprotein levels after eight weeks were given dexamethasone.

Two of 46 evaluable patients (9 per cent) achieved a complete paraprotein response. Eight patients (17 per cent) achieved a partial response defined by a greater than 50 per cent reduction of paraprotein levels and 15 patients (33 per cent) achieved a minimal response defined by a greater than 25 per cent reduction. Fourteen patients (30 per cent) achieved disease stabilization. Only seven of 46 patients experienced disease progression on Revimid monotherapy, and of these seven patients, four achieved at least a minimal response and one achieved disease stabilization on subsequent Revimid plus dexamethasone combination therapy.

Similar overall response rates were observed between the two Revimid dose regimens; however, patients tolerated the 30 mg once-daily dose of Revimid better than the 15 mg twice-daily dose. Eleven patients (41 per cent) who received the 15 mg twice-daily dose of Revimid required dose reduction due to grade three or four myelosuppression as compared to four patients (13 per cent) who received the 30 mg once-daily dose of Revimid. One patient who had grade two neuropathy from previous therapy experienced grade three neuropathy after three months of the 30 mg once-daily dose of Revimid. No other grade three non-hematological toxicities were observed. Grade one or two diarrhea, fever, muscle cramps, neuropathy, constipation, rash and fatigue were observed.

There are approximately 50,000 people in the United States living with multiple myeloma, and about 14,600 new cases of multiple myeloma are diagnosed each year, making it the second most common blood cancer. Multiple myeloma is a malignant cancer of the plasma cell, which is a type of white blood cell found in the bone marrow. As the cancer grows it destroys normal bone tissue, causing pain and crowding out normal cell production. About 10,800 Americans (5,500 men and 5,300 women) are expected to die of multiple myeloma in 2002.