Thalidomide: ‘Striking’ Activity in Myeloma

ASCO—Updated findings on thalidomide (Thalomid) for the treatment of refractory myeloma show “striking results,” Bart Barlogie, MD, PhD, director of the Arkansas Cancer Research Center, Little Rock, said at the 36^th Annual Meeting of the American Society of Clinical Oncology (ASCO), in New Orleans.

In a study of 180 patients treated with single-agent thalidomide, a 25% paraprotein reduction was achieved in 36% of patients and was apparent in more than 80% within 2 months. Twenty percent of patients attained a complete or near-complete response. Paraprotein responses were accompanied by comparable reduction in bone marrow plasmacytosis and recovery of hemoglobin platelet levels.

“We confirm the previous response data, and show rather extended survival in this very poor risk population of patients with fairly end-stage disease,” Dr. Barlogie said at a poster session. “I think with what we have done in the past, the average survival would have been 4 to 6 months. I don’t think more than 10% of patients would have been alive 2 years later. These data showing 40% survival at 24 months are very encouraging.”

In this study, the maximum tolerated dose (400 mg) produced durable paraprotein reduction in refractory patients without significant myelosuppression, making it suitable for combination with myelosuppressive chemotherapy regimens, Dr. Barlogie said.

Forty-four percent of the patients in the study were over 60 years of age; 77% of these cases had received at least one previous autologous transplant, and 53% had received two. “The results of this study are stunning—especially when one considers that these patients had failed all other therapy,” Dr. Barlogie said.

Thalidomide is believed to be an angiogenesis inhibitor with the potential to inhibit new blood vessel formation, thus starving cancer cells of the blood supply they need to grow. But thalidomide may have other mechanisms of action as well. “It may have a potent immune function or kill myeloma cells directly,” Dr. Barlogie said.

Dr. Barlogie is now conducting several randomized trials of the 400 mg thalidomide dose in combination with chemotherapy. “We are looking for the greatest activity in multiple myeloma,” he said.

In one study, 23 patients in post-transplant relapse with low-tumor burden (bone marrow plasmacytosis of 30% or less) and low-risk disease (absence of chromosome 13 deletion) have been randomized to dexamethasone with or without thalidomide.

Sixty-six patients with high tumor mass or high risk of post-transplant relapse have been randomized to DCEP (dexamethasone, cyclophosphamide, etoposide, cisplatin) with or without thalidomide.

In a study of patients with more than one cycle of prior therapy, 157 patients have received D.T. PACE (thalidomide combined with DCEP plus Adriamycin). In patients with paraprotein reduction of 50% or more after two cycles of D.T. PACE, therapy with D.T. PACE is continued or patients are randomized to two cycles of melphalan (Alkeran) 200 mg/m2 with stem cell support (tandem transplants).

The Total Therapy II study has enrolled 186 patients with newly diagnosed myeloma, Dr. Barlogie said. “These patients are randomized upfront to receive or not to receive thalidomide during remission-induction therapy,” he said.

Induction therapy for Total Therapy II patients is very intensive, consisting of VAD (vincristine, Adriamycin, dexamethasone), DCEP, and CAD (cyclophosphamide, Adriamycin, dexamethasone). This is followed by two cycles of melphalan-based high-dose therapy with stem cell support. Patients are then further randomized to consolidation chemotherapy with DCEP every 3 months or DCEP alternating with CAD every 6 weeks for 1 year, and this is followed by interferon maintenance.

The results of all of these combination trials are pending, Dr. Barlogie said.