A maintenance treatment with thalidomide at 100 mg a day was safe and seen to delay disease progression by more than three years in multiple myeloma patients with stable disease in a Phase 2 study in Japan, researchers report.
Data from the 34-patient trial were published in the International Journal of Hematology in the study, “Thalidomide maintenance therapy in Japanese myeloma patients: a multicenter, phase II clinical trial (COMET study).”
Outcomes for multiple myeloma patients have greatly improved with the use of chemotherapy and stem cell transplants. But most eventually relapse, making this a largely incurable disease.
Research has focused on maintenance treatments that prolong responses to standard approaches.
Thalidomide, an immunomodulatory medicine marketed in the U.S. as Thalomid by Celgene, has shown benefits as a maintenance treatment in patients who underwent a transplant. But reports are conflicting among those not eligible for transplant surgery. “[T]he efficacy of thalidomide maintenance therapy on its own and the optimal dose … were not clarified in these studies,” the study noted.
To fill this gap, researchers conducted a Phase 2 clinical trial, named COMET (UMIN 000006182), to examine the safety and efficacy of thalidomide maintenance therapy among Japanese myeloma patients.
It enrolled 34 people (median age of 74) who had received between one and three prior lines of treatment before achieving at least stable disease. Most (76.5%, 26 people) were newly diagnosed and were responding to a first-line treatment; the other eight (23.5%) had relapsed disease.
After an induction therapy selected for each person by their physician, six patients were reported to be in complete response, 12 had a very good partial response, 11 a partial response, and five had stable disease.
Patients were then randomized to one of two thalidomide doses — 50 mg or 100 mg per day — or to a no maintenance therapy group. Maintenance therapy continued until evidence of disease progression or severe adverse events.
Thalidomide was given to 22 patients overall for a median of between 13.2 and 14.2 months, which the researchers reported increased the depth of response to induction therapy in three people and a sustained response in eight others.
At two years, 77.8% of patients given 100 mg thalidomide were alive and progression-free, compared to 25% of the 12 people without this maintenance treatment — a statistically significant improvement. No differences, however, were seen between those given thalidomide at 50 mg (33.3%) and those without this maintenance treatment.
Progression-free survival at two years was this study’s primary goal, or endpoint.
Thalidomide treatment at 100 mg also extended the time to disease progression or death by more than three years compared to no maintenance treatment. Patients in the high-dose group lived without their disease worsening for a median of 42.9 months, versus 12.1 months for those given the 50 mg treatment, and 4.4 months for those without a maintenance treatment.
No significant difference in median overall survival, from the initiation of maintenance therapy, was seen among the three study groups.
Overall, daily maintenance therapy with thalidomide at 100 mg was found to be effective in stalling progression in multiple myeloma Japanese patients. The therapy’s effects were not affected by the type of induction therapy used, the researchers reported.
Treatment was generally well tolerated, with no patients discontinuing due to adverse events. The most common adverse events were constipation, dizziness, swelling, fatigue, and nausea.
“The current study demonstrates that maintenance with daily thalidomide at 100 mg, but not 50 mg, improved depth of response and prolonged PFS [progression-free survival], and that this treatment was feasible for use in Japanese multiple myeloma patients,” the researchers conclude.
Additional studies are warranted, they added, to confirm these findings in larger groups of myeloma patients.