Randomized Phase II Trial of Thalidomide Alone versus Thalidomide Plus Interferon Alpha in Patients with Refractory Multiple Myeloma

Abstract

The potential synergistic anti-myeloma effect for thalidomide combining with interferon alpha was not yet clear clinically. From March 2001 to January 2004, a total of 28 heavily pretreated multiple myleoma (MM) patients were enrolled in this open-labeled, randomized Phase II study. Patients with refractory MM were randomized to receive either thalidomide alone (200 mg/day up to the maximum dose 800 mg/day, arm B) or the combination of thalidomide and interferon alpha (3 MIU/m(2) subcutaneous injection 3 times weekly, arm A). The objective of this study was to compare the safety and efficacy of thalidomide alone to combined regimen. The patients' characteristics were similar between the 2 arms. However, the average treatment duration was significantly longer in the arm B than the arm A (236 days versus 101 days, p = 0.029). Serum levels of paraprotein decline >/= 25 percent were obtained in 6 of 12 patients (50.0 percent) treated with arm B and 3 of the 16 patients (18.8 percent) treated with arm A. The estimated time to event was 7.9 months (95 percent confidence interval [95%CI], 0.5-15.4) for arm B and 1.5 months (95%CI, 0.0-3.4) for arm A (log-rank test, p = 0.0193). The major adverse events in both arms consisted of neutropenia, anemia, thrombocytopenia, constipation, somnolence, and skin rash. Our study showed that thalidomide alone was effective and tolerated in patients with relapsed or refractory MM. The thalidomide combined with interferon alpha resulted in a lower frequency of paraprotein response, shorter treatment-duration and 25 percent of patients' refusing rate. It may be concluded that the combined regimen is not well tolerated in our patients and needed to be further evaluated in the future.

Potential for all-trans retinoic acid [tretinoin] to enhance interferon-alpha treatment response in chronic myelogenous leukemia, melanoma, myeloma, and renal cell carcinoma

“…It is in wide use to treat chronic myelogenous leukemia, CML, 2,3 melanoma, 4,5 myeloma 6,7 and renal cell carcinoma, RCC. 8,9 IFNa is actually a family of a dozen related, approximately 166 amino acid, 16 to 20 kDa proteins.…”

Combination of IFN-α/Gm-CSF as a Maintenance Therapy for Multiple Myeloma Patients after Autologous Stem Cell Transplantation (ASCT): A Prospective Phase II Study

“…Thus, we suggest that IFN-α is not different than any of these new novel drugs and that expanded combination maintenance therapy, including GM-CSF and IFN-α, should be further investigated. Few studies have been published on combining interferon or peginterferon with thalidomide, [54][55][56] which showed high rate of adverse effects and intolerance to the combination. Another study reported the use of combination of 13 cis-retinoic acid, dexamethasone and IFN-α as maintenance for MM patients post ASCT.…”

Guidelines on the diagnosis and management of multiple myeloma treatment: Associação Brasileira de Hematologia e Hemoterapia e Terapia Celular Project guidelines: Associação Médica Brasileira - 2012

“…The response time is less than thalidomide alone, the duration of the response is greater and the EFS is better despite the OS being similar between the two treatments. The most frequent adverse events in the two forms of treatment are neutropenia, anemia, thrombocytopenia, constipation, drowsiness and skin rash, but grade 3 and 4hematologic toxicity is higher with the use of thalidomide ( 72 ) (A).…”