A recent study showed that maintenance therapy with thalidomide and interferon delayed progression, but did not extend survival, in elderly multiple myeloma patients. Additionally, the thalidomide-interferon maintenance therapy caused slightly more side effects than maintenance therapy with interferon alone.

Previous studies have indicated that in younger patients, maintenance therapy with thalidomide (Thalomid) after stem cell transplantation resulted in increased progression-free survival time in all trials and in increased overall survival time in two out of five trials (see related Beacon news 1, 2, and 3).

However, it was previously unclear how effective the thalidomide maintenance therapy was in elderly patients, many of whom are ineligible for stem cell transplantation.

This recent study, which was published in the journal Haematologica, assessed the efficacy and safety of maintenance therapy with thalidomide plus interferon alpha-2b in elderly myeloma patients who are transplant-ineligible. Researchers compared the results of the thalidomide-interferon maintenance therapy to the results of maintenance therapy with interferon alone.

The study enrolled 289 elderly myeloma patients who had been previously untreated and who were ineligible for stem cell transplantation. Half of the patients received induction therapy with thalidomide-dexamethasone (Decadron), known as TD, and the other half received melphalan (Alkeran)-prednisone therapy, know as MP. The 128 patients who completed all nine cycles of induction therapy went on to receive maintenance therapy with either thalidomide plus interferon or interferon alone.

The average progression-free survival time for patients who received thalidomide plus interferon maintenance therapy was 27.7 months, compared to 13.2 months for patients who were treated with interferon maintenance therapy only.

Patients who received thalidomide plus interferon maintenance therapy had similar progression-free survival times, regardless of the type of induction therapy (27.7 months for TD versus 27.6 months for MP).

Progression-free survival was somewhat shorter for patients who received MP induction followed by interferon maintenance therapy (20.2 months). However, patients who received TD induction therapy and interferon-only maintenance therapy experienced a significantly shorter progression-free survival time (7.8 months) than patients with other treatment combinations.

The average overall survival time was similar for both maintenance therapy groups.  For patients who received thalidomide plus interferon maintenance therapy, overall survival was 52.6 months, compared to 51.4 months for patients who were treated with interferon-only maintenance therapy. The overall survival time also did not vary significantly based on induction therapy. Additionally, there was no difference observed between patients who were younger than 75 years old and patients who were 75 or older.

At the time of publication, 48 patients involved in the study had died. Of these deaths, 23 were patients who received the thalidomide plus interferon maintenance therapy (with six deaths not related to myeloma), and 25 were patients who received the interferon maintenance group (with seven deaths not related to myeloma).

The patients who received the thalidomide plus interferon maintenance therapy experienced slightly more of the following side effects: neuropathy (tingling or numbness of the toes, fingers, feet, hands, or legs), constipation, skin rashes, impaired kidney function, fatigue, and shortness of breath. Three patients experienced blood clots (two with thalidomide plus interferon maintenance and one with interferon maintenance).

Based on this data, the authors of the study concluded that although there was a significant increase in progression-free survival in patients who received thalidomide plus interferon maintenance, compared to those who received only interferon maintenance, there was no difference in the overall survival between the two treatment groups. However, they acknowledge that it is difficult to fully analyze the overall survival data, since more than 60 percent of the study patients were still alive.

Additionally the authors wrote that the significantly shorter progression-free survival time experienced by patients who received TD induction therapy and interferon-only maintenance therapy suggests that “stopping thalidomide treatment after completion of a successful induction phase may result in earlier progression.”

The authors stated that due to the more frequent side effects associated with the thalidomide plus interferon maintenance therapy, there is only a “limited benefit” to elderly myeloma patients using this therapy instead of the interferon maintenance therapy. Additionally, they recommended for physicians to describe the “advantages, limitations, and potential [side effects]” of the thalidomide plus interferon maintenance therapy to patients in order for them to make a fully informed decision.

For more information, please read the full study in the journal Haematologica.