Results of a recent Phase 2 study indicate that a steroid-free regimen of Velcade, Doxil, and thalidomide is effective in newly diagnosed multiple myeloma patients.

“The most novel aspect [of the study] is that high response rates and effective disease control can be achieved without the use of [the corticosteroid] dexamethasone,” said Dr. Asher Chanan-Khan, one of the study’s investigators and a researcher at the Roswell Park Cancer Institute in Buffalo, New York.

“The development of such a regimen is critical as it can be used both in newly diagnosed or relapsed patients [in whom] steroid-associated toxicity is a major concern,” he added.

Dr. Rafael Fonseca from the Mayo Clinic in Arizona, who was not involved in the study, described the combination as a very impressive and active combination.  “It further supports the role of combinatorial therapy for front-line therapy of the disease,” he said.

The study authors, however, recommended further evaluation of this three-drug combination in Phase 3 studies involving a larger patient population. 

When administered in high doses, corticosteroids such as dexamethasone (Decadron) and prednisone have been shown to improve treatment outcomes for myeloma patients treated with novel agents such as Velcade (bortezomib), thalidomide (Thalomid), and Revlimid (lenalidomide). As a result, they are a standard part of first-line regimens for treating myeloma.

According to Dr. Fonseca, most patients can tolerate dexamethasone, especially since physicians have started administering the drug at 40 mg once per week.  

However, steroids are poorly tolerated in some elderly myeloma patients, especially those who have additional disorders such as diabetes or heart disease.

High doses of steroids can also increase the risk of infection for patients and ultimately compromise their treatment outcomes.

“While initially dexamethasone can help achieve high response rates, studies have demonstrated that high doses can actually be harmful and may compromise survival outcome,” explained Dr. Chanan-Khan.

In order to maximize treatment outcomes for myeloma patients who are unable to tolerate steroid-related side effects, researchers in recent years have been investigating the efficacy of different steroid-free drug combinations.

Results of a previous Phase 2 study, for instance, showed that a combination of Velcade and thalidomide without steroids is effective in newly diagnosed myeloma patients (see related Beacon news).

A separate Phase 3 study further suggested that a steroid-free combination of Velcade and Doxil (liposomal doxorubicin) increased the progression-free survival time of myeloma patients compared to Velcade alone.  

In this study, the authors investigated the efficacy of Velcade-Doxil-thalidomide, known as VDT, in newly diagnosed myeloma patients.

The study included 40 newly diagnosed multiple myeloma patients with a median age of 60.5 years.

All patients received six 28-day cycles of initial therapy with 1.3 mg/m² of Velcade on days 1, 4, 15, and 18; 20 mg/m² of Doxil on days 1 and 15; and 200 mg of thalidomide daily.

Patients who had residual disease after six treatment cycles and who responded to treatment could receive two additional cycles.

After completing treatment, all patients were followed up every three months until progression, relapse, or start of subsequent therapy.

The overall response rate was 78 percent, with 23 percent of patients achieving a complete response.

The median time to best response for patients who achieved a complete response was 7.4 months.

The median time to progression was 29.5 months.

According to Dr. Chanan-Khan, overall survival rates were not reported because the study’s purpose was to evaluate the treatment’s efficacy after induction.

The most common non-blood-related side effects were mild and included rash (67 percent), fatigue (63 percent), and constipation (63 percent).

The most common blood-related side effect was low white blood cell counts (66 percent). Fifty-three percent of patients experienced manageable cases of peripheral neuropathy characterized by pain and tingling sensations in the extremities.

According to the study authors, patients had a high risk of infection and should receive preventive antibiotics during their initial therapy in further studies. 

There were no treatment-related deaths. One patient died from disease progression.

For more information, please see the article in the British Journal of Haematology (abstract).