Newly diagnosed, high-risk multiple myeloma patients can be effectively treated with sequential therapy, according to the results of a recent Phase 2 study.  Participants in this study initially received a combination of Velcade, Doxil, and dexamethasone followed by a combination of thalidomide and dexamethasone, with the potential addition of Velcade to the second phase.

The study authors found that the sequential treatment provided rapid responses, which they said is crucial for patients with organ damage or those with advanced disease who need to quickly proceed to stem cell transplantation.

They suggested that clinical trials should be performed to further assess the effectiveness and side effects of combination therapies, including studies to determine how many drugs should be used simultaneously and also to compare combination therapies taken at the same time versus sequentially.

Previous studies have shown that the combination regimen Velcade (bortezomib), Doxil (doxorubicin liposomal), plus dexamethasone (Decadron) (abbreviated as VDD) is effective as initial therapy for newly diagnosed myeloma patients, elderly patients, and those undergoing a stem cell transplant.

The study authors, who are from the Memorial Sloan-Kettering Cancer Center in New York, have previously reported that treatment using dexamethasone and doxorubicin immediately followed by thalidomide (Thalomid) and dexamethasone (abbreviated as TD) results in good responses for newly diagnosed myeloma patients. However, survival was shorter for patients with high-risk myeloma.

Therefore, the authors wanted to study the effectiveness of sequential VDD therapy and TD or Velcade plus TD (abbreviated as VTD) treatment in high-risk myeloma patients.

The study included 42 newly diagnosed high-risk myeloma patients.  All had stage 2 or 3 disease or myeloma that developed outside of the bone marrow; additionally, 32 percent had high-risk chromosomal abnormalities. The median age of the patient group was 58 years.

Patients were first treated with three cycles of VDD.  Patients who achieved at least a partial response to VDD then received two cycles of TD.  Patients who did not achieve a partial response after the initial therapy received a more aggressive treatment of Velcade, thalidomide, and dexamethasone (abbreviated as VTD).

After VDD treatment, the overall response rate was 81 percent; specifically, 26 percent of patients achieved a near complete or complete response, 14 percent achieved a very good partial response, and 41 percent achieved a partial response.

After the initial therapy, 60 percent of patients received TD therapy, 10 percent received VTD therapy, 14 percent proceeded to stem cell transplant, and the rest discontinued therapy.

Continuation of therapy did not significantly increase the response rate (83 percent); however, many patients achieved deeper responses.  Specifically, 43 percent achieved a near complete or complete response, 17 percent achieved a very good partial response, and 23 percent achieved a partial response.

Among the study participants, 81 percent tried to collect stem cells and all were able to collect enough for transplantation. Of the patients who underwent transplantation, the overall response rate was 97 percent; specifically, 70 percent achieved a near complete or complete response, 17 percent achieved a very good partial response, and 10 percent achieved a partial response.

The overall survival rate was 88 percent after one year and 83 percent after two years. Patients who achieved at least a partial response had a higher overall survival rate than those who did not achieve a partial response. Additionally, the chromosomal abnormalities del(13q) and t(4;14) were associated with poorer survival (50 percent after one year); however, the researchers cautioned that the number of patients with these abnormalities was small.

The most common side effects were fatigue (43 percent), constipation (36 percent), sensory (29 percent) or painful (19 percent) neuropathy (pain and tingling sensations in the extremities), infection (28 percent), and low blood cell counts (24 percent low red blood cell counts, 24 percent low platelet counts, and 10 percent low white blood cell counts). According to the researchers, the blood-related side effects were manageable.

In total, 31 percent of patients did not complete treatment due to side effects.  The authors noted that this discontinuation rate is high and may in part be due to the use of high-dose dexamethasone during the TD or VTD phase of the treatment.

For more information, please see the study in Leukemia and Lymphoma (abstract).