Pharmion's thalidomide combo shows 76% response rate in myeloma study

By Angela McDaniels

Seattle, Dec. 13 - Pharmion Corp. said clinical data from multiple studies supports the combination of thalidomide with several other drugs as a treatment option for multiple myeloma.

A multi-center trial of 255 patients compared the efficacy and toxicity of the combination of oral melphalan and prednisone to melphalan and prednisone plus thalidomide in newly diagnosed multiple myeloma patients older than 65 years of age.

Patients treated with melphalan and prednisone plus thalidomide experienced overall response rates of 76%, versus 48% for melphalan and prednisone alone, and near-complete response rates of 28% versus 7%, respectively.

Melphalan and prednisone plus thalidomide patients also had better outcomes with regard to median progression-free survival (33 months versus 14 months) and two-year survival rates (82% versus 65%), the company said.

Looking at only those patients who completed the assigned six cycles in both study arms, the two-year survival rate was 90% for the melphalan and prednisone plus thalidomide arm versus 71% for patients given melphalan and prednisone.

Grade III/IV adverse events were reported in 49% of melphalan and prednisone plus thalidomide-treated patients versus 25% of those treated with melphalan and prednisone; they included thromboembolism, infections and peripheral neuropathy, the company said.

Data from a second multiple myeloma study in newly diagnosed elderly patients demonstrated differences in overall survival, response to treatment and progression-free survival.

Patients were given either melphalan and prednisone plus thalidomide, melphalan and prednisone or autologous stem cell transplantation (MEL100).

Analysis of data from 436 patients showed that, following a median follow-up time of 32.2 months, the progression-free survival time was significantly longer in the melphalan and prednisone plus thalidomide group (27.6 months), compared to the melphalan and prednisone patient group (17.1 months), the company said.

No significant difference was seen between the melphalan/prednisone and MEL100 groups.

Based on the results, enrollment was stopped after this analysis. The investigators concluded, based on this data, that the reference treatment for newly diagnosed multiple myeloma patients, ineligible for high-dose therapy, should be melphalan and prednisone plus thalidomide, the company said.

"In both of these trials, the addition of thalidomide to the standard melphalan-prednisone regimen represents a significant clinical benefit to elderly, newly diagnosed multiple myeloma patients," said lead investigator Antonio Palumbo of Universita di Torino, Italy, in a company news release.

"These data suggest that thalidomide, which is widely used in relapsed/refractory myeloma, may serve a promising role in first-line therapy as well."

Thalidomide-dexamethasone

An interim analysis of a study of 125 previously untreated elderly patients with multiple myeloma demonstrated an overall response rate of 67% for patients treated with thalidomide-dexamethasone versus patients treated with melphalan and prednisone (48%), the company said.

Analysis per protocol revealed an overall response rate of 89% in the thalidomide-dexamethasone arm and 66% in the melphalan and prednisone group.

Data from these patients demonstrate a significantly shorter time to response and time to best response in the thalidomide-dexamethasone group (eight weeks and 11 weeks) as compared to the melphalan and prednisone group (10 and 39 weeks).

Additionally, grade III/IV thrombocytopenia was more frequent and leucopenia was more statistically significantly more common in the melphalan and prednisone group, the company said.

Thalidomide plus melphalan

Data from a prospective, randomized study of 668 patients examining the impact of adding thalidomide to melphalan-based tandem autotransplants for multiple myeloma found that, while the addition of thalidomide did not significantly extend overall survival, it did significantly increase complete response rates

The response rate for thalidomide plus melphalan was 59%; for melphalan alone, 41%, the company said.

In addition, patients receiving thalidomide plus melphalan demonstrated improved five-year event-free survival rates of 54%, versus 42% for melphalan alone.

Thalidomide with chemotherpay and stem cell transplant

Interim data from 593 patients in a study assessing the role of thalidomide maintenance therapy among multiple myeloma patients receiving high-dose chemotherapy and autologous stem cell transplant found the four-year, post-diagnosis probability of event-free survival was highest for patients receiving thalidomide, the company said.

In the study, patients received two autologous transplants with melphalan doses of 140mg/m2 and 200mg/m2, respectively. Those without progressive disease after two months were randomized to receive no maintenance (arm A), pamidronate maintenance (arm B), or pamidronate maintenance with thalidomide (arm C).

At the time of this analysis, the four-year overall survival was similar for the three treatment groups; however, the data also demonstrate that the four-year post-diagnosis probability of event-free survival was 39% for patients in arm A, 37% in arm B and 50% for arm C.

"Following a single or double autologous transplant, nearly all multiple myeloma patients ultimately relapse," said lead investigator Michel Attal of the Hospital Purpan in Toulouse, France, in the release.

"This study demonstrates that the addition of thalidomide to this therapy may help manage residual disease and reduce the frequency of relapse."

The data was presented at the 47th American Society of Hematology Meeting in Atlanta.

Thalidomide is approved in Australia, New Zealand, Turkey and Israel for the treatment of multiple myeloma after the failure of standard therapies and the acute treatment of cutaneous manifestations of moderate to severe erythema nodosum leprosum, the company said.

Thalidomide is also indicated as maintenance therapy for prevention and suppression of the cutaneous manifestations of erythema nodosum leprosum recurrence.

Multiple myeloma is a cancer of the blood in which malignant plasma cells are overproduced in the bone marrow. Multiple myeloma cells can also attach to other tissues of the body, such as bone, and produce tumors.

Pharmion is a pharmaceutical company based Boulder, Colo., that develops products for the treatment of hematology and oncology patients.

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