ASH: Thalidomide benefit to elderly patients

Pharmion Corporation (Nasdaq: PHRM) reported today on data abstracts from studies investigating the role of thalidomide as a treatment option for all stages of multiple myeloma. Results of these and numerous other thalidomide studies were presented at the American Society of Hematology Annual Meeting (December 10-13, 2005).

An analysis of data from a multi-center trial of 255 patients comparing the efficacy and toxicity of the combination of oral melphalan and prednisone (MP) to MP plus thalidomide (MPT) in newly diagnosed multiple myeloma (MM) patients older than 65 years of age was presented. Patients treated with MPT experienced overall response rates of 76 percent vs. 48 percent for MP alone, and near- complete response rates of 28 percent vs. 7 percent, respectively. MPT patients also had better outcomes with regard to median progression-free survival (33 months vs. 14 months), and two-year survival rates (82 percent vs. 65 percent). Looking at only those patients who completed the assigned six cycles in both study arms, the two-year survival rate was 90 percent for the MPT arm vs. 71 percent for patients given MP, a statistically significant difference. Grade III/IV adverse events were reported in 49 percent of MPT-treated patients vs. 25 percent of those treated with MP; they included thromboembolism, infections and peripheral neuropathy.

Data from a second multiple myeloma study in newly-diagnosed elderly patients demonstrated differences in overall survival, response to treatment and progression-free survival (PFS). Patients aged 65-75 were given either MPT, MP or autologous stem cell transplantation (MEL100). The study compared MPT vs. MP, MP vs. MEL100, and MPT vs. MEL100. Analysis of data from 436 patients, 191, 124 and 121 in MP, MPT and MEL100 groups, respectively, showed that following a median follow-up time of 32.2 months, the PFS time was significantly longer in the MPT as compared to the MP patient group (27.6 months for MPT and 17.1 for MP. No significant difference was seen between the MP and MEL100 groups. Based on the superior results for the MPT arm, enrollment was stopped after this analysis. The investigators conclude, based on this data, that the reference treatment for newly diagnosed multiple myeloma patients, ineligible for high-dose therapy, should be MPT.

Study Assesses Thalidomide Combination Therapy in Newly Diagnosed Patients (abstract 782)

An interim analysis of response rates from a study of previously-untreated elderly patients with multiple myeloma was presented in an oral session on Tuesday, December 13. A total of 125 evaluable patients, randomized to receive either thalidomide-dexamethasone (TD) or melphalan-prednisone (MP), demonstrated a overall response rate (ORR) of 67 percent for the TD arm vs. 48 percent on MP. Analysis per protocol revealed an ORR of 89 percent in the TD arm and 66 percent in the MP group. Data from these patients demonstrate a significantly shorter time to response and time to best response in the TD group as compared to the MP group (8 and 11 weeks for TD vs. 10 and 39 weeks for MP). Grade III/IV thrombocytopenia was more frequent and leucopenia was more statistically significantly more common in the MP group.

Data Highlight Results from Total Therapy 2 Trial in First Line MM Patients (abstract 423)

Data from a prospective, randomized study of 668 patients were presented in an oral session on Monday, December 12. This study examined the impact of adding thalidomide (T) to melphalan (MEL200)-based tandem autotransplants for multiple myeloma. While the addition of thalidomide did not significantly extend overall survival, potentially due to an imbalance of cytogenetic changes between the two arms, it did significantly increase complete response rates (41 percent with MEL200 alone vs. 59 percent with MEL200 plus T). In addition, patients receiving thalidomide with MEL200 demonstrated improved five-year event-free survival rates (42 percent for MEL200 vs. 54 percent for MEL200 plus T).

Data Assess Impact of Thalidomide Maintenance Therapy Following Autologous Transplantation in Multiple Myeloma (abstract 1148; poster session 306-I)

Interim data from 593 patients (under age 65) in a study assessing the role of thalidomide maintenance therapy among multiple myeloma patients receiving high-dose chemotherapy and autologous stem cell transplant were presented in a poster session on Saturday, December 10. In the study, designed to examine duration of response after high-dose VAD therapy, 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 percent for patients in arm A, 37 percent in arm B and 50 percent for arm C. The benefit was particularly pronounced among patients with a beta-2-microglobulin >2.5mg/l without deletion of chromosome 13.

"Following a single or double autologous transplant, nearly all multiple myeloma patients ultimately relapse," said Pr Michel Attal, MD, lead investigator, Service d'Hematologie, Hopital Purpan, Toulouse, France. "This study demonstrates that the addition of thalidomide to this therapy may help manage residual disease and reduce the frequency of relapse."

Source: http://www.pharmion.com