Multiple Strategies for the Treatment of Multiple Myeloma

Two significant presentations at this year’s ASH meeting may lead to changes in the standard of care in the treatment of multiple myeloma. The Intergroupe Francophone du Myelome (IFM) report results from an interim analysis of their IFM 9902 trial. In this study, presented by Dr. Michel Attal, eligible patients received VAD induction followed by tandem transplantation using high dose melphalan conditioning regimens. Patients were then randomized two months after the second transplant to one of three arms: Arm A – observation, Arm B –maintenance pamidronate, or Arm C – maintenance thalidomide plus pamidronate. One thousand and four myeloma patients were enrolled in this trial between 2000 and 2003, and, as of May 2004, 580 patients had been randomized. The groups were comparable for clinical characteristics. With a median follow-up of 26 months, the progression-free survival was significantly prolonged in the thalidomide group. At 40 months (from diagnosis) the probability of remaining progression free was 53 percent for Arm A, 52 percent for Arm B, and 70 percent for Arm C. No survival advantage has been seen, and this may never be demonstrated as 60 percent of patients in Arms A and B received thalidomide at progression.

The Eastern Cooperative Oncology Group reports updated data on a randomized phase III trial comparing thalidomide plus dexamethasone to dexamethasone alone. This report provides data on 198 of 202 eligible patients enrolled in the study. The primary endpoint was best response at four months. At that point, patients could elect to move on to autologous stem cell transplantation or continue with assigned protocol therapy. Slightly more than 100 patients were in each arm. The overall response rate was significantly higher in the thalidomide/dexamethasone arm compared to the dexamethasone arm (69 percent vs. 51 percent). Responses were equally rapid. There was more toxicity in the combination therapy arm. Grade 3 or higher non-hematologic toxicities occurred in 68 percent of the thalidomide/ dexamethasone patients compared to 43 percent of the dexamethasone patients. The presenting author, Dr. Vincent Rajkumar, concludes that the treatment decision must be individualized since the higher response rate is offset somewhat by an increased toxicity profile, but that either therapy could be viewed as a replacement for VAD induction.

Additional information on multiple myeloma was presented over the weekend at the Myeloma Education Session. Dr. John Shaughnessy described gene expression profiling data generated from patient samples. His group has identified four subgroups of patients whose GEP signatures are strongly correlated with cytogenetic abnormalities and clinical characteristics. Dr. Jean-Luc Harousseau reviewed the data supporting the use of autologous stem cell transplantation and discussed ways in which these results might be further improved. Dr. Paul Richardson focused on targeted therapy of myeloma. He discussed proteasome inhibition as well as newer targets such as the microenvironment, histones, and heat shock proteins. If you missed this session, a thorough summary is available in the ASH Education Program Book.