Thalomid in Multiple Myeloma: No Survival Advantage

For people with multiple myeloma, adding Thalomid (thalidomide) may improve complete responses and event-free outcomes but does not improve overall five-year survival, according to a new study.

Results of the study by Bart Barlogie, MD, PhD, of the University of Arkansas, and colleagues were published in The New England Journal of Medicine and reported by MedPage Today on March 9, 2006.

Clinical Trial

Dr Barlogie and colleagues studied 668 people with newly diagnosed multiple myeloma. All study participants received intensive Alkeran (melphalan)-based chemotherapy in two cycles along with autologous hematopoietic stem-cell transplantation.

Of the 668 participants, approximately half (323) were randomly assigned also to receive Thalomid; the other 345 participants were controls (i.e, did not receive Thalomid).

The median follow-up time among survivors was 42 months, at which pint the participants receiving Thalomid had a complete response rate of 62%, versus 43% for the control group. The five-year event-free survival rates were 56% and 43%, respectively. However, despite the Thalomid group's superior event-free survival rate, the overall five-year survival rate was approximately 65% in both groups.

The researchers ascribed the similarity in overall five-year survival between the two groups to the Thalomid group's significantly shorter median survival-rates after relapse (1.1 years, versus 2.7 years in the control group).

Another factor affecting results was that, among participants receiving Thalomid, severe peripheral neuropathy and deep-vein thrombosis occurred more often (e.g., deep-vein thrombosis initially occurred in 34% of the first 162 participants receiving Thalomid, versus only 18% of the first 174 in the control group). These events prompted dose-changes in many participants, particularly the elderly ones.

Additionally, relapses among participants receiving Thalomid appeared to be more drug-resistant than relapses in the control group. The shorter overall survival rates may also be explained by the higher failure-rate with salvage-therapy and shorter survival after relapse.

"Our results indicate that a complete response is not a valid surrogate for survival in myeloma clinical trials," Dr Barlogie and colleagues wrote. "When incorporated into high-dose therapy for myeloma, thalidomide increased the frequency of complete responses and extended event-free survival at the expense of added adverse effects without improving overall survival."

Editorial Commentary

In an editorial published in the same issue, Michele Cavo, MD, and Michele Baccarani, MD, of the University of Bologna in Italy, commented that participants' higher failure-rate in responding to salvage-therapy, and the dose- and duration-related toxicity of Thalomid, require further investigation.

They went on to note that the recent addition of newer drugs means that, "The landscape of myeloma treatment has changed substantially over the past few years. New agents have moved rapidly from the bench to the bedside, and they are important additions to the treatments now available for myeloma."

The continue, "Currently, the main clinical challenges are determining the optimal dose of new agents, whether they should be given sequentially or in combination, and how they should be integrated with old therapies," noting that there are two basic treatment strategies:

The first aims to eradicate the tumor using a combination of most or all available agents and high-dose therapy with stem-cell transplantation. However, they note, "Whether such an approach can modify the course of myeloma is uncertain, as reflected in the study by Barlogie et al."

The second approach is somewhat more conservative, reserving use of new agents for sequential treatment of relapses, as a means of controlling tumor growth or regrowth, "thereby converting myeloma into an indolent disease."

"Through biologic and clinical research in myeloma, we are uncovering effective new treatments that promise long-term benefit to a substantial proportion of patients with a cancer for which palliation was a reasonable goal even as recently as a decade ago," they conclude.

Source: No Survival Advantage for Thalomid in Multiple Myeloma, MedPage Today, March 9, 2006. Thalidomide and Hematopoietic-Cell Transplantation for Multiple Myeloma. Bart Barlogie et al, New England Journal of Medicine, volume 353, pages 1021-1030, 2006. Baccarani, Michele, The Changing Landscape of Myeloma Therapy. Michele Cavo, New England Journal of Medicine, volume 353, pages 1076-1078, 2006.

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