The results of a recent British analysis found that multiple myeloma patients with a deletion in chromosome 17 who received thalidomide induction therapy had improved response rates compared to those who did not receive thalidomide. 

These improved response rates also were accompanied by improve­ments in patients' overall survival, but the improvements were not statistically significant.

Moreover, patients with a deletion in chromosome 17 who received thalidomide as part of a maintenance regimen had shorter overall survival than those who did not receive thalidomide maintenance.

Based on these findings, the study authors conclude that alternative therapeutic strategies may be needed for patients with a deletion in chromosome 17 (abbreviated "del(17p)").

Chromosomal abnormalities, which result from the deletion, insertion, duplication, or swapping of chromo­somal segments, may render patients less responsive to certain treatments. 

In particular, it has been shown that, in relapsed/refractory myeloma patients with del(17p), combination therapy with Revlimid ^[1] (lenalidomide) and dexamethasone ^[2] (Decadron) results in decreased time to disease progression and decreased overall survival (see related Beacon ^[3] news).

Although there have been many studies investigating the effect of older, "conventional" myeloma therapies on the outcome of patients with chromosomal abnormalities, there is currently little data available about how these abnormalities affect outcomes in patients treated with the novel agents thalidomide ^[4] (Thalomid), Revlimid, or Velcade ^[5] (bortezomib).

In their study, the British researchers sought to further assess the effect of thalidomide-based therapies on patients with del(17p).

The researchers retrospectively analyzed data for patients with del(17p) who had participated in the MRC Myeloma IX trial. 

The Myeloma IX trial involved almost 2000 newly diagnosed multiple myeloma patients, mostly in the United Kingdom.  It was designed to compare the efficacy of the bisphosphonates Zometa ^[6] (zoledronic acid) and Bonefos ^[7] (clodronic acid) in myeloma patients (see related Beacon ^[8] news) while also investigating the efficacy and safety of several different myeloma treatment regimens.

Among all the patients participating in the Myeloma IX trial, 85 were identified who had del(17p).  Of those 85 patients, 54 percent received a thalidomide-based induction therapy and 46 percent received conventional induction therapies that did not include thalidomide or any other novel agent.

The authors of the current study found that patients with del(17p) who received thalidomide-based induction therapy had an improved overall response rate of 92 percent compared to 72 percent for patients whose induction therapy did not include thalidomide.  In particular, 21 percent of patients receiving thalidomide achieved a complete response, compared to 6 percent of patients who received conventional induction therapies.

Small improvements were also observed in the median progression-free survival times of patients receiving thalidomide, which was 15.5 months compared to 12.2 months for those given conventional induction therapy.

These improvements also were reflected in median overall survival times, which were 28 months for patients receiving thalidomide and 23.5 months for conventionally treated patients.  However, these im­prove­ments in overall survival were not statistically significant.

In addition, the researchers found that thalidomide had negative effects in del(17p) patients when adminis­tered as part of a maintenance therapy regimen. 

Half the patients in the Myeloma IX trial were randomly selected to receive maintenance treatment with thalidomide.  The other half of the patients received no maintenance therapy.  Patients who received thalidomide maintenance therapy did not necessarily receive thalidomide as part of their induction therapy.  The selection of patients for maintenance therapy was made without consideration of the patient's induction therapy.

Among the 11 patients with del(17p) who did not receive thalidomide maintenance therapy, median overall survival has not yet been reached at a follow-up time of more than 50 months.  In comparison, median overall survival was 23.6 months for the 17 patients with del(17p) who received thalidomide maintenance therapy.

The British researchers believe, however, that two factors may explain the difference in survival between the maintenance and no-maintenance groups of patients.

The rate of other high-risk chromosomal abnormalities was higher in patients receiving thalidomide maintenance therapy. In addition, many of the patients on thalidomide maintenance continued thalidomide therapy after relapse, which, according to the study authors, is not the most effective treatment in that situation.

For additional information, please see the study in the journal Leukemia ^[9] (abstract).