GIMEMA study compares bortezomib-thalidomide-dexamethasone with thalidomide-dexamethasone prior to double autologous stem-cell transplantation

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Published: 13 Dec 2011
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Prof Michele Cavo - University of Bologna, Italy

Meeting with ecancertv, Prof Cavo, an investigator on the GIMEMA Italian Myeloma Network designed trial presented during ASH 2011, speaks to ecancer.tv about its findings.

 

In the phase 3 trial comparing thalidomide-dexamethasone (TD) with bortezomib- thalidomide-dexamethasone (VTD) as induction therapy prior to and consolidation therapy after double autologous stem-cell transplantation for previously untreated multiple myeloma patients, the VTD arm was significantly superior over TD in terms of improved rates of complete or near-complete response and progression free survival. Toxicity of VTD and TD regimens, including peripheral neuropathy, was a secondary study endpoint.

 

The abstract can be viewed on the ASH website here.

 

This programme has been supported by an unrestricted educational grant from Janssen Pharmaceutica (A Johnson & Johnson Company).

2011 ASH Annual Meeting, December 10-13, San Diego, USA


GIMEMA study compares bortezomib-thalidomide-dexamethasone with thalidomide-dexamethasone prior to double autologous stem cell transplantation

 

Professor Michele Cavo – University of Bologna, Italy

 

We have several abstracts here at ASH, one of them is focussed on the frequency, reversibility and risk factors for patients who are treated with bortezomib and lenalidomide based induction regimens before transplant. And this was a sub-study within the GIMEMA trial which was aimed at comparing a combination of bortezomib with thalidomide and dexamethasone versus thalidomide and dexamethasone as induction before, and consolidation after, double autologous stem cell transplantation. So in this abstract we evaluated the frequency of peripheral neuropathy for patients exposed to bortezomib-thalidomide and those exposed to thalidomide with dexamethasone throughout the entire treatment programme. And the main results were that, in comparison with thalidomide-dexamethasone, the frequency of a grade 2 or higher peripheral neuropathy was three times higher with VTD; the rate of grade 3/4 was approximately 15% with VTD in comparison with approximately 3% for patients receiving thalidomide-dexamethasone. The great majority of patients who developed peripheral neuropathy had these adverse events during induction therapy, however, in almost 90% of patients in both the treated groups peripheral neuropathy resolved completely. So the message is that a short-term exposure to a combination of bortezomib-thalidomide or thalidomide alone does allow, to the great majority of patients, to receive the entire treatment programme.

 

We also looked at the baseline risk factors predicting for peripheral neuropathy and we were not able to find any relationship between patient and biological characteristics and the development of peripheral neuropathy. In a sub-study we also performed a gene expression profile of bone marrow plasma cells and we compared the molecular data between patients with grade 2 or higher peripheral neuropathy with the dose of patients who did not develop neurological toxicity. We were able to demonstrate that in patients with peripheral neuropathy there was a down-regulation of genes involvement in cytoskeletal rearrangement in neurogenesis and in axonal guidance.

 

The message is that apparently, and also consistently with the data, the frequency of grade 2 or higher peripheral neuropathy is higher when you combine bortezomib with thalidomide in comparison with thalidomide alone. However, if you look at the data from other studies in which bortezomib is given as a single agent in comparison with dexamethasone, the rate of grade 3/4 peripheral neuropathy is not higher using the combination of bortezomib-thalidomide. This means that the combination of two agents with neurological toxicity does not add anything to the expected rate of peripheral neuropathy with bortezomib as a single agent. And the second important message is that in the great majority of these patients neurological toxicity may reverse, provided that appropriate measures are taken, are given to the patients so that the patients ultimately are able to receive the entire treatment programme.