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

Novel agents and proteasome inhibitors in myeloma

Professor Michele Cavo – University of Bologna, Italy


I think that probably the most exciting results are related to a growing number of novel agents which are knocking at the door and which will be available within the next few years. We have now second or third generation IMiDs and proteasome inhibitors, several of them are very promising because both third and second generation IMiDs and proteasome inhibitors are able to overcome resistance to bortezomib or lenalidomide. Another important issue related to second generation proteasome inhibitors such as carfilzomib is that, differently from bortezomib, it avoids neurological toxicity which is one of the major concerns related to bortezomib administration.

Pomalidomide is another example of a very active drug but a lot of other abstracts are also creating interest. For example, it will be presented the results of a large trial comparing bortezomib with bortezomib and a histone deacetylase inhibitor or, for example, preliminary data on an oral proteasome inhibitor which makes a big difference in comparison with the other first or second generation proteasome inhibitors which are given intravenously or sub-cue. So I think that the landscape of myeloma therapy is progressively expanding and that new options can be really offered to our patients.

Over the past decade the treatment paradigm for transplant eligible and non-transplant eligible has been dramatically changed by the introduction of novel agents. Novel agents, for example incorporated into autologous stem cell transplantation as part of induction before transplant and as consolidation in maintenance therapy after transplant, have dramatically improved the clinical outcome of these patients who now are able to achieve not only conventionally defined complete response in a substantially high fraction of patients but also to obtain the deepest level of response up to the molecular level, as detected by molecular techniques in more than 50% of patients. These results are unprecedented so this shows how the novel agents have dramatically changed the treatment paradigm for myeloma patients. And also for patients with relapsed refractory disease the landscape is progressively changing and we now are able to offer new effective drugs to patients who develop resistance to bortezomib and lenalidomide and our expectation, due to the growing number of patients who will receive these novel agents as first line therapy, is that in the next future the management of patients with dual refractoriness to bortezomib and lenalidomide will become an unmet medical need. Hopefully we have now several promising agents which, as a single drug, show the possibility to overcome resistance in approximately one third of these patients. So I think that we can have a message of real hope for our myeloma patients.