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2013 Top Stories in Oncology: Myeloma
RubenNiesvizkyMD
PracticeUpdate: In your view, what developments that occurred in 2013 in myeloma research could have the most significant impact on clinical practice?
Dr. Niesvizky: Pomalidomide is one of the most important stories in 2013. It is the newest of all the immunomodulators developed and has been approved for use in relapsed/refractory multiple myeloma. It was great to hear at ASH that now individuals who have the worst prognosis actually benefit significantly with the use of pomalidomide.
Pomalidomide, as a single agent, was presented at ASH Dr. Dimopoulos in the follow-up of the approval study.1 However, two other studies are relevant, which have shown increased response rates and increased progression-free survival.
One study from our group2 showed that the addition of the antibiotic clarithromycin has increased the response rates to over 58%, even in the double refractory setting and high-risk myeloma. It is very gratifying that you can improve the life expectancy and the survival of these types of patients.
The other interesting study presented was a combination of carfilzomib, pomalidomide, and dexamethasone,3 which increased a third of the response rates. So, it’s a combination that’s going to be widely used.
PracticeUpdate: How would you approach a patient with relapsed or refractory multiple myeloma at this point? What does the evidence suggest is the best therapy or the best approach?
Dr. Niesvizky: That’s a very difficult question because the situation is different for each patient. In other words, you’re going to have patients in earlier relapse, who require just a new drug; whereas, you have patients who have failed everything, and pomalidomide should be your potential drug in that group. So, I cannot tell you which one is the best regimen all around; but, certainly, the combination of pomalidomide and carfilzomib seems very attractive. The only problem with that combination is that it will be very expensive because they are both novel agents. Whereas the combination of pomalidomide and clarithromycin is oral and is much cheaper, which is why we are favoring it.
PracticeUpdate: Are there any other developments in myeloma in 2013 that you feel the practicing oncologists should be aware of?
Dr. Niesvizky: Certainly, the development of new monoclonal antibodies is important. One is called elotuzumab, and the other is daratumumab; there are others coming. One by Sanofi, SAR (SAR650984) appears to be a very effective single-agent with activity against relapsed/refractory multiple myeloma. This is the first time in years that an antibody actually has shown activity.
Elotuzumab has only shown activity when combined with lenalidomide and dexamethasone; it has no activity by itself, which is intriguing—why does it have no activity as a single agent, and, yet, when it’s combined with lenalidomide and dexamethasone it has such a tremendous activity? That’s why we are eager to see the results of the randomized trial of elotuzumab.
On the other hand, there are the CD38 antibiotics, of which there are now three. One is the daratumumab, in a study run by J&J, one is run by Sanofi, and then there’s a third one by Celgene. The three of them appear to be very exciting molecules that may exhibit single-agent activity. It’s not only that now we have an antibody, but we also have single-agent activity. They are being studied in combination with immunomodulatory drugs, steroids, and with proteasome inhibitors, and they all appear to be very well-tolerated.
PracticeUpdate: Would you sum up how you view the clinical developments this year in the treatment of myeloma?
Dr. Niesvizky: I would say the development of very effective induction regimens all surpassing 90% overall response rate or reaching more than 50% complete responses. The next step will be to develop surrogate markers in terms of minimal residual disease to see which one of these combinations give the best results, and how they translate in long-term survival. We are waiting for next year to see what the role of transplant will be in all these patients as we have better drugs.
In terms of maintenance, there is a general consensus that long-term therapy is superior to limited therapy in the elderly, but that still needs to be proven in the transplant setting; whereas, there is conflicting evidence whether maintenance therapy is indeed necessary.
Finally, in the relapsed/refractory setting, the new drugs, particularly the newer proteasome inhibitors, including the orals, the new immunomodulators, and, more importantly, the monoclonal antibodies are bringing a lot of promise in myeloma.
Hope the info helps, Carm
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December 2013