I was tasked with talking about whether the treatments in treating multiple myeloma whether less is more. In many of the hematologic malignancies with advances in treatment the treatments are more tolerable with better side effect profiles and more effective so the former model of more aggressive therapy resulting in better outcomes for our patients may not necessarily hold true. So in my talk here at SIOG I have been focussing on the studies which have indicated that a more aggressive approach does not benefit our patients. Conversely there are some studies that show that more aggressive treatment or longer duration of therapy or maintained dose intensity do benefit our treatment.
What will be the types of changes to doses and regimens?
The literature varies depending on the toxicity of the treatment. For example, in a study known as the UPFRONT study with the first author Niesvizky from JCO in 2015, in a randomised trial they demonstrated that there were similar response rates, progression free and overall survival, whether the patients received bortezomib and dexamethasone alone or in combination with melphalan or in combination with thalidomide. So in that case patients treated with bortezomib and dexamethasone alone didn’t benefit from the addition of an additional agent. Conversely, in the FIRST trial published by Benboubker in the New England Journal in 2014, patients who were treated with lenalidomide and dexamethasone continuously had better overall survival, progression free survival, than patients treated with a finite duration of lenalidomide and dexamethasone truncated at about 18 months or with melphalan, prednisone and thalidomide truncated at 18 months. So patients treated continuously with a very tolerable regimen had an overall survival benefit.
Do you see this informing the next set of SIOG guidelines?
Absolutely, attention to the balance between efficacy and tolerance of therapy are going to be the real hallmark of treatment of multiple myeloma. The FIRST trial, for example, will be a very, very important trial in demonstrating the importance of continuous rather than interrupted therapy.
How might emerging therapies, such as immunotherapy, change this?
A very good question. The role for immunotherapy in the setting of multiple myeloma is still evolving. Nivolumab was shown to have no single agent activity but there is a lot of interest in seeing how the immunotherapeutic agents will work in concert with our existing platforms such as the immunomodulatory agents. There’s going to be a lot of interest and hope for that, the combination, as opposed to the single agent activity. In addition, the new generations of medications including daratumumab which was studied in the CASTOR and POLLUX trial did look at subgroup analysis for whether there was an interaction with age and across all the newest studies, including the CASTOR, POLLUX and EVOLUTION trial and so on, they have demonstrated that the older adults in those clinical trials benefitted to the same degree that younger adults benefitted in those studies. We have to keep in mind, though, that the inclusion criteria for clinical trials often are really tailored towards the fittest of the fit older adults so ultimately we’ll want to replicate those findings in more vulnerable populations demonstrating their efficacy while maintaining a good safety tolerability profile in our older adults with multiple myeloma.