We know that triplet induction therapies for multiple myeloma are much more effective than doublet therapies and this has been proven time and time again in large phase III studies. What we don’t have is large studies prospectively to say that in an elderly transplant ineligible population what is the effect of a triplet induction therapy versus a doublet induction therapy? So what we set out to do is to use statistics and retrospective data to mimic a prospective trial.
The way that we did this is by using a propensity score analysis which is a statistical method to essentially create pseudo-randomised cohorts of two balanced cohorts of patients. We used US patients that were in a Medicare database and linked to the SEER database and balanced two cohorts, one who had received triplet induction therapy of Revlimid, Velcade and dexamethasone and the other half being a cohort that received the combination of either Revlimid and dexamethasone or Velcade and dexamethasone. We then used statistical methods to balance these cohorts and found that the patients who received three drugs, Revlimid, Velcade and dexamethasone, had a longer time to treatment failure or need to initiate another therapy or death as well as a longer overall survival as compared to those patients who received either doublet therapy of Revlimid dexamethasone or Velcade dexamethasone.
So we confirmed that triplet is better than doublet simply by using statistical methods with real world patients, if you will, not in a clinical trial. We then went on to say, ‘Okay, well we’ve never actually compared Revlimid and dexamethasone to Velcade and dexamethasone in a prospective trial.’ So we used the same methods to balance two cohorts, patients who received Revlimid and dexamethasone and those who received Velcade and dexamethasone and compared their time to treatment failure and overall survival and actually found somewhat surprisingly that the patients who received Revlimid and dexamethasone had a slightly longer time to treatment failure, or they were responding to therapy longer, and also had a slightly longer overall survival. Now this is outside the context of a prospective clinical trial but this is oftentimes the best we can do with what we have, knowing that a prospective clinical trial is not on the horizon.
We didn’t find any surprising toxicities in the patients who were included in the analysis, that the patients who received Revlimid had higher rates of thrombosis and the patients who received Velcade had higher rates of peripheral neuropathy, these are well-known potential side effects of the treatments.
Why is it important to focus on older patients?
Really because the average myeloma patient is somebody who is in their sixties and it’s very rare, only a couple of percent of patients are under the age of 40. The majority of myeloma patients are in their sixties or even older. So as life proceeds we know we can build different medical conditions that we have to take care of and, for us, when we’re sitting down across from somebody in a clinic how do we best assess that person and help them feel as good as they can for as long as they can? And oftentimes that’s an older patient.
What are the next steps?
Really the next steps are to expand the evaluation and to compare different induction regimens. So we’re working on comparing Velcade and dexamethasone to another triplet that has frequently been used in the US and around the world – CyBorD or cyclophosphamide, Velcade and dexamethasone. That’s coming up for ASH this year.