During the meeting in Chicago, Dr. Palumbo described what he saw as the highlights of the ASCO conference regarding multiple myeloma, and discussed them with the IMF:
DR. PALUMBO: I mainly saw an update of data from the French (IFM) trial showing that the combination of VELCADE® plus dexamethasone in comparison to VAD...is increasing the response rate before and after autologous transplant. From this point of view, I agree with Jean-Luc Harousseau that this combination is becoming a standard of care as induction treatment before autologous transplant.
The other major issue was an update coming from Vincent Rajkumar (E4A03 ECOG) that the combination of REVLIMID® and dexamethasone is consistently showing a treatment schedule with a very good safety profile that is effective in a wide population of myeloma patients, and is consistently showing a survival advantage.
IMF: The presentations almost look mutually exclusive. Dr Harousseau is saying VELCADE-dexamethasone, Dr. Rajkumar is saying REVLIMID-dexamethasone. What's a patient to do?
DR. PALUMBO: Well, the point is we don't know yet. The point is these represent at present the two major treatment paradigms for myeloma where to some extent you have the REVLIMID approach, which is an easy approach—very few toxicities, very well tolerated, oral treatment, like a (chronic) hypertension treatment. Very, very nice approach in terms of quality of life and safety profile.
On the other hand, you see, let's say the "intensive treatment" where you try to get as much CR (complete response) as you can, paying a price in terms of autologous transplant, in terms of higher toxicity rate. The question is, if the higher toxicity is the right price to pay to get a better outcome, and I think this is an open question at present...
IMF: What else was important at the conference?
Dr. Palumbo noted the presentation by Dr. Bart Barlogie (University of Arkansas for Medical Sciences [UAMS]) saying that he showed" impressive results," but adding that they are not randomized studies so to some extent they are limited by the fact they do not have a control arm.
Dr. Palumbo went on to discuss what he sees as potential new paradigms of treatment:
DR. PALUMBO: We are now used to combinations of new drugs plus dexamethasone. Now what is coming is if you combine new drugs with some other chemotherapy adjunct, such as doxorubicin or cyclophosphamide, you can significantly increase the response rate in comparison to (regimens) including new drug plus dexamethasone only.
So this is the new paradigm that is coming.
The data are showing that if you use a chemotherapy adjunct instead of dexamethasone alone, significantly increases the response rate. How much this is important in terms of clinical benefit, needs again further studies.
At present we know bortezomib plus cyclophosphamide is better that bortezomib and dexamethasone. Again I showed the bortezomib-doxorubicin is better than again, bortezomib and dexamethasone, but we just have response rate results and we need progression free survival, and eventually we need survival results in order to make a definitive statement.
Drugs in combinations and sequence
Then, I would say there is the data I presented that to some extent may represent a new treatment paradigm, because the data I presented included bortezomib-doxorubicin-dexamethasone as induction treatment, followed by autologous transplant, followed by lenalidomide as consolidation and maintenance approach.
So this is a different paradigm, where you use VELCADE that is a fast inducing-response drug and you use it as induction, and then you use REVLIMID as maintenance. And probably this, in my opinion, is the best way to use those drugs, because VELCADE is a fast inducer of response, REVLIMID is very well tolerated for a long term approach such as consolidation in combination with corticosteroids and eventually maintenance with REVLIMID alone.
Our result, though just preliminary, just a phase II study, shows very high response rate with a CR rate of 57% and a very good partial response rate (VGPR) of 88%. These are quite encouraging results and they probably deserve further study to evaluate this new type of approach, which is not a combo approach, it's a sequential approach.
Then last but not least, there is the other paradigm coming from the Dana Farber Institute, mainly showing the combo of VELCADE and REVLIMID together, and again showing if you combine those two drugs you have a very high proportion of response with to some extent limited toxicities. This is the other paradigm, to use those drugs in combination instead of the sequential approach I choose, and this is definitely the other approach that deserves further studies in the future because it could become an important standard of care.
All those data are at present preliminary, so I wouldn't say there is something conclusive, but I think the idea is that we open a new window and now we have to figure out how those new windows are really creating new standards of care.
IMF: What's going to happen from here?
DR. PALUMBO: What's going to happen is basically all the options are on the table. We have to figure out in controlled trials which is really the good one and which is the real option that we can translate into a significant clinical benefit. That's the new idea.
We already have those new drugs. We now know that they're working. What we need to do now is fine tuning. And the fine tuning is to modulate the dose, to see which is the best combo, to understand which is the best combo for the induction, which is the best combo for consolidation, which is the best combo for maintenance.
So, to some extent if you want to know my personal opinion, but it is just a personal opinion, I would say at the present the best treatment is for the younger patient still a combination using VELCADE as induction, followed by autologous transplant, and personally, if you do not reach a CR I see maintenance and consolidation with REVLIMID. And on the other hand with the elderly patient I am much, much more in favor of REVLIMID plus dexamethasone, or REVLIMID plus dexamethasone plus an alkylating agent, which I believe is important in the induction treatment, at least according to the European perspective, and should be considered a standard of care.
IMF: You mentioned transplant. What's the role of transplant now in light of these new data, because Dr. Rajkumar's data—landmark analysis&mdashshowed the same outcome with transplant and REVLIMID/dexamethasone
DR. PALUMBO:I'm in favor of the "Rajkumar option" because to some extent—before I make a final statement I do want to see a randomized trial, but if I just have to give my impression—I strongly believe conventional treatment could be equal to autologous transplant, or to some extent a little bit less effective, but it shouldn't be an important difference.
This is in my opinion the expectation, because I don't see a major difference between the conventional treatment with new drugs versus autologous transplant.
IMF: But it's still too soon to make that a definitive statement?
DR. PALUMBO: We need controlled studies to make a definitive statement.