I know some of you are getting ready for transplant #2, so I thought I'd share some e-mail discussions I had in prep for my second transplant. I hope the information helps....it sure helped me. Best to all of you - Doug
Can you tell me if the Chemo Dr. Tricot uses for Transplant 2 is different from that used in Total Therapy III in Ark? If so, how is it different?
Yes, it is. From what I remember of Total Therapy III (and since I wasn’t the study coordinator for that protocol, my memory isn’t perfect regarding that trial), both transplants were Melphalan 200mg/m2 only. If you follow the protocol study schema for your second transplant, you will receive Velcade, Gemcitabine (aka Gemzar), BCNU, Melphalan, and Dex. So, it’s definitely a more intense cocktail than just Melphalan alone, but each additional drug serves an important purpose: Velcade and Dex aid in cytokine suppression post-transplant (cytokines are proteins produced in the body that regulate inflammatory responses, immunity, and blood cell division, and they can also stimulate MM cell production by producing growth factors for MM cells, so it’s important to squelch that cytokine storm that patients experience post-transplant.) Gemcitabine prevents DNA cell repair, which is one of the major mechanisms of Melphalan-resistance MM cells. And, BCNU is added because it will also kill MM cells with p53 alterations, which is seen in 10 to 15% of all myeloma patients and is associated with melphalan resistance and subsequent poor outcomes.
The conditioning Dr. Tricot is using now for the second transplant looks much like Total Theropy II <PR with the addition of Gemzar and the removal of the other two drugs. Is that right? It even looks as though he toned down the Mel from TT2. I'm curious why he went back to BCNU and added Gemzar. He must have seen something over the years.
Yes, that’s correct that the second transplant regimen is similar to TT2 for patients achieving less than a PR.
The BCNU is added because it takes the pressure off of the Melphalan as the sole drug responsible for eradicating the MM cells, and the Gemzar is added to the regimen because it prevents the MM cell DNA repair that is responsible for Melphalan resistance. It’s an extra insurance policy, if you will, to augment transplant 2 efficacy and eliminate the possibility of drug resistance. This is especially important in those patients that have very aggressive disease that could become resistant from transplant 1 to 2. And, yes, you are also correct and linking it back to what he was able to discern about transplantation and treatment in general from the trials done at the University of Maryland.
One last note and I'll leave you alone. It appears the University of Maryland did a phase II trial using BCNU, Mel, and Gemzar back in 1999. I wonder if that's where Dr. Tricot gained some of his insight into this combination. I wonder how the trial turned out and whether it ever went to phase III?
This was his trial and worked well. Unfortunately, the end result was hampered by the fact that they did only one transplant. The study was designed to see if one transplant with one year of intensive consolidation was as good as two transplants without consolidation. That was not the case.
Lastly, a question about maintenance:
First, since we're receiving velcade for 12 months during the maintenance cycle, isn't it likely that our MM will become resistant to the velcade? Upon relapse, what current options do we have now that the velcade is gone?
1). Resistance in cancer cells generally occurs when a high tumor burden is being exposed to relatively weak drugs. That’s one of the reasons, with the exception of short stints with transplantation, that we wait until post-consolidation to expose patients to velcade, thalidomide, and dex for a year (or two in the case of dex). Post-consolidation, the vast majority of patients have achieved either a complete or near-complete remission, and a few achieve only a very good partial remission. In all of those cases, there are few worries about creating resistant MM. If, however, a patient achieves a partial remission or less, he/she may need something else, and something stronger, than a Vel-dex-thal combo treatment, because then you’re dealing with tenacious, aggressive disease, and if high-dose chemo didn’t work, VDT is unlikely to yield any benefit. Also, in the unlikely event that a patient becomes resistant to VDT, velcade can often be coupled with other drugs (cytoxan, for instance, or oral ATRA), or you may get a non-velcade cocktail that consists of other combinations. I’m always astounded at how many different chemo combinations Dr. Tricot comes up with – and each with a unique rationale within an individual patient’s disease context. Typically, though, if you happen to progress after a tandem transplant, we would do another transplant, which tends to generate the most benefit in terms of resetting the myeloma clock back to remission. That’s one of the reason that we aim to collect at least 20 million CD34+ stem cells, because that’s more than enough for additional transplants. As scary as that prospect may sound to you right now, we have had patients that have undergone 4 transplants.
Last edited on Sat Apr 18th, 2009 01:22 am by DougC
|
