[Mark]

Re: Am in complete remission - do I need second transplant?

by Mark on Tue May 13, 2014 9:08 pm

Hi Cheryl G.,

I have written this before but I want to mention one more time that I was not going to do an auto ever. Not upfront, not relapse, ever. I am not biased or advocating their use, I am only trying to go by what studies show.

I think the reason the sentence

"With the use of novel agents and consolidation after transplantation, new studies will help to determine the role of tandem autologous HSCT."

is there is to cover what you are discussing. Why do you think he wrote that sentence if not to cover what you are discussing?

"If you look at a group of patients today who has achieved, for example, at least a VGPR in response to their initial therapy, you'll find the patients are not the same as those that achieved a VGPR 10 or 15 years ago. In the more recent group of patients, a much larger share of them are likely to have achieved a CR, or even sCR."

I am not exactly sure what you meant by that first sentence. Obviously better drugs used for induction lead to better responses in patients. I have never seen any doctor argue that novel agents are a bad thing so I am not sure what that point you are making. Novel agents and alkylators are not competing drugs. I think I am doing so well personally because my doctor used a novel agent, high dose alkylator, a polyclonal antibody (ATG), high dose fludarabine, and immunotherapy. They all played an important role in getting this high risk patient to a sustained MRD negative state that required no drugs to hold it for 3 years (though I would argue it was the immunotherapy that deserves the most credit).

Let me explain to you what I mean by principles not changing over time. BTW, I think the principle Dr, McCarthy was pointing out was that patients with a deeper response do better. The principle my therapy was based on comes from a study published in 2003 from patients treated in the 1990's. Here is what the study showed:

"Patients in complete clinical remission after myeloablative allogeneic stem cell transplantation (allo-SCT) were enrolled in a longitudinal study to assess the predictive value of molecular monitoring. Using polymerase chain reaction (PCR) for immunoglobulin gene rearrangements it was possible to generate a clone-specific molecular marker in 48 of 70 patients. Of these 48 patients, 16 (33%) attained durable PCR-negativity after transplantation, whereas 13 (27%) remained persistently PCR-positive and 19 (40%) showed a mixed pattern. The cumulative risk of relapse at 5 years was 0% for PCR-negative patients, 33% for PCR-mixed patients, and 100% for PCR-positive patients."

"Autologous stem cell transplantation is considered the standard treatment for patients younger than 65 years with multiple myeloma (multiple myeloma).1 While this approach produces complete or near complete remission in about 50% of patients, all patients will eventually relapse and the median duration of response is only 42 months.2 Conversely, allogeneic stem cell transplantation (allo-SCT) is associated with a significantly lower risk of relapse and can result in long-term disease-free survival.3-6 The reduced relapse risk after allo-SCT is probably due to the unique capacity of donor lymphocytes to recognize and kill recipient plasma cells. Several reports have supported the existence of this “graft-versus-myeloma (GVM) effect” in the allogeneic setting. However, the potential benefit of allo-SCT is offset by the high transplant-related mortality, and therefore there is currently widespread interest in the use of novel strategies using nonmyeloablative conditioning.7-13 "

"The attainment of persistent PCR-negativity has a favorable impact, but it is not synonymous of cure, since we observed a patient relapsing after 9 years of molecular remission (Figure 1B). The escape from the immunologic control of a residual myeloma clone can perhaps explain the occurrence of very late relapses.20 "
http://bloodjournal.hematologylibrary.org/content/102/5/1927.long

The principle that this study shows is that a donor immune system has a high probability of holding a molecular response long term. It does not say all patients should do an allo transplant or that allo should become the standard of care. The fact that novel agents have been approved since this study does not invalidate the principle that a donor immune system can hold a sustained molecular response long term. More recent studies have confirmed this observation using reduced intensity conditioning. Fifty years from now when they are on something like the 3rd generation of some new form of immunotherapy that has made allo transplants obsolete the principle that a donor immune system can cure blood cancer patients will still be true even though they will no longer be used.

Mark