Clinical Trials Shaping the Use of Stem Cell Transplant for Myeloma

Published on

Topics include: Treatments

Patients who participate in clinical trials not only have an opportunity to receive the latest treatments, but allow research to move forward for everyone. In this interview, from the American Society for Blood and Marrow Transplantation's 2014 BMT Tandem Meetings in Grapevine, Texas, Dr. Sergio Giralt, of Memorial Sloan Kettering Cancer Center, and Dr. Philip McCarthy, of Roswell Park Cancer Institute, review the recent work of the Blood and Marrow Transplant Clinical Trial Network and detail what they hope to achieve through the DETERMINATION trial. With the participation of myeloma patients around the country, this trial may help discover whether induction therapy—the medicine given at the beginning of treatment—with an immunomodulatory drug and a proteasome inhibitor together might prevent some patients from ever needing high-dose chemotherapy using melphalan (Aleran), in conjunction with an autologous stem cell transplant.itor together might prevent some patients from ever needing high-dose chemotherapy using melphalan (Aleran), in conjunction with an autologous stem cell transplant.

View more programs featuring and


Andrew Schorr:

Hello and welcome to Patient Power. I’m Andrew Schorr. There has been tremendous progress in multiple myeloma, and this progress comes out of clinical trials.

Joining us now are two leaders in the area of clinical trials in myeloma, and that’s Dr. Sergio Giralt, from Memorial Sloan Kettering Cancer Center in New York City, and, Dr. Phil McCarthy from Roswell Park Cancer Institute in Buffalo, New York.

Dr. Giralt, let me start with you. There has been, really, an acceleration of clinical trials in myeloma, and it seems like it’s producing great benefits.

Dr. Giralt:

I think both Phil and I want to thank, first, all the patients who’ve participated in either the last three generations of national trials, which have actually set the stage for a national myeloma trial enterprise and actually is informing the treatments of the patients of tomorrow.

And every time we meet a myeloma patient, we remind them, look, the treatment you’re getting today is because people participated in trials previously, and they’re developing the modern treatments of tomorrow.

Since 2001, we’ve had a, the Blood and Marrow Transplant Clinical Trials Network, which has been funded by the National Heart, Lung, and Blood Institute, the National Cancer Institute. And this is the cooperation of large transplant centers, together with their myeloma colleagues, to develop what they think are the most important trials for today to inform the treatment of the patients of tomorrow.

We started with a 102, which we looked at the role of tandem autologous transplant versus an autologous followed by reduced intensity allogeneic transplant. This trial showed that for patients with standard risk disease, there was no benefit from the allogeneic transplant as up-front therapy.

We followed that with an endorsement of Phil’s, you know, really, we would say standard practice changing trial of CLGB100104. And I think I’m going to ask Phil, what did you feel, what a difference it made that we worked together?

Dr. McCarthy:

Thanks, Sergio, for that great introduction, because CL2B100104, which was developed through the Cancer and Leukemia Group B, which is now called the Alliance, looked at maintenance therapy with lenalidomide (Revlimid) after single autologous transplant for multiple myeloma. And it was a placebo-controlled trial. What that means is that there was no standard for treatment or maintenance or any type of therapy after single autologous transplant. And by having patients participate in this trial, it allowed us to see that there was a pronounced benefit in terms of when the disease came back. In other words, there was improved progression-free survival in patients who received lenalidomide compared to placebo. And once these results were clear, the study was unblinded. So what that meant is that patients were then allowed to cross over to lenalidomide after the study results were known. And despite this crossover, we still have seen a survival benefit in the patients who receive lenalidomide.

So this was very exciting in that it allowed us to be able to, as Sergio says, change practice and now offer to our patients a potential life-extending treatment as we develop new therapies, which Sergio will talk about, with regards to how we will keep our patients in remission and extend their lives.

Dr. Giralt:

And you see, Andrew, one of the most interesting things is, is while CLGB100104 was ongoing, we developed the stamina trial, and immediately, without any gap between trials, we were able to offer all myeloma patients across the country, in randomized trial, looking at what the role of consolidation therapy was.

At that time, the big question is, is there a role for a second autologous transplant? What is the role of consolidation with the new drugs, Revlimid, Velcade, dexamethasone, versus, based on the results of CLGB100104, just continued on maintenance therapy? And that’s set the stage for where we are today.

Andrew Schorr:

Now comes another big clinical trial, this one to determine the right timing of transplant in multiple myeloma. Seems like an evolution of your detective work.

Dr. McCarthy:

Yes, and the thing that’s so interesting is that fact that as new drugs get developed, previous work had shown that transplant appeared to be beneficial when compared to chemotherapy alone. But this was in the era where before novel drugs were available, such as proteasome inhibitors or immunomodulatory drugs or IMiDs.

This new trial incorporates IMiDs and proteasome inhibitors up front as part of the induction regimen, and then patients have all their stem cells collected up front, and then go down one of two pathways. Either they have their transplant early, or they receive more therapy with the idea that if and when their disease were to come back, they would then have a transplant at progression or recurrence of their disease.

All patients in both arms receive lenalidomide maintenance until progression of disease, and this is in distinction to the French portion of this study, where patients only receive lenalidomide for a year. And we think that may, may not be as beneficial.

But we’re going to be able to test this, not quite in a head-to-head comparison, but we’ll have two distinct cohorts where we have patients receiving lenalidomide until progression versus those who are going to receive it for a year.

The other thing is that there is a tremendous amount of correlative science studies that will be done on this trial so that there’ll be a better understanding of cytogenetic risk, molecular risk, and we may be able to identify patients who don’t need to have a transplant up front or may never need a transplant at all.

Dr. Giralt:

And we actually believe that there is a fraction of patients who, although having their stem cells collected in the freezer, will hopefully go on to have long-term disease control without ever having to be exposed to high-dose melphalan (Alkeran) and autologous transplant.

With the correlatives that Dr. Richardson and his team and Dr. Omunchi and the team have put together, we’re also hoping to be able to identify these patients up front so that we can guide therapy in a personalized way.

Andrew Schorr:

I want to thank both of you for being with us on Patient Power and for devoting your career, day in, day out, to helping people with multiple myeloma. Dr. Sergio Giralt, from Memorial Sloan Kettering Cancer Center in New York, and Dr. Phil McCarthy from the Roswell Park Cancer Institute in Buffalo, thank you and all the best.

This is what we do on Patient Power is connect you with leading experts. So be sure to be signed up for alerts on Patient Power, so you know anytime we post something new. I’m Andrew Schorr. Remember, knowledge can be the best medicine of all. 

Related Programs

The Importance of Myeloma Research: A Patient Advocate’s Perspective

Pat Killingsworth, who has been living with myeloma since 2007, shares his thoughts on the latest research news and what it could mean for patients.


Refining Modern Transplant Therapy: Current Studies in Myeloma

Myeloma patient advocate, Dr. Jim Omel, and Dr. Paul Richardson discuss a new trial examining the timing of stem cell transplant in frontline therapy.


Could Drugs Replace Transplant in Myeloma?

Dr. Thomas Martin helps us understand if various drugs can take the place of transplant in myeloma and what clinical research reveals.


Join Our Community Register for Events Read Our Latest Blog

Page last updated on April 28, 2014