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Novel Therapies & Transplants in Multiple Myeloma

Insights From: Kenneth C. Anderson, MD, Dana-Farber Cancer Institute and Harvard Medical School; Rafael Fonseca, MD, Mayo Clinic; Noopur S. Raje, MD, Massachusetts General Hospital Cancer Center
Published: Monday, Mar 04, 2019



Transcript:

Rafael Fonseca, MD:
One of the most pressing questions is, what is the role of stem cell transplant? I declare myself a believer in the stem cell transplant. That’s an important therapeutic tool for patients with multiple myeloma. But as we get better and better with some of these combinations, the question will resurface—do we really need to add transplant? This is, of course, a big deal. Patients have to spend a couple of weeks in the hospital, if you do it as an inpatient, and we know of very significant toxicity.

It depends on how you approach the question, whether you’re a purist or you say, “Well, I’m going to extrapolate from the data I have.” I personally try to steer my patients towards stem cell transplant unless I have better information. And the reason for that is there are some studies that have looked at very long-term outcomes of myeloma therapy, where they show that patients who receive stem cell transplants and achieve a CR [complete response], at least there’s 1 notable study from Spain, can remain in that CR 20 years later. So I think transplant is a safe procedure. I realize it’s burdensome and has some significant toxicities, but I steer all my patients towards that.

Now in the study that was presented at ASH [the American Society of Hematology meeting] where they looked at KRd [carfilzomib/lenalidomide/dexamethasone], 1 of the arms of that study actually was KRd without transplant. And lo and behold, the rate of MRD negativity was similar with and without stem cell transplantation. The question of course is, will this be durable? They are not reporting on that yet. They just reported on the response rate.

So one of my standard lines is that, you know, we’ve spent the first 25 years studying in myeloma whether transplant helped, and we showed that it did. In the next 25 years, we’re going to study whether myeloma should be treated with transplant or not.

Kenneth C. Anderson, MD: Whether transplantation is relevant in the era of novel therapies is now being tested in several different clinical trials. I’ll mention the 1 that’s really the most important. A large collaborative effort between Dana-Farber Cancer Institute and the French investigators in IFM [Intergroupe Francophone du Myelome] have taken large numbers of patients. In particular, in our initial collaboration with France we treated 700 patients with newly diagnosed myeloma who received lenalidomide/bortezomib/dexamethasone. All had stem cells harvested, and half of the patients in a randomized fashion underwent high-dose melphalan and stem cell transplantation, and half of the patients didn’t. And in all cases lenalidomide maintenance was given for 1 year. That trial, which is primarily the French component of our collaboration, was published in the New England Journal of Medicine, and it showed that there’s about a 14-month progression-free survival benefit for doing the early transplant.

In the United States, we’re doing the same clinical trial—lenalidomide/bortezomib/dexamethasone, harvest stem cells, and randomize patients to an early transplant or not—but with the difference being that all of the patients in our trial received lenalidomide maintenance not just for 1 year but until progression. And that trial began in 2009. We don’t have data yet. And what that tells you is that now, 9 years later in 2018, both arms must be doing very well. If there was a significant difference in benefit, or a significant difference in adverse events, that big randomized phase III trial would have been interrupted.

So I think it’s fair to say that, as of now, the standard of practice is still a single transplant. In the future, if we have 4 drugs as initial treatment, or if we otherwise modify it, transplantation may no longer add value. But at least for right now the addition of novel agents before transplant, and after transplant as maintenance, has markedly improved transplant. So it does still remain a standard of practice.

Transcript edited for clarity/
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Transcript:

Rafael Fonseca, MD:
One of the most pressing questions is, what is the role of stem cell transplant? I declare myself a believer in the stem cell transplant. That’s an important therapeutic tool for patients with multiple myeloma. But as we get better and better with some of these combinations, the question will resurface—do we really need to add transplant? This is, of course, a big deal. Patients have to spend a couple of weeks in the hospital, if you do it as an inpatient, and we know of very significant toxicity.

It depends on how you approach the question, whether you’re a purist or you say, “Well, I’m going to extrapolate from the data I have.” I personally try to steer my patients towards stem cell transplant unless I have better information. And the reason for that is there are some studies that have looked at very long-term outcomes of myeloma therapy, where they show that patients who receive stem cell transplants and achieve a CR [complete response], at least there’s 1 notable study from Spain, can remain in that CR 20 years later. So I think transplant is a safe procedure. I realize it’s burdensome and has some significant toxicities, but I steer all my patients towards that.

Now in the study that was presented at ASH [the American Society of Hematology meeting] where they looked at KRd [carfilzomib/lenalidomide/dexamethasone], 1 of the arms of that study actually was KRd without transplant. And lo and behold, the rate of MRD negativity was similar with and without stem cell transplantation. The question of course is, will this be durable? They are not reporting on that yet. They just reported on the response rate.

So one of my standard lines is that, you know, we’ve spent the first 25 years studying in myeloma whether transplant helped, and we showed that it did. In the next 25 years, we’re going to study whether myeloma should be treated with transplant or not.

Kenneth C. Anderson, MD: Whether transplantation is relevant in the era of novel therapies is now being tested in several different clinical trials. I’ll mention the 1 that’s really the most important. A large collaborative effort between Dana-Farber Cancer Institute and the French investigators in IFM [Intergroupe Francophone du Myelome] have taken large numbers of patients. In particular, in our initial collaboration with France we treated 700 patients with newly diagnosed myeloma who received lenalidomide/bortezomib/dexamethasone. All had stem cells harvested, and half of the patients in a randomized fashion underwent high-dose melphalan and stem cell transplantation, and half of the patients didn’t. And in all cases lenalidomide maintenance was given for 1 year. That trial, which is primarily the French component of our collaboration, was published in the New England Journal of Medicine, and it showed that there’s about a 14-month progression-free survival benefit for doing the early transplant.

In the United States, we’re doing the same clinical trial—lenalidomide/bortezomib/dexamethasone, harvest stem cells, and randomize patients to an early transplant or not—but with the difference being that all of the patients in our trial received lenalidomide maintenance not just for 1 year but until progression. And that trial began in 2009. We don’t have data yet. And what that tells you is that now, 9 years later in 2018, both arms must be doing very well. If there was a significant difference in benefit, or a significant difference in adverse events, that big randomized phase III trial would have been interrupted.

So I think it’s fair to say that, as of now, the standard of practice is still a single transplant. In the future, if we have 4 drugs as initial treatment, or if we otherwise modify it, transplantation may no longer add value. But at least for right now the addition of novel agents before transplant, and after transplant as maintenance, has markedly improved transplant. So it does still remain a standard of practice.

Transcript edited for clarity/
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