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Transplant Timing in Multiple Myeloma

Panelists: Shaji Kumar, MD, Mayo Clinic; Heinz Ludwig, MD, Wilhelminen Cancer Research Institute; Maria Victoria Mateos, MD, PhD, University Hospital of Salamanca
Published Online: Thursday, May 18, 2017



Transcript:

Heinz Ludwig, MD:
I think transplant is still a very valuable treatment option and should be offered to every patient. In Europe, patients prefer transplant as frontline treatment, but there may be patients who achieve a very good remission, MRD-negative, after induction. I think they still should collect stem cells, and transplant may be an option as treatment at relapse. It’s a very good option. If there’s a long interval between first-line treatment and relapse, then transplant is fantastic. It’s a short treatment and it’s a highly effective treatment.

The question is, what is the optimal timing for transplant? Again, there are different philosophies and it depends very much on patient perception. From the new studies, which have recently been presented, we know that we improve the quality of response, we improve the rate of MRD-negativity with upfront transplant, and MRD-negativity correlates with better survival. But, at this point in time, we can just say that transplant improves progression-free survival. The data on overall survival do not show a difference between transplant and conventional therapy, meaning conventional therapy given at frontline and then transplant at relapse. So, we have to wait for more mature data when it comes to overall survival.

Our hope is that is what is known. Good-risk myeloma patients benefit most from good treatments, so transplant is an excellent treatment. The hope is that, after 4, 5, or 6 years, the curves will diverge and those who present with good-risk features will show a benefit in overall survival. But I must say, at this point in time, this is wishful thinking. The data are -- not there to say this is cut in stone, so we have to wait for that—but the benefit in getting a better quality of response is substantial in them, and also the treatment duration is short. It’s shorter than 12 cycles of an induction therapy because they just need 4 cycles, transplant, and then maintenance or you can put in consolidation after transplant maintenance, but it’s shorter than 12 cycles or 18 cycles of any other regimen.

Shaji Kumar, MD: There’s increasing debate about the role of stem cell transplant in myeloma, and this is a question that comes whenever a new drug or a new combination with a high degree of efficacy is adopted into practice. With transplant alone, before the new drugs came along, we had maybe about one-third of the patients getting a complete response to treatment. We can get that, or an even better complete response rate, with the triplet regimens that we use nowadays. So, rightly so, the question of transplant has again come up. What we know from some of the recent phase III trials is that transplant still plays a very important role in the management of multiple myeloma.

The best example is the French study, which looked at patients getting bortezomib/lenalidomide/dexamethasone as their initial therapy. Patients were randomized to get either an autologous stem cell transplant or continuing on the bortezomib/lenalidomide/dexamethasone. All patients then had some additional consideration with the same triplet regimen for 2 cycles, and they all went on lenalidomide maintenance. So, if you look at the control arm of that study, it is lenalidomide/bortezomib/dexamethasone initial therapy followed by lenalidomide maintenance, which is what people often would do if they didn’t go to a stem cell transplant. And in that study, it was clearly shown that when you get a stem cell transplant, you get a deeper response and you get longer progression-free survival. And we know from prior studies that early transplant also translates to a better quality of life.

Now in this particular French study, there was no difference in the overall survival, which is consistent with what we have seen in the past. So, it tells you that, yes, transplant early or delayed, can still have a positive impact on the outcome of these patients. But transplant should not be abandoned as a modality for patients with myeloma. I think transplant continues to be a critical part of the myeloma therapy in patients who are eligible to undergo a stem cell transplant, and our goal should be to get every eligible patient to have a stem cell transplant. At least in the initial stage, we should collect the stem cells with the intent to transplant them at some point during the course of their disease.

Now the second important aspect from the transplant is, increasingly, we have treatments which can have cumulative effects on the bone marrow. This is unusual that for somebody who has continuously been on therapy for 3 to 4 years, now their bone marrow reserve has really gone down and they’re unable to tolerate the new medications. So, doing a stem cell transplant at that time has a dual role of controlling the disease but also reconstituting their bone marrow, which allows them to get treatments they otherwise would not have.

The other side of the coin is, when do we do the transplant? The ideal time to do the transplant, based on these studies, again, is early. The early transplant clearly improves the progression-free survival compared to not doing a transplant as part of the initial therapy. However, for whatever reason, if that patient does not want an early transplant, collecting the stem cells and doing the transplant later on still gives a comparable overall survival. So, at least 1 of the 2 approaches should be considered.

Transcript Edited for Clarity
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Transcript:

Heinz Ludwig, MD:
I think transplant is still a very valuable treatment option and should be offered to every patient. In Europe, patients prefer transplant as frontline treatment, but there may be patients who achieve a very good remission, MRD-negative, after induction. I think they still should collect stem cells, and transplant may be an option as treatment at relapse. It’s a very good option. If there’s a long interval between first-line treatment and relapse, then transplant is fantastic. It’s a short treatment and it’s a highly effective treatment.

The question is, what is the optimal timing for transplant? Again, there are different philosophies and it depends very much on patient perception. From the new studies, which have recently been presented, we know that we improve the quality of response, we improve the rate of MRD-negativity with upfront transplant, and MRD-negativity correlates with better survival. But, at this point in time, we can just say that transplant improves progression-free survival. The data on overall survival do not show a difference between transplant and conventional therapy, meaning conventional therapy given at frontline and then transplant at relapse. So, we have to wait for more mature data when it comes to overall survival.

Our hope is that is what is known. Good-risk myeloma patients benefit most from good treatments, so transplant is an excellent treatment. The hope is that, after 4, 5, or 6 years, the curves will diverge and those who present with good-risk features will show a benefit in overall survival. But I must say, at this point in time, this is wishful thinking. The data are -- not there to say this is cut in stone, so we have to wait for that—but the benefit in getting a better quality of response is substantial in them, and also the treatment duration is short. It’s shorter than 12 cycles of an induction therapy because they just need 4 cycles, transplant, and then maintenance or you can put in consolidation after transplant maintenance, but it’s shorter than 12 cycles or 18 cycles of any other regimen.

Shaji Kumar, MD: There’s increasing debate about the role of stem cell transplant in myeloma, and this is a question that comes whenever a new drug or a new combination with a high degree of efficacy is adopted into practice. With transplant alone, before the new drugs came along, we had maybe about one-third of the patients getting a complete response to treatment. We can get that, or an even better complete response rate, with the triplet regimens that we use nowadays. So, rightly so, the question of transplant has again come up. What we know from some of the recent phase III trials is that transplant still plays a very important role in the management of multiple myeloma.

The best example is the French study, which looked at patients getting bortezomib/lenalidomide/dexamethasone as their initial therapy. Patients were randomized to get either an autologous stem cell transplant or continuing on the bortezomib/lenalidomide/dexamethasone. All patients then had some additional consideration with the same triplet regimen for 2 cycles, and they all went on lenalidomide maintenance. So, if you look at the control arm of that study, it is lenalidomide/bortezomib/dexamethasone initial therapy followed by lenalidomide maintenance, which is what people often would do if they didn’t go to a stem cell transplant. And in that study, it was clearly shown that when you get a stem cell transplant, you get a deeper response and you get longer progression-free survival. And we know from prior studies that early transplant also translates to a better quality of life.

Now in this particular French study, there was no difference in the overall survival, which is consistent with what we have seen in the past. So, it tells you that, yes, transplant early or delayed, can still have a positive impact on the outcome of these patients. But transplant should not be abandoned as a modality for patients with myeloma. I think transplant continues to be a critical part of the myeloma therapy in patients who are eligible to undergo a stem cell transplant, and our goal should be to get every eligible patient to have a stem cell transplant. At least in the initial stage, we should collect the stem cells with the intent to transplant them at some point during the course of their disease.

Now the second important aspect from the transplant is, increasingly, we have treatments which can have cumulative effects on the bone marrow. This is unusual that for somebody who has continuously been on therapy for 3 to 4 years, now their bone marrow reserve has really gone down and they’re unable to tolerate the new medications. So, doing a stem cell transplant at that time has a dual role of controlling the disease but also reconstituting their bone marrow, which allows them to get treatments they otherwise would not have.

The other side of the coin is, when do we do the transplant? The ideal time to do the transplant, based on these studies, again, is early. The early transplant clearly improves the progression-free survival compared to not doing a transplant as part of the initial therapy. However, for whatever reason, if that patient does not want an early transplant, collecting the stem cells and doing the transplant later on still gives a comparable overall survival. So, at least 1 of the 2 approaches should be considered.

Transcript Edited for Clarity
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