Medical Roundtable: Multiple Myeloma & Transplant Eligibility
Dr. Kalaycio: I think that's an important point. I do not think the Hematopoietic Cell Transplantation-Comorbidity Index4 is reliable in distinguishing patients who are good candidates for high-dose melphalan versus those who are not.
Dr. Lonial: I completely agree. It's interesting, because I actually completed a consent yesterday afternoon with a patient for transplant. He read our book on transplant on what to expect. As he was going through his concerns, it struck me that most of the toxicity we talk about with an autotransplant is really related to lymphoma transplant in which they’re getting three or four drugs as part of the conditioning. Most people get pretty sick with the lymphoma transplant, whereas most myeloma transplant patients report fewer problems. It’s an unusual patient who has a lot of toxicity associated with an autotransplant from myeloma, as opposed to a lymphoma patient.
Dr. Kalaycio: Agreed. We do not typically use cytogenetic analysis, or even molecular analysis, to determine whether a patient gets transplanted or not. Do you use those biologic stratification techniques?
Dr. Lonial: We do, and we use them on the front end to determine how we're going to maintain patients. Our approach now is not the risk adapted under-treatment of patients with good risk genetics, versus more aggressive treatment for patients with poor risk genetics in the induction setting as is recommended by other centers. We think everybody should get the absolute best induction therapy there is regardless of genetic risk. In our opinion, that’s an immunomodulatory drug (IMiD) proteasome inhibitor (PI) combination. We recommend that most patients proceed with transplant in the absence of a clinical trial.
We use that genetic information and diagnosis to base how we maintain them. For a standard-risk patient we would recommend lenalidomide maintenance. For a high-risk patient we would actually recommend lenalidomide, bortezomib and dexamethasone (RVD)-based maintenance. That is based on some data we published about 18 months ago where high risk patients, 17p deletion, t(14;16) are hypodiploid, actually have a much better progression-free survival, and overall survival by using triplet maintenance post-transplant.5 Then for the t(4;14), which is an intermediate group, we end up using just a PI as maintenance. We get the information and we use it to inform the maintenance approach.
Dr. Kalaycio: All right, now that article that you referenced is prospectively derived, but not a randomized trial, correct?
Dr. Lonial: That's absolutely correct.
Dr. Kalaycio: On a more practical note, talking about patients who you're thinking about transplanting—by whatever stratification algorithm you use—are you collecting stem cells on everybody regardless, or reserving them for future transplants? Or are you just collecting at the time you're actually doing the transplant?
Dr. Lonial: We collect on everybody after cycle 4. We collect enough for a couple of transplants so that we've got backup products available down the road, if we ever need them. The challenge with waiting until you’re ready to transplant is that if you get beyond cycle 4, it often gets more challenging to collect stem cells. Our approach is not dissimilar from the current Blood and Marrow Transplant Clinical Trials Network DETERMINATION trial, which is asking the question of early versus delayed transplant, but that everybody gets collected after four cycles of therapy.
Dr. Kalaycio: Lots of large centers adhere to that approach, but we have not. We have not found any trouble in our own experience, even with lenalidomide, when we collect stem cells at the time we need to do the procedure, assuming the lenalidomide has been stopped for a period of time.
With plerixafor, we found that we've been able to collect just about everybody regardless of prior exposure as long as there has been a time frame stopping lenalidomide before we actually try to collect. That goes for second remissions too. We don't seem to have any problem collecting in a second chemo-sensitive remission, or even a third. I guess we have not reached the point where we think it necessary to collect and cryopreserve. We wonder about that because there are costs involved. Insurance companies, we find, often are reluctant to pay for cryopreservation if you're not planning on using them right away.
Dr. Lonial: We've not run into that challenge as of yet. Truth be told, the cost of cryopreservation is a fixed cost. I know that there are centers that charge annually for cryopreservation—we don't do that. It’s a one-time fixed cost. I think that’s an interesting concept. For the collection of second and third autographs, your experience is not what I think is typically reported by many centers. These would be very interesting data to see, and to get out there in the literature, because that's a different model than I think many of us have approached. It would be good to get that information out.
