What chemotherapy is used during an ASCT? Are there other options?

What is the chemotherapy used during a transplant? The major drug that we use in stem cell transplant is a drug called melphalan, which is a very old drug. It is related to a wartime chemical, you know, which is used to actually kill people called nitrogen mustard. And this agent basically attacks the DNA myeloma cells, or the plasma cells, and makes the DNA molecules that are two strands. They form cross-linkages between the strands, which basically destroys the function of the DNA and leads to cell death. And this drug turns out to be one of the most effective drugs in myeloma, even when we have all these new therapies. It still remains a very effective drug. You know, in myeloma, the concept is that everything that's effective has to be used at some point during the person's lifetime with myeloma. So if you miss out on a drug, you missed out on the benefit from that drug, which could sometimes be measured in years, for example. So melphalan is the drug of choice for transplants in myeloma. We find that 98 percent of transplants in America are done with this one drug as a single agent. In the old days, we also used to do whole body radiation along with melphalan, but it turned out that that was not necessary because melphalan alone was good enough, and whole body radiation had a whole host of side effects, which was not acceptable. For the most part, we have had high dose melphalan as the primary chemotherapy that we give before autologous stem cell transplant. In fact, the term transplant is kind of a misnomer. What we're really trying to do when we give the transplant in myeloma is give high doses of melphalan because melphalan is one of the most effective drugs we have against myeloma. But as a consequence of giving high dose melphalan, patients develop myelosuppression. So their blood counts can go really low and stay there because the stem cells get killed and damaged with high dose melphalan. So collecting stem cells and giving them back is a way of countering that effect of melphalan. What is the dose of melphalan given during transplant? We use a high dose of 200 milligram per meter squared for most patients. For older patients or patients with kidney dysfunction or comorbidities where we think they may not tolerate the 200 milligrams, we cut the dose to 140 milligrams. Doses higher than that have been studied, like to 280. People have also looked at adding other chemotherapy drugs to the melphalan or using other methods to condition the patient, like monoclonal antibodies targeted with radiation. But those are all experimental at this time. So the standard conditioning regimen is still melphalan at various doses. That's what's used at most centers. What are the alternatives to high dose melphalan? There have been other clinical trials that have combined proteasome inhibitors like bortizomib and carfilzomib, as well as old fashioned chemotherapy drugs like bucilfan with melphalan to show that there is an increased depth of response. And there is a suggestion that compared to historic data, that those kind of preparative regimen strategies may actually result in better progression-free survival for patients. In fact, MD Anderson did a randomized trial comparing melphalan with bu-melphalan in myeloma patients, both frontline newly diagnosed patients as well as patients who are in the relapse settings, increase progression-free survival benefit for myeloma patients. So those are some of the options. If a patient walks into the clinic today, what would be the standard of care regimen? It would still be melphalan. There are some other novel therapies in the pipeline that may be considered. There is the son of melphalan called melphlufen, which has been looked at in relapsed myeloma patients in low doses. I think the company is considering giving high doses of melphlufen with the caveat that perhaps it will be better tolerated than melphalan and may not have as many side effects. Thank you.