As you know, autologous stem cell transplantation remains one of the most effective ways to treat myeloma. Any what we call transplant eligible patient who is fit enough, with not too much comorbidity, should get at some point an autologous stem cell transplantation. That remains true even though we have outstanding new drugs, new proteasome inhibitors, new IMiDs and combinations giving, indeed, excellent results. But still today, and that has been shown with numerous phase III trials comparing an upfront transplant versus a delayed one, every time the upfront transplant, autologous stem cell transplant, was superior and actually the very last trial was performed by the IFM in collaboration with the DFCI, the Americans, this is impress actually and the patients very briefly got VRD, Velcade Revlimid dex, and upfront transplant versus a delayed one at relapse and the option of upfront transplant was largely superior to the delayed one.
Now, even though we are improving myeloma treatment, relapse is also almost inevitable. So we within the EBMT, the European Society of Blood and Marrow Transplantation, decided to look at the registry and to see what was the role of autologous stem cell transplantation at relapse, specifically patients who already got two autologous stem cell transplantation. That actually is the case; in the past we used to do tandem autologous stem cell transplantation, meaning within three months’ time lag, and these people do relapse. We also have patients who have a first transplant, a first relapse, a second transplant and then a subsequent relapse and a third transplant. The question actually was what is the outcome of these patients and one of the questions was also is it detrimental, do you induce myelodysplasia and are there any benefits to doing such a third transplant? What we found is indeed there is a benefit but before talking about the benefit we didn’t find, in both scenarios, an increased myelodysplasia or secondary malignancies. So it’s feasible, of course you have a little bit higher haematotoxicity, haematological toxicity, but besides that it’s feasible and we didn’t find any increase of TRM, transplant related mortality, a little bit higher – it’s about 4% but no major issue in terms of safety.
The most striking result, and that’s the same in the first transplant, it depends on when the relapse occurs after the second transplant. Now I’m talking only on patients who got a tandem transplant and then had a first relapse. So if the first relapse is long enough and at least two or three years then you do really benefit from a third transplant with still a substantially long PFS and still a long overall survival. So we defined a kind of threshold that if you do relapse after tandem, and if I remember it’s at least two or three years after the tandem, then it’s worth doing a third transplant. In the other scenario it’s the same story, if I may say, but of course they relapse much earlier because they already got two relapses post two transplants so the relapse occurs much earlier. The threshold is at least 16 months. If it’s within 16 months it’s useless.
Are these being put into guidelines?
I would not say guidelines but I would say that if any clinician is considering at some point a third transplant this is interesting information and we’re reassuring, meaning that they will not experience too much toxicity and if the relapse occurs long enough after the second transplant there is some benefit.