ISH 2016
Relapsed Hodgkin lymphoma in PET positive patients
Dr Graham Collins - Oxford University Hospitals NHS Foundation Trust, Oxford, UK
In the Meet the Experts session we were particularly focussed on relapsed Hodgkin lymphoma and one of the major issues is what do we do with patients who have first line salvage chemotherapy and don’t become PET negative. If you do become PET negative it’s fairly straightforward, the cure rates with an autologous transplant, which is a fairly safe and reasonably well tolerated procedure, are very high. But if you autograft patients who are PET positive the cure rates are very low. Now, most of us in that situation would switch to a second line salvage treatment to try and get people PET negative and go to an autograft, and that’s fine if that happens, but often it’s quite difficult to get people PET negative. Do we then autograft them knowing that they’ve got a fairly low cure rate or do we abandon that strategy and allograft them, knowing that the cure rate is slightly higher with an allogeneic stem cell transplant but the risk of dying of the procedure is substantially higher and the risk of long-term complications like graft versus host disease is again higher. It’s a very difficult situation. In the UK we’ve generally gone down an allograft route, the rest of the world generally haven’t, they’ve tended to shy away from allografts in Hodgkin lymphoma.
Plus, now we’ve got novel agents coming in such as PD-1 inhibitors which aren’t routinely available but there are clinical trials. They seem to work very well at giving durable remissions, not usually complete remissions, but durable partial remissions. They may increase the risk of a subsequent allogeneic stem cell transplant by increasing the graft versus host disease risk because they’re immunostimulant drugs. So it’s really blowing the field wide open, the availability of these or the hopeful availability soon of these novel agents. So that’s really what the discussion was focussed on.
How does the UK and USA differ in regards to novel agents?
The US generally has earlier access to novel agents and with the new PD-1 inhibitors and the more durable remissions there’s an increasing sense in the US that patients who have PD-1 inhibitors shouldn’t go for an allogeneic transplant. That’s an interesting approach; in the UK and Europe, even with patients on trials for PD-1 inhibitors, we’re still keen to offer allogeneic transplants because the follow-up is longest, suggesting that that’s a curative approach. So we’ll see. PD-1 inhibitors might be curing people but we just don’t know, the follow-up is far too short. But there is definitely a US-Europe and in particular UK divide. The other thing that the US are very keen on, which we struggle with because of access to the drug, is if a patient relapses after an autologous transplant probably the standard treatment now is brentuximab vedotin. About 30% of people get into a complete remission and although it’s a minority they can do very well. Recent data suggests that about half of those patients never relapse, even if they don’t have a stem cell transplant. So what more and more people are doing now, particularly in the US, is not going for allogeneic stem cell transplant, stopping at eight cycles of brentuximab if they’re in a complete remission, and if they do relapse re-treating them, and they know there’s a fairly high chance of getting people in remission, and then going for an allogeneic transplant. Of course, if they don’t relapse they don’t need the transplant. The problem is re-treating people in the UK is much more difficult because it’s not routinely available so still in the UK, even if you get a CR, we’ll take most people to transplant. But it is certainly challenging our approach in that fairly rare population group.
What percentage of patients are difficult to treat?
Most patients with Hodgkin’s thankfully are cured with first line treatment, you’re looking at about an 80-85% cure rate for all comers. There are about 1,500 new patients in the UK each year so it is a relatively small group of patients who relapse. The issue is, though, they’re nearly always young and fit; there are a reasonable number of children who have Hodgkin lymphoma, so these are patients where it’s a real disaster if the disease does come back and managing them appropriately is absolutely key. So it’s a small patient group but it’s a very important condition to get right.
What is your take-home message?
I guess the take-home message is we aim for PET negativity prior to autograft, that’s a clear message. If you can’t get there really the take-home message is a careful discussion with the patient. There is no right answer, some patients feel very strongly they don’t want to be subject to an allogeneic transplant because of the short-term risks whereas others are thinking much more long term and are much more happy to go down that approach. So it is very important at that stage to involve the patient.
