How do you treat relapsed and/or refractory Hodgkin's Lymphoma?

For the vast majority of patients diagnosed with Hodgkin's Lymphoma, the cancer is cured by the first-line treatment. However, for some patients, the cancer returns after the treatment (relapses) and/or proves to be resistant to the treatment (refractory). Fortunately, there are second-line and third-line treatments that can still potentially cure such patients, albeit with increasing toxicity and risks. Unfortunately, a few percent of patients ultimately fail all three lines of treatment. It's at that point where the goal of the treatment changes to controlling the cancer, rather than curing it. As you will know, if you've been following my blog, that's where I currently find myself, hence my timeline page shows a fairly typical treatment path for those unfortunate few.

When it came to choosing a treatment to control my cancer, the medical team at my local hospital considered three options: Vinblastine, Gemcitabine and Brentuximab Vedotin. Opinions were divided about which treatment was best, but Vinblastine was chosen in the end. Part of the reason why opinions were divided is that Hodgkin's Lymphoma is a relatively rare cancer to start with, hence when you consider that only a few percent of those diagnosed with it find themselves requiring such treatment, there are very few patients from which experience/knowledge can be gained, and consequently the evidence to show which treatment is best is somewhat lacking.

Note: Radiotherapy was ruled-out due to the Hodgkin's Lymphoma being in an area that has previously been irradiated, i.e. it would likely just cause more harm than good. Donor Lymphocyte Infusions (DLIs), which are a kind of boost of the donor's immune system, was also ruled-out due to the extent of the skin GVHD that I'd already acquired from the Allogeneic Stem Cell Transplant; If the donor's immune system was going to cure me, it would have done already, so DLIs would have just been asking for trouble.

It's perhaps not surprising that had my care been managed by another hospital, a different treatment might have been chosen. For example: the hospital that I attended on a few occasions in Leeds would have also considered the PECC regimen, but would have probably chosen Brentuximab Vedotin; and the hospital that I regularly attended in Sheffield would have also considered Bendamustine, but it's unclear what would have been chosen, as my local hospital had already opted for Vinblastine, and there were no strong feelings that something else would have been a better choice.

If you have been keeping track, you'll realise that's already five different treatments that might control Hodgkin's Lymphoma (albeit not indefinitely) in circumstances similar to my own. None of those treatments are currently considered to be potential cures, but in the case of Brentuximab Vedotin, it's not entirely clear whether that might change in the future. The reason being that Brentuximab Vedotin is quite a new treatment, hence more time is required for it to show its full potential; Having said that, there are patients for which it has been used to achieve ongoing remissions that are now approaching lengths where the medical community typically start to consider a patient as cured.

Over the last couple of years, it has become clear to myself from numerous online sources that there are several other treatments available too. The most commonly used seem to be: Everolimus (Afinitor), Lenalidomide (Revlimid), and Vorinostat (SAHA). Occasionally, even Rituximab (Rituxan) is used, as it appears to indirectly benefit some patients, presumably by targeting some of the cells around the cancer (microenvironment) that are helping to support it; In my case, that treatment might also help with the skin GVHD. More recently, Nivolumab has attracted a lot of interest, and a few months ago was actually granted the breakthrough therapy status by the FDA for Hodgkin's Lymphoma; It seems that Nivolumab and Ipilimumab work well as a combination too. In other words, there are quite a number of treatments available.

The existence of treatments that may help to control (if not cure) Hodgkin's Lymphoma is clearly a good thing, but, in some ways, the number of them can be problematic too, as it adds to the difficulty in deciding which to choose, especially when you consider that some of those treatments may have a synergistic effect when they're combined. For example, there are currently clinical trials taking place where the combination of Bendamustine and Brentuximab Vedotin is being investigated, as that may prove to be better than either of the drugs alone. There are many other clinical trials taking place too, often in the US, but until all of the evidence is in, it's a bit of a guessing game.

Whilst a number of the treatments that I've mentioned are of the more novel/targeted variety, i.e. not the typically more blunt/harsh instrument that is chemotherapy, that's not to say that they're without any risks or side effects. Consequently, whilst patients can (and do) jump from treatment to treatment, using each for as long as they prove beneficial, all of the time hoping for new breakthroughs/developments, our bodies are only capable of taking so much, hence eventually there is bound to be that straw that breaks the camel's back. The hope is simply that the cure comes before the straw!