Comment: New PD-1 checkpoint inhibitors for treating Hodgkin lymphoma

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Published: 7 Dec 2014
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Dr Catherine Bollard - George Washington University, Washington, USA

Dr Bollard talks to ecancertv at ASH 2014 about key abstracts highlighted by the conference and their implications for the field.

She comments first on the use of checkpoint inhibitors to manipulate the PD-1 pathway, touching first on Professor Armand's work with nivolumab and then Professor Moskowitz's study on pembrolizumab, both of which addressed Hodgkin lymphoma. 

Read the news story here.

Dr Bollard is also a member of the Division of the Blood and Marrow Transplantation and senior scientist at the Children National Health System's Center for Cancer and Immunology Research at Children’s Research Institute. She is the Principal Investigator and the Sheikh Zayed Institute for Pediatric Surgical Innovation.

ASH 2014

Comment: New PD-1 checkpoint inhibitors for treating Hodgkin lymphoma

Dr Catherine Bollard - Texas Children's Hospital, Houston, USA

Now we’ve been hearing about checkpoint inhibition in solid tumours; we’ve heard a lot here at ASH. Nivolumab, the presentation of Dr Armand, what did we see and what are the implications here of looking at the PD1 pathway and using it therapeutically?

In Hodgkin’s lymphoma in particular, which is traditionally a tumour which we know is responsive to the immune system, here you can see that in a tumour which uses many, many strategies to overcome the immune attack that if you take away one of the strategies, which is in this case PD1 expression on the tumour cells, and Dr Armand very elegantly showed that these patients did have up-regulation of PD1 on the tumour cells, and when you relieve that blockade suddenly the immune system now is able to do its job and target and kill these cancer cells.

How impressed were you with the results in these refractory and relapsing patients?

The responses are incredible when you see over 80% responses in patients who had had many… a third of patients had had over six lines of therapy, so these are very heavily pre-treated patients. So this with a single agent therapeutic is an incredibly impressive response.

Does it deserve, as Dr Armand seemed to be suggesting, breakthrough status? I know the FDA is considering this.

Absolutely and I think that the next question will be what do you combine it with? Do you combine it with chemotherapy or do you combine it with other immunotherapeutic strategies such as targeting CD30, such as looking at other ways to overcome the immune evasion with CTLA4 blockades etc?

Still with Hodgkin’s disease, PD1 blockade with pembrolizumab, that’s another similar agent to the one that Dr Armand was talking about but Craig Moskowitz was giving us some fairly impressive, he called it compelling, data. What do you make of this? This was in Hodgkin’s lymphoma.

Yes, so actually both centres were involved with both PD1 blockers and honestly the responses are very comparable in both studies. One says 66% responses, the other was 80%, but with low numbers and these are, as I said, very heavily pre-treated patients so again it’s still extremely impressive and I really look forward to the advanced stage phase studies for these agents in Hodgkin’s lymphoma.

So it really looks as if this PD1 blockade is re-enabling the ineffective immune infiltrating cells then, does it?

Correct. Re-enabling them, yes.

What do you think doctors should take home from those two papers then?

What they should take home is that ultimately there are a lot of very exciting therapies out there for Hodgkin’s lymphoma now. We are seeing more and more how the immune system is incredibly important for controlling this disease and ultimately what we as physician scientists need to be working on is how can we transform the therapies for these patients to remove chemotherapy and to just focus on overcoming tumour immune evasion as a way to treat this disease.