Phase II trial of nivolumab combined with ibrutinib for patients with Richter transformation

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Published: 17 Dec 2018
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Dr Nitin Jain - MD Anderson Cancer Centre, Houston, USA

Dr Nitin Jain speaks to ecancer at ASH 2018 about the trial looking at the combination of nivolumab and ibrutinib for patients with Richter transformation.

He reports that 42% of 24 patients had a response to the therapy and that 4 of the patients that had a response were then able to have an allotransplant.

Dr Jain explains that, although immune toxicity was a worry, very minimal toxicity was seen and the only side effects were from ibrutinib which they are accustomed to.

The Richter transformation is an aggressive transformation of CLL which occurs in approximately 5% of patients. Really there is no true standard of care, patients get chemo-immunotherapy as a treatment and then if you look at the results most of the patients unfortunately on average the median survival is less than one year. So this is a very tough disease.
A few years ago, based on some other data which was reported by the Mayo Clinic group that the single agent pembrolizumab, which is a PD-1 drug, may have clinical activity in patients with Richter’s transformation, we designed a study where we used nivolumab, a PD1 drug, in combination with ibrutinib for Richter’s transformation patients. So we reported at the ASH meeting 24 patients we have treated and 10 out of 24 patients had a response to therapy. So overall 42% of the patients responded and notably four of these patients were able to go to an allotransplant so that’s another feature that four of the ten who responded were able to go to an allotransplant.

In terms of the immune toxicities which we generally worry about whenever we use checkpoint inhibitors we saw very minimal immune toxicities in these patients and most of the side effects were related to ibrutinib which are within the line which you would expect with ibrutinib.

So overall this provides another approach, a potential approach, to treat patients with Richter’s transformation and it’s a chemotherapy free approach. So this especially may be appealing in situations where you have genomic aberrations such as deletion 17p, p53 where chemotherapy generally doesn’t work very well. So at least for those patients this could be a consideration.

The other things which have been done in the context of immunotherapies are the CAR T strategy. So there have been trials looking at CAR T-cell strategy which is obviously an approved strategy for ALL and non-Hodgkin’s lymphoma. But specifically treating patients with Richter’s transformation there was a report from the Fred Hutch group last year looking at that. Then also stem cell transplant, which is a kind of immune therapy, is also a well-established modality.