Marginal zone lymphoma is a fairly rare subtype of non-Hodgkin’s lymphoma, it makes up around 10% of all non-Hodgkin’s lymphomas. It’s made up of three subtypes, that’s splenic, extranodal and nodal marginal zone lymphoma. In the frontline setting there are lots of treatment options and oftentimes responses are quite high. However, most patients, regardless of their frontline therapy, most patients will eventually relapse. At this AACR I’m presenting the results of a phase II trial with a specific inhibitor of PI3 kinase delta. This drug is called umbralisib, it’s an oral inhibitor of this specific isoform of PI3 kinase delta.
In this trial we enrolled patients with relapsed marginal zone lymphoma. All patients had to have at least one prior regimen including an anti-CD20 directed therapy. The trial enrolled 72 patients and we completed enrolment. I will be presenting the results of the first 42 patients who have at least nine months of follow-up.
What did you find?
In the phase IIb trial we enrolled 72 patients, 42 patients will be presented at this meeting. We found in those 42 patients with nine months follow-up a 52% overall response rate and this overall response rate was confirmed by an independent review committee. In the patients who received drug we saw the duration of response not yet reached and the progression free survival also not reached at 12 months. We predict that the progression free survival, based upon this first group of patients which have been analysed, to be around 66% at one year. We also saw adverse event profiles which were consistent with what we would expect from this class of drugs. This would include some transient transaminitis in the first couple of cycles as well as diarrhoea. Now diarrhoea is the thing that we probably watch closest with this class of drugs and with this agent it appears to be fairly mild and self-limited. So around 50% of patients experience some episode of diarrhoea, this usually lasted less than two weeks, around ten days, and was grade 1 or grade 2 in the vast majority of patients. In fact, only two patients had a grade 3 event.
What can we expect to see over the next few years?
Over the next couple of years we hope that this trial will lead to FDA approval of this drug for patients with relapsed marginal zone lymphoma. Now, ideally in the future to really improve patients’ long-term outcomes we need to see the combination trials with this drug and several other drugs like it. Ideally we’d also like to see this class of drugs move into the frontline setting, potentially in combination with chemotherapy or other targeted agents.