Tuesday, November 17, 2015

ASH: Ibrutinib and Follicular Lymphoma

Here we go: Time to get into the abstracts for the ASH conference, where researchers will present the latest and greatest on all things related to blood diseases, including Follicular Lymphoma. It looks like CLL is going to get a lot of coverage again this year, just based on the number of presentation listed. Follicular lymphoma doesn't have nearly as many, but there is some interesting stuff in there, in my opinion.

There are several sessions that focus on Ibrutinib, the BTK (Bruton's Tyrosine Kinase) inhibitor. BTK is an enzyme that plays a role in B-cell development. By cutting off that enzyme, Ibrutinib stops B cells from developing. FL is, of course, a B cell lymphoma. 

I saw three interesting Ibrutinib/Follicular Lymphoma abstracts.

The first is "Ibrutinib Plus Rituximab in Treatment-Naive Patients with Follicular Lymphoma: Results from a Multicenter, Phase 2 Study." The title is pretty straightforward: in a phase 2 clinical trial, patients who had not received any treatment were given Ibrutinib and Rituxan (Rituxan once a week for four weeks, and Ibrutinib every day -- it's a pill, taken by mouth, for as long as it was tolerated or effective. The Overall Response rate was 82%: 55% had a Partial Response and 27% had a Complete Response. (The remaining 18% had stable disease.) Side effects seemed mostly tolerable, and in line with the side effects for Rituxan and other Ibrutinib combinations. Good news for this combination.

A second study,  "Long-Term Follow-up and Analysis of Dose Groups with Ibrutinib in Relapsed Follicular Lymphoma," tried to determine the best dose for straight Ibrutinib for patients who had relapsed or refractory Follicular Lymphoma (that is, their last treatment stopped working, or didn't work in the first place). This was a small study -- only 16 patients. 8 were given a low dose, and 8 were given a high dose, and patients kept taking it until it stopped working or side effects got too bad. The high dose group did better -- all 8 had a response, and it lasted 12 months (median). The lose dose group lasted 4 months (median), and only 2 had a response. Progression Free Survival was also considerably higher for the high dose group (24 months vs 9 months). The study suggests that higher doses might be better (measured by mg per kg of body weight) than the current standard of 560mg (whatever the patient's body weight) currently being used.

Finally,  "Phase I Study of Rituximab, Lenalidomide, and Ibrutinib in Previously Untreated Follicular Lymphoma (Alliance 051103)" looks at R-Squared (Rituxan + Revlimid/Lenalidomide) plus Ibrutinib. As the abstract points out, R-squared seems to be working on FL, so there are several attempts to make that combination even better by adding other agents -- in this case, Ibrutinib. Results were good -- 91% Overall Response, close to the 93% Response for R-squared. However, there was a "significant incidence of rash," which the researchers say is common with Ibrutinib. The Conclusion mentions the Response Rate and the high rash incidence, but doesn't say whether that justifies moving on to a phase 2 trial (it might also be too early in the study to decide that).

So there are your three interesting Ibrutinib and Follicular Lymphoma sessions at ASH. 

It's important to point out that Ibrutinib is not yet FDA-approved for Follicular Lymphoma (though it is for some other blood cancers), but there seem to be a whole bunch of trials going on that involve Ibrutinib, at varying levels of success. It seems likely that it will get FDA approval, in some form, at some point. But these abstracts show that it still seems like it might be a while before we see that approval, since it's pretty early still. It also seems more likely that we'll see success by combining Ibrutinib with something else, rather than seeing it being used on its own.

Still, some good stuff here.

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