Ralph V. Boccia, MD, FACP, LLC: There’s a Fc neonatal receptor monoclonal, a humanized monoclonal antibody that’s being presented right now as a single-arm study that looks promising. There’s a new oral BTK inhibitor.

Ivy Altomare, MD: A Bruton tyrosine kinase.

Ralph V. Boccia, MD, FACP, LLC: A Bruton tyrosine kinase inhibitor. It’s PRN1008. We happen to be on that clinical trial as well. We’ve accrued now, it’s another multinational trial, single-arm, open-label study. I think 7 patients have been put on it so far, but it’s interesting in a mouse model how effective it was. So what we know about BTK inhibition through ibrutinib and whatnot is that it’s not only critical for the B-cell receptor, but it’s also involved in Fc receptor pathway activation, much as SYK is.

Ivy Altomare, MD: Yeah. It functions similar to a SYK inhibitor then.

Ralph V. Boccia, MD, FACP, LLC: Exactly, and also B-cell activation. So it has the potential to block inhibition and block autoantibody production. And the nice thing about this particular drug is it does not inhibit collagen platelet aggregation, collagen-activated platelet aggregation. Now, having said that, there’s absolutely no evidence that bleeding correlates with platelet aggregation studies, although I think we all thought that the antiplatelet effect that ibrutinib caused, we know and could correlate, it turns out that is not the case. But it doesn’t inhibit that, and so perhaps the incidence of bleeding will be lower.

Ivy Altomare, MD: Hopefully.

Ralph V. Boccia, MD, FACP, LLC: Yes.

Ivy Altomare, MD: Yeah. So you have patients on this study now.

Ralph V. Boccia, MD, FACP, LLC: Yes.

Ivy Altomare, MD: Have you seen any bleeding?

Ralph V. Boccia, MD, FACP, LLC: No.

Ivy Altomare, MD: Yeah. Very interesting.

Ralph V. Boccia, MD, FACP, LLC: Yes.

Ivy Altomare, MD: And so is there anything at ASH [the American Society of Hematology Annual Meeting and Exposition] on PRN1008?

Ralph V. Boccia, MD, FACP, LLC: Just investigator meetings.

Ivy Altomare, MD: Anything that you know about that’s new that we should be aware of?

Amit Mehta, MD: The other thing to mention, as I think Dr Boccia alluded to earlier, was avatrombopag.

Ivy Altomare, MD: Yeah, and there’s lusutrombopag as well, which is approved for patients with thrombocytopenia and liver disease needing surgery.

Amit Mehta, MD: Needing surgery, yeah.

Ivy Altomare, MD: But not obviously for ITP [immune thrombocytopenia purpura].

Amit Mehta, MD: Yeah, purely in a preprocedural, preoperative setting. But avatrombopag may be something quite interesting if it gets FDA approved, which we may suspect. But we don’t have it officially yet as an FDA-approved medication. But I believe it can be taken with food or without food is 1 factor with it. The response rates that I saw just in the abstracts that have been presented is roughly— again in people who are heavily pretreated, just as we talked about, fostamatinib was studied in a heavily pretreated population, so was avatrombopag. Not surprisingly nowadays, people are enrolling on these studies after many years on various treatments.

But the response rate was over 30% for having some kind of sustained benefit. They had a specific definition for, I think, 6 out of 8 weeks toward the end of their treatment course, had to have a platelet count of 50,000 or more. So 50,000 is kind of like this general kind of standard that’s been applied, even though, as we said earlier, in real practice we may not be aiming for a number per se. But that’s the mark above which they’re aiming for response. And the adverse-effect profile may be a little bit different. It seems as if the liver risk may be less based on what we know so far. The headaches remain prominent with avatrombopag. What I saw in the abstracts that have been presented, arthralgias also are a feature of the medication in the clinical trials, interestingly enough.

Ralph V. Boccia, MD, FACP, LLC: I think it may give eltrombopag a run for the money.

Ivy Altomare, MD: Really?

Ralph V. Boccia, MD, FACP, LLC: Well, the fluid effect is major. I think that’s probably the biggest thing that we struggle with eltrombopag patients, you already talked about it. That and the LFTs liver function tests.

Amit Mehta, MD: Yeah.

Ivy Altomare, MD: Right, yup. I will mention that I have seen a data set on low-dose decitabine with some encouraging activity. I think the mechanism is that it actually induces megakaryocyte maturation. And then there’s also experience in Japanese literature of a new kind of recombinant thrombopoietin that doesn’t react with endogenous thrombopoietin and cause aplastic anemia. So we have a few things to look forward to.

I want to thank you both so much for participating in this. I really enjoyed our discussion. Before we conclude, I’d like to ask you both to give some closing remarks. Dr Boccia, why don’t you start?

Ralph V. Boccia, MD, FACP, LLC: Well, I think it’s an exciting time for patients who have ITP now that we have many more options. It appears though that we now, with some of these newer agents, can prolong their responses. And we may be able to reduce the potential adverse effects of the heinous corticosteroids that patients have been treated as the cornerstone and standard of care with.

Ivy Altomare, MD: Very well said. And Dr Mehta?

Amit Mehta, MD: Yeah, thank you, Ivy. My pleasure to come as well. My main take from the landscape of ITP now is that luckily we have so many new and robust treatment options available that have good response rates that we’re shying away from the older type of treatments that had very minimal responses. So the landscape has definitely changed where we have different mechanisms to utilize treatments that are FDA approved with robust responses and durable responses. Definitely an exciting time for the clinician treating ITP as well as the patients who are dealing with ITP. And hopefully we’ll build on this understanding about some of the ways to predict response and select the treatment for the mechanism active in this particular patient. Definitely quite exciting.

Ivy Altomare, MD: Yup, I agree. And I would like to conclude that I think that for ITP patients who are diagnosed, it can be very scary. This is a relatively rare disease, and I do want to mention that I have to remind myself to encourage patients to go to the PDSA [Platelet Disorder Support Association] support group and register and take advantage of those resources or other online support groups, because I think, in addition to all our hard work trying to manage their disease, that can be very, very helpful. And it’s something that physicians should take advantage of. Thank you both so much. This has been a lot of fun. On behalf of our panel, we thank you for joining us, and we hope you found this OncLive Peer Exchange® discussion to be insightful and informative.

Transcript Edited for Clarity