Combination Therapy for Immune Thrombocytopenia Treatment
A panel of experts who manage immune thrombocytopenia debate the potential for treating the condition with combination regimens in the future.
Bhavesh Shah, RPh, BCOP: Because we were talking about ITP [immune thrombocytopenia] having these 2 different mechanisms and the possibility of using a combination approach, I want to get your perspectives on that. There’s some combination in ITP that we know in refractory cases that we see in the pediatric patient population. Of course, a lot of times, we see it happening inadvertently, where a patient had received rituximab and didn’t have a response, but that response could be delayed. By the time you start a new agent, the patient may be having a response from the rituximab, so in that way you’re using a combination approach. Are you both using fostamatinib with any combinations? What is your experience with that?
David Hughes, PharmD, BCOP: This is a great question, but I want to highlight Ali’s point, and that’s the importance of real-world, evidence-based practice in ITP and its publication. It’s really important to recognize the combination approach, because a lot of these trials are done after extensive washout periods where patients have not seen therapy for weeks, and then they are treated in a naïve setting of a drug, and investigators watch what happens to the platelets.
Bottom line is that it doesn’t always happen that way in practice, as both of you are aware. We may have a patient on a TPO [thrombopoietin] agonist whose platelets are 1 million per mm3 1 day and then 2000 per mm3 the next week, then back up to 900,000 per mm3 and back down to 10,000 per mm3. It’s a common theme we see with a lot of the TPO agonists. An attractive option is, why not give them something like a SYK inhibitor and then combine that with an agent and a smaller dose of a TPO agonist. We don’t have large randomized trials to support that, but it is probably being done more in practice, especially in the relapsed setting.
Patient satisfaction and quality-of-life measures should also be considered. Some of these drugs require weekly injection, so patients will have to come to the clinic every single week. This condition is not 1 to undergo a “cure” or achieve remission forever. A lot of these patients are on these therapies indefinitely and to have them come into the clinic continually creates a problem for patients.
Because of the frequent clinic visits, a lot of these patients want to transition to an agent like fostamatinib. When fostamatinib initially came out, we had a patient who was a college student who could not keep coming in the clinic and missing her class for her injection because of the weekly administration. She asked to be switched to fostamatinib. In this setting, there’s no guidance on how to do this practice. If you just stop an injectable TPO, you might see the platelets fall to a dangerous level, especially in someone with a history of a previous bleed. It needs to be done in a slower way.
Many times, even though we may not necessarily use combination in the long term and keep these patients on therapy, it’s important to recognize what the safety is of using 2 agents in a short period of time to ultimately bridge from 1 therapy to another. As Ali said, it is important to consider what the disease biology actually does when you expose the patient to TPO—whether you expose the patient to a SYK inhibitor first. How does that alter the disease and affect subsequent lines of treatment? There are a lot of interesting questions jumbled in here. Ultimately, combination, sequencing, and this transition of “bridging,” is something that we should be thinking about in practice.
Ali McBride, PharmD, MS, BCOP, FASHP, FAzPA: David brought up a great discussion looking at these combinations and also, the discussion on the registry trial. If a patient fails therapy, we don’t give a washout of 4 to 6 weeks, we switch them immediately because the effect on the patient is detrimental. That is a very nice point you brought up, David, how that doesn’t actually fit into our clinical trial personnel. In most cases, we can’t put a patient on a clinical trial with an ECOG [performance status] 1, and some of these patients may not fall into that. For the sequencing and treatment, evaluation is appropriate.
Also, the other thing to tack onto that, which is something I deal with all the time, is reimbursement. If we’re doing combinations, steroids and rituximab are fine because we usually use them as premedications in most cases. When we get to these higher-cost therapies, we’re also facing some difficulties with combining because it falls into an off-label setting. Some of the issues we deal with in terms of reimbursement is we may actually be dealing with pathway discussions and therefore may follow that pathway. If we don’t have access to those therapies for earlier lines based on that ASH [American Society of Hematology Annual Meeting] trial, it may be tougher to actually get that patient on a SYK inhibitor or TPO a little earlier because of sequencing that some of the payers may have already implemented too.
David Hughes, PharmD, BCOP: Right.
Bhavesh Shah, RPh, BCOP: You guys echoed basically what we do in clinical trials, not what we do in the real world. Looking at all the things you both talked about, even looking at the response criteria used in the clinical trials, we have patients who are stable and have no bleeding events. Their platelets are nowhere near 50,000 per mm3, and even achieving a response criteria of 50,000 per mm3 using that is more of a clinical trial end point. As practitioners, we’re looking to minimize bleeding events in patients. That’s the true outcome, not a number of platelets that a patient achieves. It just shows how the clinical trial is not the same as how we practice in the real world.