How is ITP Therapy Evolving?

The blood disorder immune thrombocytopenia (ITP) is quite rare, with roughly 5-10 cases per 100,000 people. This disorder causes the body’s immune system to mistakenly attack and destroy its own platelets. Cleveland Clinic Cancer Institute is raising awareness about this little-known condition and evolving treatments for it.

ConsultQD recently spoke with hematologist Keith McCrae, MD, to learn more about patient needs and newly published guidelines to direct care. An active clinician and researcher, Dr. McCrae cares for patients with nonmalignant blood diseases, serves on the American Society of Hematology (ASH) ITP Guidelines Committee and is Editor-in-Chief of Blood Vessels, Thrombosis and Hemostasis. ASH published new ITP guidelines earlier this month.

Q: What is ITP and how is it diagnosed?

A: We see many patients in the Hematology clinic with ITP. Classically, we see low platelet count due to development of autoantibodies that react with platelets and cause them to be cleared prematurely, primarily in the spleen. They’re usually IgG antibodies but there are other mechanisms by which platelet counts can be reduced in ITP as well.

ITP can be classified as primary ITP, which is when there’s no obvious precipitating cause, or secondary ITP, which occurs in conjunction with other disorders, such as autoimmune diseases like lupus or hepatitis C, certain infections, low-grade lymphoproliferative disorders like CLL, or some lymphomas.

ITP may be hard to diagnose. There's no single laboratory test that you can just order, so you make the diagnosis clinically by finding a low platelet count, usually with other blood counts preserved. However, there are other conditions that can cause low platelet counts such as myelodysplastic syndrome or bone marrow failure and these must be excluded to make a diagnosis of ITP.

Q: Where are you seeing the most cases of ITP?

A: The disease can happen at any age. The most common age group for new ITP cases is people over 60. Children can also contract ITP, often after viral infections.

For children, roughly 75% of cases resolve within 6-12 months. It is most commonly a chronic disease in adults, although it’s become apparent that 20-30% of those cases will improve or resolve over time as well. Some of this improvement may be hastened by more aggressive therapy early in the course of ITP.

Q: In terms of adults, how has the treatment landscape changed in recent years?

A: It’s changed dramatically in the last 20 years, particularly since around 2007 when thrombopoietin receptor agonists became available. These were a new mechanism of treatment, which signals the bone marrow to produce more platelets. Before that, treatment was primarily steroids and IVIG and sometimes chemotherapy. More recently, we’re seeing:

• BTK inhibitors, which use a dual mechanism to stop the immune system from destroying platelets
• SYK inhibitors, which block an enzyme in phagocytic cells that are responsible for uptake of antibody-coated platelets

In terms of further advances, there are also additional novel approaches such as targeting the BAFF/APRIL pathway that drives B-cell survival and autoantibody production. There’s also a lot of interest in plasma cell-directed therapies such as daratumumab, which is approved to treat multiple myeloma. Bortezomib has also been used in ITP, and newer investigational plasma cell-directed agents are under study Some rheumatologic drugs like belimumab may have effects against ITP as well. Researchers are also studying the use of T-cell engagers and CAR T-cell therapy to treat ITP.

Q: How do you decide which treatment to use initially?

A: Historically, first-line therapy has been steroids, which are inexpensive but for most people they don’t achieve durable remission with these medications. Toxicities from steroids are significant, and include glucose intolerance, psychiatric manifestations, insomnia, bone loss and infection. Physicians must monitor for these side effects, as there is no easy way to prevent them. Note: In ITP, we recommend trying to limit steroid courses to six weeks or less.

Based on the new ASH guidelines, the suggested first-line therapy is rituximab plus steroids or a thrombopoietic agent plus steroids. The reason for this recommendation was to increase the potential for long-term responses in ITP after initial treatment. If successful, this reduces the chronicity of the disease and gives the patient a better opportunity to achieve a treatment-free remission.

Q: I understand that patient representatives were involved in the ASH guideline development. Can you talk a bit about their role?

A: The patient representatives are often asked to comment on preference of drug delivery modalities (e.g., oral or IV), tolerability and convenience. These thoughts are significantly weighed in the decisions of the committee.

Q: What treatments are recommended if initial therapy is no longer effective?

A: Recommendations for those who fail initial therapy have changed because drugs such as rituximab that formerly were used after initial therapy have now been moved to the initial therapy category. SYK inhibitors, BTK inhibitors and mycophenolate mofetil have moved in to take their place. Of course, when possible, we try to enter patients into new clinical trials if they are eligible and interested.

To make the treatment decision, we present patients with options based on the expected disease course and medication efficacy, and balance these needs along with the patient’s preferences. Some medications require intravenous infusions or subcutaneous injections while others are oral and so are easier for patients.

Medication choice depends on the individual situation. We’ve seen some cases of post-transplant ITP, or ITP in pregnancy that require special considerations and different pathways. Our team has managed a wide range of ITP cases and has a depth of experience with these medications as well as clinical trials in ITP and can manage difficult cases or consult with physicians looking for guidance.