Robert L. Talley, MD
Although the presentations of idiopathic thrombocytopenic purpura (ITP) and thrombotic thrombocytopenic purpura (TTP) differ, therapies for both blood disorders are greatly needed for patients who have exhausted the current available treatments, explained Robert L. Talley, MD.
ITP is often characterized as a diagnosis of exclusion with a bone marrow examination, explained Talley. Once diagnosed, it can be managed with frontline steroids, followed by fostamatinib (Tavalisse), thrombopoietin (TPO) receptor agonists, including romiplostim (Nplate) and eltrombopag (Promacta), immunosuppressive agents, and possibly splenectomy.
In April 2018, the FDA approved the SYK inhibitor fostamatinib as a second-line therapy for patients with chronic ITP who failed frontline therapy. Additionally, in December 2018, the FDA approved romiplostim for the treatment of pediatric patients aged ≥1 year with ITP for at least 6 months who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.
In November 2018, the FDA accepted a supplemental new drug application (sNDA) for avatrombopag (Doptelet), as a second-line treatment for patients with chronic ITP.1
The sNDA was based on positive data from the phase III Amendment 02 trial, in which avatrombopag demonstrated a prolonged platelet count ≥50 x 109
/L compared with placebo.2
TTP however, manifests in an abrupt presentation of neurologic deficits, anemia, or thrombocytopenia and requires immediate intervention with plasma exchange and immunosuppressive therapy, after which physicians can consider agents such as rituximab (Rituxan) or eculizumab (Soliris), said Talley.
In February 2019, the FDA approved caplacizumab (Cablivi) in combination with plasma exchange and immunosuppressive therapy for patients ≥18 years with acquired TTP. The approval of the nanobody was based on results from the phase III HERCULES trial, which revealed a statistically significant reduction in time to platelet count response and acquired TTP-related death or recurrence.3
In an interview during the 2019 OncLive®
State of the Science Summit™ on Hematologic Malignancies, Talley, a hematologist/medical oncologist at Centerpoint Medical Center, Sarah Cannon Cancer Institute, discussed current and potential future standards of care in IPT and TTP.
OncLive®: What have been the most notable advancements in ITP?
: Fostamatinib represents a brand new way to help people achieve a better platelet count so that they don't have bleeding or bruising; it supplements and compliments other modalities that patients may have exhausted.
What are the challenges with diagnosing TTP and ITP? How do these blood diseases present?
ITP is more or less a diagnosis of exclusion. If a patient has a low isolated platelet count and no other primary disease, then ITP becomes a diagnosis of exclusion. Serologic testing is something that has been discussed for a long time and was a subject of an ASH Clinical Practice Guidelines report in 2011. I wonder if it’s going to find more prominence over time. One doesn't need to do a bone marrow examination, but if there are other complicating medical diagnoses, then it's probably a good idea to do a bone marrow examination.
TTP is different altogether; it's sudden, explosive, and fatal as opposed to ITP, unless the platelet count is extremely low. In TTP, one has to make a diagnosis quickly. Even with the best therapies, there is still a [significant] mortality rate. Many of those patients are not old with many comorbidities; they are otherwise healthy.
What are other challenges that exist in these diseases?
There are some patients with ITP who are refractory to all of the therapies that we have. Steroids are great therapies; you can see a short-term response in about 70% of patients who are treated with high-dose steroids. Complications from steroids begin to be [accumulate] when patients need continuous steroids.
The older the patient and the higher the steroid dose, the more complications result. The other therapies carry finite complications with them, such as splenectomy; it’s fairly safe, but we would all love to avoid surgery. Additionally, the TPO receptor agonists are wonderful therapies. We have salvaged patients with them, but the expense is daunting for patients with limited means.
What have been the most impactful agents in these settings?
For ITP, high-dose steroids are acknowledged as [the predominant] first-line therapy with either prednisone or high-dose dexamethasone; that regimen salvages many patients. There is some advantage to adding an early immunosuppressive agent to rituximab.