ITP Armamentarium Expands With the Hope of Limiting Long-Term Steroid Exposure

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Kanwarpal S. Kahlon, MD, discusses the nuances of approaching treatment in ITP, updated guidelines to inform treatment selection, and recent data presented during the 2020 ASH Annual Meeting and Exposition that have the potential to advance the field.

Although patients with primary and secondary immune thrombocytopenia (ITP) can derive good responses from corticosteroids, long-term exposure to steroids is associated with unique adverse effects (AEs), said Kanwarpal S. Kahlon, MD, who added that the plethora of investigational agents in the ITP pipeline may lead to limited long-term steroid use down the road.

“Steroids are commonly used for patients with ITP, even well [after] early-stage or frontline treatment,” said Kahlon, in a virtual presentation during an OncLive® 2020 Institutional Perspectives in Cancer webinar on hematologic malignancies. “This is something we should be mindful of, particularly with cumulative steroid exposure over time and AEs.”

During the presentation, Kahlon, an assistant clinical professor in the Division of Hematology/Oncology at the University of California, Los Angeles School of Medicine, discussed the nuances of approaching treatment in ITP, updated guidelines to inform treatment selection, and recent data presented during the 2020 ASH Annual Meeting and Exposition that have the potential to advance the field. 

Guidelines Spotlight Multiple Treatment Avenues in Primary and Secondary ITP

“When we define ITP, it is as an isolated thrombocytopenia with a platelet count of less than 100,000/mcL that is not caused by or associated with another disorder,” said Kahlon. 

Primary ITP accounts for around 80% of all cases. The remainder of cases comprise secondary ITP, which arises from all other immune-mediated thrombocytopenia, including infection, immunodeficiency, autoimmune disorders, drug-induced factors, or lymphoproliferative disorders, such as chronic lymphocytic leukemia. 

In 2019, the American Society of Hematology (ASH) released updated guidelines that conditionally recommend patients with newly diagnosed ITP who have platelet counts of less than 30,000/mcL and are asymptomatic or have minor mucocutaneous bleeding to receive corticosteroids versus observation.1 

Steroids, such as prednisone, continue to be standard options for patients; however, short-course therapy (≤6 weeks) is preferred versus prolonged steroid exposure.

The International Consensus Report guidelines, which were also updated in 2019, echo the ASH guidelines with regard to frontline corticosteroids; however, anti-D immunoglobulin and intravenous immunoglobulin may also be utilized as initial treatment for patients with newly diagnosed ITP.2 

As systemic second-line therapy, the International Consensus Report guidelines recommend multiple options, such as eltrombopag (Promacta), avatrombopag (Doptelet), romiplostim (Nplate), fostamatinib (Tavalisse), and rituximab (Rituxan), which are all associated with robust clinical evidence. Other agents associated with less robust evidence include azathioprine (Azasan), cyclosporin A (Sandimmune), cyclophosphamide, danazol, dapsone (Aczone), mycophenolate mofetil, and vinca alkaloids.


Notably, the Syk inhibitor fostamatinib demonstrated stable platelet response compared with placebo in the FIT-1 and FIT-2 trials. Data from both trials served as the basis for the April 2018 FDA approval of the agent as second-line treatment for patients with ITP.3 

“[Patients derived] sustained responses on fostamatinib; however, once the drug was stopped, the platelets decreased, so similar to thrombopoietin [TPO]-receptor agonists, ongoing treatment is required,” explained Kahlon. “Fostamatinib [can cause] gastrointestinal [GI] and blood pressure AEs, which distinguishes it slightly from other second- and third-line treatments.”

Combination Therapy

Combination regimens with steroids have improved response rates versus steroids alone. During the 2020 ASH Annual Meeting and Exposition, findings from the randomized phase 3 FLIGHT study were presented, showing significantly fewer treatment failures in patients requiring first-line treatment for ITP with corticosteroids plus mycophenolate mofetil versus corticosteroids alone (HR, 0.41; 95% CI, 0.21-0.80; P = .0064).4 Similar outcomes were observed in patients with secondary ITP. 

The rates of AEs, bleeding events, rescue treatments, hospital admissions, and treatment-related AEs, such as infection, neutropenia, and GI events, were similar between arms. However, for unknown reasons, patients who received the combination experienced some decreases in quality-of-life parameters, including physical role, physical function, and fatigue. 


Additionally, the International Consensus Report guidelines highlight that subsequent splenectomy can be considered for eligible patients with ITP.2 Per ASH guidelines, the duration of ITP should be assessed for patients with ITP for more than 3 months who are dependent on or unresponsive to corticosteroids. Patients with ITP between 3 and 12 months should be recommended for primary treatment options with rituximab or TPO-receptor agonists. Patients with ITP longer than 12 months should be considered for primary treatment with rituximab, TPO-receptor agonists, or splenectomy.

ASH 2020 Sets the Stage for Future Directions in ITP

In addition to the FLIGHT study, multiple other studies regarding the management of patients with ITP were presented during the 2020 ASH Annual Meeting and Exposition, said Kahlon.

Findings from a single-center, retrospective study were presented.5 Of 71 evaluated patients with relapsed/refractory ITP, 11 had evidence of accessory spleen. In the 8 patients who underwent laparoscopic removal of accessory spleen, 100% responded and 87.5% obtained a complete response with the appearance of Howell-Jolly bodies on smear.  

Another study evaluated the role of complement inhibition.6 Patients with chronic ITP who were unresponsive to 2 or more prior therapies received treatment with the selective complement pathway inhibitor sutimlimab for a prespecified time with the potential for long-term retreatment with the agent following a washout period. Results of the phase 1 trial showed that sutimlimab induced rapid and durable responses with a manageable safety profile in a subset of patients with ITP who had inadequate responses to multiple prior therapies.

Another retrospective trial reviewed patients with ITP within a Medicare database to investigate the effects of cumulative steroid exposure.7 The findings showed that steroids were the most common type of therapy used in all lines of therapy up to the seventh-line setting.

Novel agents are currently in the pipeline to add to the armamentarium in ITP, including CD38-directed antibodies like TAK079, proteasome inhibitors like KZR-616, FcRn pathway inhibitors like rozanolixizumab, BTK inhibitors like ibrutinib (Imbruvica) or rilzabrutinib, sialylated immunoglobulin G agents, and stradomers. Additionally, recombinant TPO-receptor agonists may have utility in women who are pregnant.

How should we manage a 65-year-old male with ITP found to have platelets of 22,000/mcL on routine lab exam? His prior platelets were over 140,000/mcL. His hemoglobin is 12.5 and his white count is 7 with normal differential. He has occasional bruising and has experienced gum bleeding when brushing his teeth. He is primarily sedentary and has a body mass index of 27, meaning he is overweight. He takes hydrochlorothiazide, metformin, and atorvastatin.


  1. Neunert C, Terrell DR, Arnold DM, et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood. 2019;3(23):3829-3866. doi:10.1182/bloodadvances.2019000966
  2. Provan D, Arnold DM, Bussel JB, et al. Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv. 2019;3(22):3780-3817. doi:10.1182/bloodadvances.2019000812
  3. FDA approves fostamatinib tablets for ITP. FDA. April 18, 2018. Accessed February 3, 2021.
  4. Bradbury CA, Greenwood R, Pell J, et al. A multicentre randomised trial of first line treatment pathways for newly diagnosed immune thrombocytopenia: standard steroid treatment versus combined steroid and mycophenolate. the Flight trial. Blood. 2020;136(suppl 2):LBA-2. doi:10.1182/blood-2020-143563
  5. Blanco JMA, Salazar AS, Rangel-Patiño J, et al. Search for and extraction of accessory spleen in refractory immune cytopenias: effective or a waste in resources? Presented at: 2020 American Society of Hematology Annual Meeting and Exposition; December 5-8, 2020; Virtual. Abstract 18.
  6. Broome CM, Röth A, Kuter DJ, et al. Long-term safety and efficacy of sutimlimab in patients with chronic immune thrombocytopenia. Blood. 2020;136(suppl 1):14-15. doi:10.1182/blood-2020-139663
  7. Bussel JB, Tkacz J, Manjelievskaia J, et al. Long-term overuse of corticosteroids in patients with immune thrombocytopenia: a real-world analysis of a US claims database. Presented at: 2020 American Society of Hematology Annual Meeting and Exposition. December 5-8, 2020; Virtual. Abstract 849.