Historical data showing high cure rates for splenectomy in ITP is outdated. Recent data indicates that if a patient has already failed both a TPORA and rituximab, the chance of a successful splenectomy is less than 50%, repositioning it as a later-line salvage option.
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While platinum chemotherapy is considered the standard treatment after a patient progresses on a first-line ADC-IO combination, experts admit this is a standard "based on nothing." There is no clinical trial data to prove its efficacy in this specific setting; it serves only as a placeholder for new clinical trials.
Contrary to initial concerns, long-term safety data for thrombopoietin receptor agonists has allayed fears of malignant transformation and irreversible bone marrow fibrosis. The increased reticulin fibrosis observed is reversible upon drug discontinuation, offering significant reassurance for long-term prescribing.
The target platelet count for ITP patients should be tailored to their lifestyle, bleeding history, and quality of life goals. A normal platelet count is not necessary, and different thresholds are appropriate for different patients (e.g., someone planning a ski trip versus a sedentary individual).
ITP caused by immune checkpoint inhibitors (ICIs) is rare (0.25% incidence) but generally has a good prognosis. Most patients respond to standard first-line ITP therapies, and approximately 70% of those re-challenged with the ICI can continue treatment without a recurrence of ITP.
Beyond raising platelet counts, the newly approved BTK inhibitor rilzabrutinib provides dramatic improvements in the fatigue associated with ITP. This unique benefit, likely due to its anti-inflammatory properties, makes it a strong consideration for patients where fatigue is a primary quality of life issue.
The treatment paradigm for ITP is shifting towards early combination therapy. Recent clinical trials are investigating augmented first- and second-line regimens, such as combining dexamethasone with rituximab or romiplostim, to achieve more durable, treatment-free responses than monotherapy.
For myelofibrosis patients with profound splenomegaly but only moderate thrombocytopenia (platelets 50k-100k), fedratinib may be the best frontline option. It is arguably the most potent JAK inhibitor for spleen reduction and is approved for use in patients with platelet counts as low as 50,000.
Patients with ITP who fail or are intolerant to one TPO receptor agonist (e.g., eltrombopag) should not be considered a class failure. Switching to another TPO agent is a viable strategy that can induce a response in nearly half of these cases, particularly for intolerance.
Before initiating a CD20-targeting bispecific antibody in patients who have failed CAR-T therapy, a new biopsy is mandatory. Up to 30% of these patients experience CD20 antigen loss, which would render the bispecific therapy ineffective and necessitates choosing a drug with a different target.
In cases of severe ITP unresponsive to standard therapies, the anti-CD38 monoclonal antibody daratumumab can be highly effective. It works by eliminating the long-lived plasma cells responsible for secreting platelet autoantibodies, a mechanism distinct from other ITP treatments.