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.
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.
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.
Unlike older IMiDs where T-cell effects are secondary, CELMoDs have a powerful, independent pro-T-cell mechanism. This dual action is so significant that in the future, CELMoDs will be prescribed not just for their direct anti-myeloma effects, but specifically to enhance the efficacy of T-cell therapies like CAR-T and bispecific antibodies.
In newly diagnosed, transplant-ineligible myeloma, an iberdomide-based triplet (Iber-Dara-Dex) achieved 64% MRD negativity. This result is described as "astounding" because achieving MRD negativity is not even a realistic goal for comparable IMiD-based triplets like Dara-Len-Dex (the MAYA regimen). This sets a dramatically higher efficacy bar for frontline treatments.
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.
Named after the two-faced god Janus, yanalumab has a dual mechanism. It acts as a highly potent B-cell depleter while also blocking the BAF receptor pathway, which is critical for auto-reactive B-cell survival. This offers potential for deep, lasting, treatment-free remission.