Treatment for immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA) is rapidly evolving. At the Best of Hematology & Breast Cancer 2026 conference, Dr. Thomas DeLoughery outlined how thrombopoietin receptor agonists, BTK inhibitors like rilzabrutinib, novel anti-CD38 antibodies, and complement inhibitors such as pegcetacoplan are reshaping care. With growing emphasis on early intervention, combination strategies, and treatment tapering, clinicians now have more options than ever to improve durable remission rates in these complex autoimmune hematologic disorders.

Dr. Thomas DeLoughery is a professor of medicine, pathology, and pediatrics in the Divisions of Hematology/Oncology and Laboratory Medicine at OHSU. His clinical interests include blood diseases, hemostasis, and thrombosis, subjects on which he has written extensively. He sees patients at OHSU Knight Cancer Institute. At the Best of Hematology & Breast Cancer 2026 conference in Seattle, Dr. DeLoughery presented a comprehensive overview of current and emerging treatment approaches for immune thrombocytopenia and autoimmune hemolytic anemia, with particular focus on novel agents and treatment strategies.

The transcript report below has not been reviewed by the speaker and may contain errors.

Overview of Immune Thrombocytopenia

The presentation began with a typical clinical scenario: a patient presenting with bruising and a platelet count of about 1,000, discovered incidentally with a PPI prescription. This represents probably the most common primary autoimmune disease encountered in practice—immune thrombocytopenia, estimated to occur in anywhere from 1 in 20,000 to 1 in 50,000 people. The condition involves autoimmune destruction of platelets, and classically patients present with very low platelet counts.

To this day, diagnosis really relies on clinical history, ruling out other causes of thrombocytopenia, and a normal blood smear. Initial therapy remains fairly standard: pulse dexamethasone at 40 milligrams per day for four days. One preferred approach is to repeat this every two weeks for a total of four cycles. Depending on the study referenced, this approach is sufficient to cure patients 30-50% of the time. For patients with very low counts, intravenous immunoglobulin at 1 gram per kilogram times one dose is used. Platelet transfusion is reserved only for truly life-threatening bleeding.

Second-Line Treatment Options For Immune Thrombocytopenia

For patients who do not respond to steroids, there have traditionally been three treatment choices. Splenectomy remains the only truly curative therapy and has been available for 100 years, but people are increasingly reluctant to pursue this option these days, so it's performed pretty infrequently. It's usually reserved for people who are really refractory or patients who simply want their therapy over and done with. Rituximab has been a longtime favorite, though it's important to remember it takes time to work. Thrombopoietic agonists are really rising in popularity.

Rituximab as Standard Second-Line Therapy

Rituximab has become the standard second-line therapy in many practices. The preferred dosing regimen is 1,000 milligrams times two doses, which is convenient for patients who come from far away and is easy to administer. However, it's important to remember that rituximab actually rarely cures people. James Bussel wrote years ago that while it provides good long responses, truly long remissions are pretty unusual. Many patients have received three or four courses of rituximab, requiring retreatment. It's also critical to remember that rituximab doesn't work fast—the average response time is six weeks, and clinicians need to give it three months before declaring treatment failure.

Thrombopoietic Agonists

The major development in ITP treatment has been the thrombopoietin receptor agonists, which are really effective in most patients. Romiplostim is administered subcutaneously once a week. Eltrombopag has been the standard oral therapy. Avatrombopag was highlighted with new data to be presented—it's a pill that's easy to use without significant dietary restrictions, and accumulating evidence suggests it's probably better than other options.

These agents do have the theoretical disadvantage of being forever therapy. However, interestingly, a sizable number of patients may actually go into remission with these agents. Multiple studies have shown that patients not responding to romiplostim or not responding to eltrombopag can be switched to avatrombopag with improved response rates. Response rates have been quite high at 60-80% in studies, and this has been matched in clinical experience. In fact, practice patterns are now shifting toward using avatrombopag first.

An interesting study called the Stop and Go study examined patients who had been on thrombopoietin receptor agonists for three months. Only about 48 patients were enrolled—these are ITP trials, not large cardiology trials with millions of participants—and treatment was stopped. Twenty-five patients, almost half and over half the group, remained with platelets over 30,000. This is fascinating, suggesting that perhaps treating for a while then stopping or cutting back may allow some patients to no longer need therapy.

Tapering Strategy for Long-Term Thrombopoietin Agonist Therapy

For patients on long-term thrombopoietin agonist therapy, tapering should be considered. If platelets are over 100,000, the dose can be reduced or changed to every-other-day dosing. This can be challenging logistically—some patients are literally on every-third-day dosing, which can be difficult for nursing staff to manage. Some people seem to need a lower dose to stay in remission, but many people can actually be weaned off completely. This is something being done more frequently in clinical practice.

Novel Agents for Refractory ITP

Despite rituximab and thrombopoietin receptor agonists, there are still patients with truly refractory disease who maintain platelets under 10,000. For these cases, there's a laundry list of treatment options that have been tried in ITP, with the approach being to start at the top and work down the list. However, newer and novel agents are emerging that may make this list considerably smaller.

Fostamatinib

Fostamatinib has been available for some time. It's a novel agent and a SYK inhibitor that blocks macrophage uptake of platelets. Seventy percent of patients achieve some response, and 28% achieve a sustained response that can actually be quite durable. The side effects can be challenging, with nausea and diarrhea seen in 20-30% of patients. There are also issues with hypertension. The clinical experience has been that many patients develop these side effects, making it somewhat challenging to use.

A fascinating small study from Britain examined combined therapy of avatrombopag and fostamatinib, showing very high response rates. What was particularly pleasing was that patients didn't have to wait three months for response—people who were going to respond did so within two weeks. This represents an area of interest for combining some of these newer therapies instead of using single agents. This has been kept as an option for really refractory patients.

Rilzabrutinib: BTK Inhibitor

A new agent highlighted was rilzabrutinib, a very specific BTK inhibitor that doesn't have the bleeding complications seen with other BTK inhibitors and doesn't show the cardiac complications either. There's very good data with strong trial results showing placebo-controlled evidence of response rates with this BTK inhibitor. What was particularly pleasing was the rapid response—patients can be told that when starting this drug, results will be known by the end of the month whether it works or not. The biggest side effect was just mild diarrhea in 23% of patients, but it's usually pretty well tolerated. Looking at the response curves, the response was pretty early and pretty durable. This agent is starting to gain significant uptake, is FDA approved, and is emerging faster than fostamatinib as a treatment option.

Novel Anti-CD38 Antibodies

Anti-CD38 antibodies, which target plasma cells and are known to be very effective for myeloma, are also becoming popular for ITP. A novel anti-CD38 antibody is being tested for ITP and is very well tolerated, requiring only a short course of therapy. The study of this novel antibody involved basically eight doses, with responses seen very early that appear to be very durable. A large phase 3 trial is currently ongoing.

BAFF Inhibition Strategy

BAFF is a B-cell growth factor, and belimumab is an anti-BAFF antibody. There was an early trial presented as a late-breaking abstract at ASH combining this with eltrombopag. This represents a very interesting idea of hitting ITP very hard early on, then dropping back. Patients received 16-24 weeks of eltrombopag with a brief course of the anti-BAFF antibody, achieving a 50% response rate that was durable, compared to 30% in the placebo group, which interestingly just received steroids and eltrombopag. While more study is needed, this is a very interesting approach of treating very aggressively early on, potentially wiping out the autoreactive B-cell clone and achieving a curable response.

Autoimmune Hemolytic Anemia

Autoimmune hemolytic anemia is less common and less well studied than ITP. The key point to remember is that very early use of rituximab is associated with higher numbers and more durable remissions, but the responses are still frustratingly incomplete. There are many studies and anecdotes of using daratumumab in autoimmune hemolytic anemia, though sadly there are no large randomized trials. It's very difficult to use off-label unless patients fortunately also have MGUS, which can help with approval. Studies have shown very rapid and very durable responses with daratumumab. Anecdotally, two patients with refractory pure red cell aplasia achieved remission with this agent. The expectation is that these drugs will see much more use for autoimmune diseases.

Pegcetacoplan for Complement-Mediated Hemolysis

Pegcetacoplan is a C3 inhibitor approved for paroxysmal nocturnal hemoglobinuria with very good data. Interestingly, it works not only in cold agglutinin disease, which would be obviously expected, but actually in warm antibody autoimmune hemolytic anemia as well. This suggests that much autoimmune disease, or at least hemolytic anemia, is mediated by the complement system. Responses have been seen in both warm and cold antibody disease, and this is expected to see more use going forward.

Current Practice Changes and Future Directions

Current practice changes include being more aggressive with patients who don't respond to steroids, using thrombopoietin agonists, especially avatrombopag. After patients achieve good response, attempts are made to taper the drug. Avatrombopag is being used more frequently, and the BTK inhibitor is being reached for earlier in patients who have failed thrombopoietin agonists.

For future directions, both daratumumab and novel anti-CD38 antibodies are very promising. They're very well tolerated and only need a short course of therapy. Early data looks exciting. Interestingly, drugs are now being borrowed from lupus and other autoimmune diseases. The idea of hitting ITP hard with a specific B-cell agent when first seeing patients is an intriguing concept that warrants further investigation.