Adding Quality of Life to Treatment Goals in Immune Thrombocytopenia

Immune thrombocytopenia (ITP) has long been managed to a platelet number, but a growing body of patient-reported outcome (PRO) data is complicating that shorthand, particularly for younger patients whose symptom burden and their platelet count do not move together.

In a virtual Case-Based Roundtable event for oncologists on the West Coast, Amit R. Mehta, MD, a hematologist-oncologist in private practice in the Durham, North Carolina, area and adjunct faculty at Duke University, reviewed PRO data and emerging second-line and beyond ITP therapies, and moderated discussion of a case built around a patient whose fatigue and heavy menstrual bleeding persisted well after her platelet count had recovered.

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This article is part 2 of a 2-part series from a Case-Based Roundtable event.

CASE SUMMARY

• A 38-year-old woman was diagnosed with primary ITP after presenting with petechiae, mucocutaneous bleeding, and a platelet count of 8 × 10⁹/L.
• She is a high school principal and otherwise healthy; prior to her diagnosis she ran 3 mornings a week.
• Following 4 cycles of dexamethasone, she presented with a platelet count of 17 × 10⁹/L (peak platelet count: 76 × 10⁹/L after cycle 2), heavy menstrual bleeding (hemoglobin: 9.6 g/dL), and increased anxiety and fatigue.
• Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) score: 23. She stopped running entirely and is using sick days to recover after heavy menstrual days.

EVENT RECAP

Mehta introduced the discussion with a 2021 multinational survey of more than 1500 patients with ITP and roughly 500 treating hematologists, which found that fatigue affected 85% of patients at some point in their disease course, yet physicians underestimated fatigue frequency by roughly 50% relative to what patients reported.¹ Additionally, Mehta told the participants that the survey showed that, “the fatigue level perceived by the patient does not correlate with the platelet count,”, a finding that reframes what “controlled” ITP should mean for someone like this case patient.

Polling the participants on initial treatment for this patient, the vote split evenly 3 ways among eltrombopag (Promacta), rituximab (Rituxan), and rilzabrutinib (Wayrilz), each drawing 33.3%.

Mehta said all 3 were defensible: the thrombopoietin receptor agonist (TPO-RA) eltrombopag directly targets her low platelet count, rituximab offers a finite dosing course that could spare a young patient years of daily medication, and rilzabrutinib’s mechanism as an oral, reversible Bruton tyrosine kinase (BTK) inhibitor, pairs platelet-directed activity with the fatigue benefit seen in its pivotal trial.²

CASE UPDATE

• The patient started on eltrombopag 50 mg daily; platelet count improved to 62 × 10⁹/L, but heavy menstrual bleeding and fatigue continued, with her FACIT-Fatigue score improving only from 23 to 27; she has not returned to running.
• She says she cannot make it through a full workweek and asks about discontinuation.
• Continued on eltrombopag 50 mg; platelet count subsequently fluctuates between 18 and 38 × 10⁹/L
• Returns to clinic: platelet count 19 × 10⁹/L, heavy menstrual bleeding ongoing with hemoglobin 9.1 g/dL, FACIT-Fatigue score of 21. Eltrombopag is discontinued. She declines splenectomy.

EVENT RECAP

Once eltrombopag was started and her platelet count rose to 62 × 10⁹/L without resolving her symptoms, the polling results shifted decisively: 42.9% would switch to rilzabrutinib, more than double the next closest option, rituximab, at 14.3%. Meng Zhao, MD, of Providence-Swedish Cancer Institute, asked if Mehta would treat based on fatigue alone if the platelet count were safely above 30 × 10⁹/L. Mehta said his answer has evolved. Traditionally, he would not; now, if fatigue is significantly affecting a patient’s life, he says escalation can be done as a defined trial, typically 2 to 4 months, to see whether raising the platelet count further also relieves the symptom, continuing only if it does.

Heavy menstrual bleeding added its own layer to this case. Mehta noted that in premenopausal women with chronic ITP, a platelet count that looks adequate on paper, 40 to 50 × 10⁹/L, may still be inadequate for someone experiencing significant menorrhagia, and that iron deficiency from chronic blood loss should always be ruled out before attributing fatigue to ITP itself. Ashok Bapat, MD, of Sutter Santa Rosa, cautioned that any premenopausal patient with new or worsening heavy bleeding also needs a workup to rule out endometrial cancer or fibroids rather attributing it to ITP. Mehta added a prescribing caution that patients on TPO-RA who are also considering estrogen-containing oral contraceptives for bleeding control should be counseled carefully, since combining the 2 compounds a thrombotic risk that TPO-RA therapy already carries on its own.

CASE UPDATE

• The patient was continued on eltrombopag 50 mg given stable platelet count at the time, but most recently, her platelet count has been fluctuating: from 18 to 38 × 10⁹/L.
• She returned to clinic: platelet count of 19 × 10⁹/L, heavy menstrual bleeding ongoing with hemoglobin of 9.1 g/dL, FACIT-Fatigue score of 21. Eltrombopag is discontinued. She declined splenectomy. ​

EVENT RECAP

By the final case update, eltrombopag’s inconsistent response and the patient’s declining FACIT-Fatigue score, prompted discontinuation. Polling on next steps, rilzabrutinib was the clear preference at 53.8%, followed by rituximab at 23.1%; a clinical trial referral and fostamatinib (Tavalisse) each drew smaller shares.

Mehta presented clinical trial data from the phase 3 ADVANCE IV trial (NCT04188379) of efgartigimod (Vyvgart), a neonatal Fc receptor antagonist that reduces circulating IgG autoantibodies. It sustained platelet response in 22% of patients vs 5% with placebo in the chronic population (P = .032), alongside meaningful patient-reported quality-of-life gains in its open-label extension.³ The phase 3 VAYHIT2 trial (NCT05653219) of ianalumab (VAY736), a B-cell activating factor receptor antibody, added to eltrombopag after first-line corticosteroid failure, more than doubled 6-month stable response rates over placebo plus eltrombopag (62% vs 39% with the 9-mg/kg dose; P = .045) while improving fatigue scores on both the PROMIS-Fatigue and ITP-PAQ-Fatigue instruments.⁴ Neither agent is yet FDA approved for ITP.

Several participants reflected on how much the session had shifted their perspective on quality-of-life management. “I wasn’t focused much on the fatigue aspect of ITP before, because platelet count is the primary goal,” said Pritam Tayshete, MD, of Virginia Mason Franciscan Health. “But now, with the study that you described, that’s something I’ll be looking at in more detail going forward.” Christopher DiSimone, MD, of Eisenhower Health, pointed out that patients like this one, insured through a school district plan, may receive coverage built around outdated guidelines, making it difficult to treat patients beyond platelet control even if their situation warrants it.

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DISCLOSURES: There were no known relevant disclosures.

REFERENCES

1. Cooper N, Kruse A, Kruse C, et al. Immune thrombocytopenia (ITP) World Impact Survey (I-WISh): Impact of ITP on health-related quality of life. Am J Hematol. 2021;96(2):199-207. doi:10.1002/ajh.26036

2. Kuter DJ, Ghanima W, Cooper N, et al. Safety and efficacy of rilzabrutinib vs placebo in adults with immune thrombocytopenia: the phase 3 LUNA3 study. Blood. 2025;145(24):2914-2926. doi:10.1182/blood.2024027336

3. Broome CM, McDonald V, Miyakawa Y, et al. Efficacy and safety of the neonatal Fc receptor inhibitor efgartigimod in adults with primary immune thrombocytopenia (ADVANCE IV): a multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2023;402(10413):1648-1659. doi:10.1016/S0140-6736(23)01460-5

4. Cuker A, Stauch T, Cooper N, et al. Ianalumab plus eltrombopag in immune thrombocytopenia. N Engl J Med. 2026;394(15):1503-1513. doi:10.1056/NEJMoa2515168