Eltrombopag Induces Complete Platelet Responses in Patients with Lymphoproliferative Disorders and Treatment-Resistant ITP

Results from a small phase II trial suggest that treatment with eltrombopag was associated with sustained platelet responses and complete responses (CRs) in patients with immune thrombocytopenia (ITP) secondary to chronic lymphoproliferative disorders who have not achieved adequate benefit from other therapies. The authors, led by Carlo Visco, MD, from San Bortolo Hospital in Vicenza, Italy, noted that achieving this level of platelet response could allow many patients to postpone “otherwise-unnecessary chemotherapy.”

Eltrombopag, a thrombopoietin receptor agonist, is approved by the U.S. Food and Drug Administration for use in patients with chronic primary ITP who are at an increased risk of bleeding following insufficient response to firstline therapy with corticosteroids, intravenous immunoglobulins, and anti-D immunoglobulins. “Its use in secondary ITP, as occurs in chronic lymphoproliferative disorders, has been anecdotally reported but never before systematically investigated,” corresponding author Francesco Rodeghiero, MD, also from Bortolo Hospital, told ASH Clinical News. “Our results will encourage [clinicians to use eltrombopag for] patients with lymphoproliferative disorders and low platelet counts who are at risk of bleeding or not having durable response after a short course of corticosteroids.”

In the phase II, open-label trial, a total of 18 patients with ITP secondary to chronic lymphoproliferative disorders (median age = 70 years; range = 43-83 years) were enrolled from seven Italian centers between September 2012 and November 2015. Prior to study entry, patients had an insufficient response to corticosteroids for the treatment of thrombo-

In this 24-week study, participants received eltrombopag 50 mg/day for 14 days, with dose adjustments (±25 mg/day) from week 3 to week 6. The maximum eltrombopag dose during the trial was 150 mg/day. Following study completion, patients who responded to therapy (platelet count ≥30×109/L and doubling of basal count in absence of bleeding and rescue therapy) were allowed to enter an extension phase for up to five years at physician’s discretion.

Participants had the following malignancies:

  • chronic lymphocytic leukemia (n=14)
  • classical Hodgkin lymphoma (n=2)
  • Waldenström macroglobulinemia (n=2)

The median duration of exposure to eltrombopag was 16 months (range = 1-58 months), and the median dose at weeks 4 and 24 was 50 mg (ranges = 25-150 mg).

More than three-quarters of patients (n=14) achieved a platelet response by week 4 (the study’s primary endpoint), including 14 patients with a CR (defined as a platelet count ≥100×109/L. Responses were maintained at week 24 in 59% of patients, with a CR rate of 30%.

A total of 15 patients achieved a continuous response for at least four weeks while receiving eltrombopag at doses ranging from 12.5 mg/day to 150 mg/day. Among responders, the median duration of continuous platelet response was 18 weeks (interquartile range [IQR] = 11-22 weeks), and the median duration of continuous CR was 15 weeks (IQR=4-18 weeks).

“Our results will encourage [clinicians to use eltrombopag for] patients with lymphoproliferative disorders and low platelet counts.”

—Francesco Rodeghiero, MD

Notably, the researchers wrote, “efficacy of eltrombopag in secondary ITP [was] comparable to that reported in primary ITP, with a median dosage of 50 mg … [and no] responsive patients required doses above 100 mg/day.”

During follow-up, 15 patients discontinued therapy. Reasons for discontinuation were as follows:

  • inefficacy and protocol violation (n=1)
  • loss of response (n=8)
  • death, all in responsive patients (n=3)
  • progression of lymphoproliferative disorder (n=3)

The researchers observed no grade ≥3 adverse events associated with eltrombopag treatment; however, grade 2 unprovoked iliac-femoral venous thrombosis in one patient at week 12 and grade 2 itching in another patient were reported.

Although these findings are limited by the study’s open-label design, lack of a comparator or control arm, and small number of participants, the authors suggested that eltrombopag should be considered as standard treatment in this population.

“Primary ITP in lymphoproliferative disorders, when the platelet count is <50×109/L, might induce physicians to treat the underlying disease – anticipating or restarting cytotoxic treatments, or maintaining patients on prolonged courses of corticosteroids, which can cause undue toxicity,” said Dr. Rodeghiero. “This could be substantially avoided with the use of eltrombopag.”

The study authors reported relationships with Novartis, Amgen, and Argenx.


Visco C, Rodeghiero F, Romano A, et al. Eltrombopag for immune thrombocytopenia secondary to chronic lymphoproliferative disorders: a phase 2 multicenter study. Blood. 2019 September 30. [Epub ahead of print]