Elissa Engel, MD
Eltrombopag (Promacta) boosted the platelet count in a 13-year-old boy with HIV-associated thrombocytopenia, according to case study results presented at the 2018 American Society of Pediatric Hematology/Oncology Conference (ASPHO), held May 2-5 in Pittsburgh, Pennsylvania.1
The findings are important because thrombocytopenia is a common hematologic event in pediatric HIV.
“After initiation of this mediation at 50 mg per day, [the child] showed a sustained improvement in his platelet count and has so far been free of symptomatic thrombocytopenia,” lead author Elissa Engel, MD, a second-year pediatric resident at the University of South Florida (USF), told OncLive®
The patient had previously failed on first-line treatment with IV immunoglobin and antiretroviral optimization.
The FDA approved oral eltrombopag, a thrombopoietin receptor agonist that stimulates bone marrow megakaryocytes to produce platelets, in November 2008 for treatment of thrombocytopenia in patients with idiopathic thrombocytopenic purpura who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.
Thrombocytopenia was observed in 29 (8.5%) of 339 children with HIV in a 14-year study that evaluated for prevalence of the condition.2
Chronic and acute thrombocytopenia were observed in 22 and 7 children, respectively.
At ASPHO, Engel delivered the findings of a retrospective chart review in a poster. The patient in question was diagnosed with HIV after he experienced several incidents of thrush. At baseline, his white blood cell count was 1500 with a CD4 T cell count <1%. His HIV viral load was >50,000 copies/mL and he had a platelet count of 18,000.
His viral load was undetectable after 3 months of antiretroviral treatment with lamivudine/zidovudine (Combivir) and Iopinavir/ritonavir (Kaletra), but physicians were unable to resolve his thrombocytopenia. Physicians switched him to a combination of dolutegravir (Tivicay), abacavir (Ziagen), and emtricitabine (Emtriva) because that regimen has been associated with a lower incidence of thrombocytopenia.
The patient received infusions of IV immunoglobin on a near-monthly basis, but his response was short-lived and the treatment reduced his quality of life.
Physicians then initiated 50 mg of daily eltrombopag in hopes of maintaining a platelet count ≥10,000. The patient achieved a sustained platelet count of 32,000 to 88,000 with no significant adverse events (AEs).
Eltrombopag is rarely prescribed for pediatric patients because the drug has a black box warning for hepatotoxicity, Engel explained. When used in combination with interferon and ribavirin, eltrombopag has been associated with increased risk for hepatotoxicity, which can aggravate underlying cardiopulmonary disease and increase the risk for death.3
Physicians at USF decided to move forward with eltrombopag based on results from the PETIT and PETIT2 trials involving children with persistent and chronic immune thrombocytopenia.4,5
PETIT was a 3-part, randomized, multicenter, placebo-controlled study trial conducted at 22 medical centers. Investigators recruited patients aged 1 to 17 years with immune thrombocytopenia lasting ≥6 months and platelet count less than 30 × 109
/L who were relapsed/refractory to at least 1 previous treatment or who were ineligible for other treatments because of a medical disorder.
Part 1 was a dose-finding phase in which patients received open-label eltrombopag for 24 weeks. In the double-blind part 2, patients were randomly assigned to eltrombopag or placebo for 7 weeks. Part 2 included additional patients not treated in the dose-finding phase.
In the open-label part 3, patients who previously received eltrombopag stayed on-treatment for 17 additional weeks while those who had previously received placebo were assigned to 24 weeks of eltrombopag.
The proportion of patients who had a platelet count of ≥50 × 109
/ L at least once during weeks 1 to 6 of the randomized phase of the study without rescue therapy was the primary endpoint. Forty-five patients were assigned to eltrombopag and 22 were assigned to placebo.
During part 2, 62% (n = 28) of patients assigned to eltrombopag achieved the primary endpoint compared with 32% (7) of those assigned to placebo (odds ratio [OR], 4.31, 95% CI, 1.39-13.34, P
= .011). Thirteen patients (29%) assigned to eltrombopag maintained responses through week 6 compared with only 1 (5%) patient in the placebo group. Eleven (24%) patients in eltrombopag group had a continuous response for more than 3 weeks compared with zero patients assigned to placebo, according to post-hoc analysis.