This great Italian study uses eltrombopag in patients with low/intermediate risk MDS. The intervention arm had significantly fewer minor bleeding events and better platelet counts that were durable. Those with higher baseline Hb’s seemed to respond better to therapy, particularly if the Hb was >8g/dL. AML evolution/blast progression was not more common in the treatment arm, which refutes some prior concerns.
In myelodysplastic syndromes (MDS), severe thrombocytopenia is associated with poor prognosis. This multicenter trial presents the second-part long-term efficacy and safety results of eltrombopag in patients with low-risk MDS and severe thrombocytopenia.
In this single-blind, randomized, placebo-controlled, phase-II trial of adult patients with International Prognostic Scoring System low- or intermediate-1-risk MDS, patients with a stable platelet (PLT) count (<30 × 103/mm3) received eltrombopag or placebo until disease progression. Primary end points were duration of PLT response (PLT-R; calculated from the time of PLT-R to date of loss of PLT-R, defined as bleeding/PLT count <30 × 103/mm3 or last date in observation) and long-term safety and tolerability. Secondary end points included incidence and severity of bleeding, PLT transfusions, quality of life, leukemia-free survival, progression-free survival, overall survival and pharmacokinetics.
From 2011 to 2021, of 325 patients screened, 169 patients were randomly assigned oral eltrombopag (N = 112) or placebo (N = 57) at a starting dose of 50 mg once daily to maximum of 300 mg. PLT-R, with 25-week follow-up (IQR, 14-68) occurred in 47/111 (42.3%) eltrombopag patients versus 6/54 (11.1%) in placebo (odds ratio, 5.9; 95% CI, 2.3 to 14.9; P < .001). In eltrombopag patients, 12/47 (25.5%) lost the PLT-R, with cumulative thrombocytopenia relapse-free survival at 60 months of 63.6% (95% CI, 46.0 to 81.2). Clinically significant bleeding (WHO bleeding score ≥ 2) occurred less frequently in the eltrombopag arm than in the placebo group (incidence rate ratio, 0.54; 95% CI, 0.38 to 0.75; P = .0002). Although no difference in the frequency of grade 1-2 adverse events (AEs) was observed, a higher proportion of eltrombopag patients experienced grade 3-4 AEs (χ2 = 9.5, P = .002). AML evolution and/or disease progression occurred in 17% (for both) of eltrombopag and placebo patients with no difference in survival times.
Eltrombopag was effective and relatively safe in low-risk MDS with severe thrombocytopenia. This trial is registered with ClinicalTrials.gov identifier: NCT02912208 and EU Clinical Trials Register: EudraCT No. 2010-022890-33.
Benign heme article of the month– A significant portion of patients with stable platelet counts can be gently tapered from TPO-agonists. Those who needed to be re-challenged had a good response. This is likely an underutilized strategy.
Thought provoking article regarding a non-antibody mediated mechanism in chronic ITP.
New criteria for response to therapy in high grade MDS, focuses on pt centered outcomes.
Interesting prospective study assessing outcomes in ITP in pregnant women while measuring neonatal ITP in the developing child, with a control of non-pregnant women for comparison. Pregnancy-ITP was associated with a 2.7x higher rate of recurrent disease. However, bleeding was similar in pregnant vs. non-pregnant women. NITP risk was associated with more severe ITP disease in the mother and the severity of the disease, as well as prior h/o ITP in the mother.
Another new (potential) option for refractory ITP patients, efgartigimod is an IgG1-Fc-fragment engineered to reduce IgG autoantibody levels. 131 patients enrolled and 67% had >=3 prior lines of therapy, placebo controlled study. The study group had a 90% sustained platelet response, with >50% having plt counts of >30k >= 7 days apart.
FCS Hematology Oncology Review creates a platform for our physician network to observe the most recent articles and studies available in the oncology and hematology world. By sharing these articles we are building our wealth of knowledge of new observations and treatments as they come available.
