Romiplostim in chemotherapy-induced thrombocytopenia: A review of the literature

Abstract

Chemotherapy-induced thrombocytopenia (CIT) is a common challenge of cancer therapy and can lead to chemotherapy dose reduction, delay, and/or discontinuation, affecting relative dose intensity, and possibly adversely impacting cancer care. Besides changing anticancer regimens, standard management of CIT has been limited to platelet transfusions and supportive care. Use of the thrombopoietin receptor agonist romiplostim, already approved for use in immune thrombocytopenia, has shown promising signs of efficacy in CIT. In a phase 2 prospective randomized study of solid tumor patients with platelet counts <100 × 10⁹/L for ≥4 weeks due to CIT, weekly romiplostim corrected the platelet count to >100 × 10⁹/L in 93% (14/15) of patients within 3 weeks versus 12.5% (1/8) of untreated patients (p < 0.001). Including patients treated with romiplostim in an additional single-arm cohort, 85% (44/52) of all romiplostim-treated patients responded with platelet count correction within 3 weeks. Several retrospective studies of CIT have also shown responses to weekly romiplostim, with the largest study finding that poor response to romiplostim was predicted by tumor invasion of the bone marrow (odds ratio, 0.029; 95% CI: 0.0046-0.18; p < 0.001), prior pelvic irradiation (odds ratio, 0.078; 95% CI: 0.0062-0.98; p = 0.048), and prior temozolomide treatment (odds ratio 0.24; 95% CI: 0.061-0.96; p = 0.043). Elsewhere, lower baseline TPO levels were predictive of romiplostim response (p = 0.036). No new safety signals have emerged from romiplostim CIT studies. Recent treatment guidelines, including those from the National Comprehensive Cancer Network, now support consideration of romiplostim use in CIT. Data are expected from two ongoing phase 3 romiplostim CIT trials.

Keywords: chemotherapy; peptibody; platelet growth factors; romiplostim; thrombocytopenia; thrombopoietin receptor agonists.

FIGURE 1

Platelet production and destruction pathways– effect of various anticancer therapies. BH3, Bcl‐2 homology 3; CAR‐T, chimeric antigen receptor T; CTLA, cytotoxic T‐lymphocyte antigen; HSC, hematopoietic stem cell; MK‐CFC, megakaryocyte colony‐forming cell; NF‐κB, nuclear factor kappa B; PD‐1, programmed cell death protein 1; PD‐L1, programmed cell death ligand 1.

FIGURE 2

(A) Romiplostim structure. (B) Romiplostim signaling and platelet production. eTPO, endogenous thrombopoietin; JAK, Janus kinase; STAT, signal transducer and activator of transcription; TPO‐R, thrombopoietin receptor. This figure was adapted from a review on romiplostim.