TPO concentrations and response to romiplostim
Authors: David J. Kuter, Anne Meibohm, Angela Lopez
Journal: American Journal of Hematology (2014)

To the Editor: A recent analysis of thrombopoietin (TPO) concentrations in thrombocytopenias by Makar et al. 1 found that these concentrations could differentiate between patients with consumptive thrombocytopenia (e.g., immune thrombocytopenia [ITP]) as compared with hypoproliferative thrombocytopenia (e.g., bone marrow failure or chemotherapy-related thrombocytopenia). Examination of endogenous TPO (eTPO) concentrations in patients with primary or secondary ITP (N = 36) found that they were not associated with disease duration or whether patients were receiving treatment. However, there was an association between eTPO concentrations >95 pg/mL and lack of response in ITP patients receiving the TPO receptor agonists romiplostim or eltrombopag (N = 21, P < 0.002), with response defined as maintaining a platelet count ≥50 × 109/L for ≥50% of the time without need for rescue therapy until TPO receptor agonist discontinuation, loss to follow-up, or 3 months, whichever was longest. We, therefore, sought to examine whether a similar relationship could be found in ITP patients treated with romiplostim in the two major trials (both described in 2). In the two 24-week trials, 83 patients (42 splenectomized) received romiplostim; these patients were evaluated for durable response (platelet count ≥50 × 109/L during ≥6 of the last 8 weeks of treatment) and overall response (having a durable response or a transient response [≥4 weekly platelet responses from weeks 2–24]). When durable and overall response rates were evaluated using baseline eTPO concentration thresholds of 100, 150, and 175 pg/mL, there was a tendency for patients with lower eTPO concentrations to be more likely to respond, but the relationship was not consistent and often was not statistically significant. We next used the response measure in Makar et al. (here called “clinical response”) to further examine this data. Using a model adjusted for splenectomy status, baseline platelet count, and ITP duration, the adjusted odds ratios for every 10 pg/mL increase in baseline eTPO concentrations affecting durable, overall, or clinical platelet response measures were 0.953, 0.934, and 0.930, respectively, (Table 1). Thus, we can conclude that while the likelihood of response decreases slightly with higher baseline eTPO concentrations, this relationship is not statistically significant. Furthermore, there was no obvious threshold concentration at which a significant change in likelihood of response was observed. While at first glance these results are not completely in line with the findings of Makar et al., it is worth noting that of the five ITP patients with higher baseline eTPO concentrations (>95 pg/mL) who did not respond to TPO receptor agonists in that analysis, one was subsequently discovered to have amegakaryocytic thrombocytopenia refractory to multiple therapies and three others were also unresponsive to multiple therapies. Therefore, it is possible that the utility of measuring eTPO concentrations is more to validate a diagnosis of typical ITP as compared with atypical ITP or some other consumptive thrombocytopenia rather than to predict response to treatment with a TPO receptor agonist. David J. Kuter,1 Anne Meibohm,2 and Angela Lopez2 1Department of Hematology, Massachusetts General Hospital, Yawkey 7940, 55 Fruit Street, Boston, Massachusetts 2Department of Biostatistics, Amgen, One Amgen Center Drive, Thousand Oaks, CA 91320