The International Society on Thrombosis and Haemostasis (ISTH) has issued first guidance on the use of thrombopoietin receptor agonists (TPO-RAs) for chemotherapy-induced thrombocytopenia (CIT), amid a lack of high-quality clinical evidence in this clinical setting.
Dr Hanny Al-Samkari, co-author of the CIT guidelines and Haematologist at Massachusetts General Hospital, told the limbic that the recommendations are based on the latest available data and will help clinicians in haematology and oncology provide evidence-based care for this important and often overlooked complication of cancer therapy.
CIT occurs in around 33% of patients with solid tumours and 50% of those with a haematological malignancy. Platelet transfusions are the current mainstay treatment, but provide only a short and unpredictable level of improvement, noted experts from the ISTH Subcommittee on Haemostasis & Malignancy, highlighting the unmet clinical need in this area.
“CIT may complicate the administration of chemotherapy leading to therapeutic delays or dose reductions,” they noted.
Four TPO-RAs are approved in the USA and in Europe for at least one thrombocytopenic state including immune thrombocytopenia. However, while clinical evidence has shown that they improve platelet counts for patients with CIT, none have thus far been approved specifically for this indication.
As such, ISTH experts developed consensus guidance statements and recommendations based on a review of 440 articles on the TPO-RAs romiplostim, eltrombopag, avatrombopag, and lusutrombopag in the treatment or prevention of CIT, published in the Journal of Thrombosis and Haemostasis (link here).
“Studies have shown that TPO-RAs can improve platelet counts in CIT, but the clinical benefits of TPO-RA in terms of reducing bleeding, limiting platelet transfusion, or avoiding chemotherapy delay or dose reduction are uncertain,” the authors said..
The guidance recommends empirical platelet transfusions for patients with platelet counts of less than 10 × 109 per L, and for those with serious bleeding (WHO grade 2 or higher) and platelet counts of less than 50 × 109 per L. Prophylactic platelet transfusions are not recommended.
Clinicians who are considering use of TPO-RAs for CIT should in the first instance seek to enrol their patient in a clinical trial, given that to date there has been only one Phase III trial reported relating to their efficacy in this clinical setting, the experts noted.
If trial enrolment is not possible, TPO-RAs should be considered in the setting of inadequate platelet recovery on day 1 of a chemotherapy cycle to avoid chemotherapy dose reductions or delays, which can negatively impact cancer outcomes.
Once initiated, the TPO-RA should be continued for the duration of chemotherapy using the lowest dose to maintain a platelet count between 100–200 × 109 per L.
Romiplostim preferred
If a TPO-RA is being considered outside of a clinical trial setting, romiplostim is recommended over other TPO-RAs as the published evidence with this therapeutic does suggest efficacy.
However, the guidance recommends against the use of TPO-RAs for CIT for patients with acute myeloid leukaemia, because activation of the TPO receptor “could stimulate some myeloid leukaemic cells leading to a worse cancer outcome”, and in patients with high-risk myelodysplasia, as clinical evidence indicates a lack of efficacy on platelet recovery, potentially fatal drug-related events, and worse survival.
The ISTH also advised against use of TPO-RA’s for patients with lymphoma or those undergoing post-haematopoietic stem cell transplantation outside of a clinical trial, due to a lack of evidence on efficacy in these settings.
It did not recommend prophylactic tranexamic acid to prevent bleeding in patients with CIT, after a multicenter, randomised clinical trial of the treatment versus placebo (in addition to standard platelet transfusion) in patients being treated for haematologic malignancies had no significant impact on bleeding, the mean number of platelet transfusions, or thrombotic events.
According to Dr Al-Samkari, the recommendations are “highly relevant for clinical practice in the USA, Europe, and globally, given how common chemotherapy-induced thrombocytopenia is worldwide and how it can negatively impact the patient’s oncologic care and safety.”
“Ultimately, however, ongoing pivotal phase 3 trials and other important clinical trials will be critical in filling the gaps in knowledge in the management of chemotherapy-induced thrombocytopenia,” he said.
Randomised trials of romiplostim and avatrombopag are currently ongoing and have the potential to set a clearer and more definitive standard of care in the management of chemotherapy-induced thrombocytopenia, the guideline authors concluded.