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Ferrata Storti Foundation
Haematologica 2021 Volume 106(4):1148-1157
Platelet Biology & its Disorders
A multicenter study of romiplostim for chemotherapy-induced thrombocytopenia in solid tumors and hematologic malignancies
Hanny Al-Samkari,1,2 Aric D. Parnes,2,3,4 Katayoon Goodarzi,1,2 James I. Weitzman,2,5 Jean M. Connors2,3,4 and David J. Kuter1,2
1Division of Hematology Oncology, Massachusetts General Hospital, Boston, MA; 2Harvard Medical School, Boston, MA; 3Hematology Division, Brigham and Women’s Hospital, Boston, MA; 4Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA and 5Division of Hematology Oncology, Newton-Wellesley Hospital, Newton, MA, USA
ABSTRACT
Chemotherapy-induced thrombocytopenia (CIT) frequently compli- cates cancer treatment causing chemotherapy treatment delays, dose reductions, and discontinuation. There is no US Food and Drug Administration (FDA)-approved agent available to manage CIT. This study retrospectively evaluated patients with CIT treated on institutional romi- plostim treatment pathways at four US centers. The primary outcome was achievement of a romiplostim response (median on-romiplostim platelet count ≥75x109/L and ≥30x109/L above baseline). Secondary outcomes includ- ed time to platelet count ≥100x109/L and rates of the following: platelet count <100×109/L, platelet count <75x109/L, platelet count <50x109/L, thrombocytosis, chemotherapy dose reduction/treatment delay, platelet transfusion, bleeding, and thromboembolism. Multivariable regression was used to identify predictors of romiplostim non-response and compare week- ly dosing with intracycle/intermittent dosing. A total of 173 patients (153 solid tumor, 20 lymphoma or myeloma) were treated, with 170 (98%) receiving a median of four (range: 1-36) additional chemotherapy cycles on romiplostim. Romiplostim was effective in solid tumor patients: 71% of patients achieved a romiplostim response, 79% avoided chemotherapy dose reductions/treatment delays, and 89% avoided platelet transfusions. Median per-patient platelet count on romiplostim was significantly higher than base- line (116x109/L vs. 60x109/L; P<0.001). Bone marrow (BM) tumor invasion, prior pelvic irradiation, and prior temozolomide exposure predicted romi- plostim non-response. Bleeding rates were lower than historical CIT cohorts and thrombosis rates were not elevated. Weekly dosing was superior to intracycle dosing with higher response rates and less chemotherapy dose reductions/treatment delays/bleeding; intracycle dosing had an incidence rate ratio (IRR) for dose reduction/treatment delay of 3.00 (95%CI: 1.30- 6.91; P=0.010) and an IRR for bleeding of 4.84 (95%CI: 1.18-19.89, P=0.029) compared with weekly dosing. Blunted response (10% response rate) was seen in non-myeloid hematologic malignancy patients with BM involve- ment. In conclusion, romiplostim was safe and effective for CIT in most solid tumor patients.
Introduction
Thrombocytopenia is frequent in cancer patients, usually due to myelosuppres- sive chemotherapy, tumor infiltration of the bone marrow (BM), or infection.1 Chemotherapy-induced thrombocytopenia (CIT) is a common complication of cytotoxic chemotherapy and many targeted therapies, occurring in approximately 15-25% of patients receiving platinum, taxane, and/or gemcitabine-based regimens.2 Currently there is no US Food and Drug Administration (FDA)-approved agent for CIT management. Platelet transfusion offers only temporary, unreliable
Correspondence:
HANNY AL-SAMKARI
hal-samkari@mgh.harvard.edu
Received: March 5, 2020. Accepted: May 27, 2020. Pre-published: June 4, 2020.
https://doi.org/10.3324/haematol.2020.251900
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