Managing Chemotherapy-Induced Thrombocytopenia: Romiplostim Research

Jodi V. Mones, MD

Our recent research demonstrates that the thrombopoietin receptor agonist romiplostim effectively modifies chemotherapy-induced thrombocytopenia (CIT) in solid tumor patients, allowing a majority to resume chemotherapy.

In the phase II study, which included 32 patients, 84 percent of those who had experienced at least four weeks of thrombocytopenia (a platelet count <100,000/mcL) had normalized platelet counts within three weeks of starting weekly treatment with romiplostim. An interim analysis of eight observation patients who all reached the primary endpoint revealed that romiplostim was conferring a significant benefit in the test group. Therefore, we discontinued the observation arm, and the trial continued to accrue volunteers as a single-arm study of romiplostim. (1)

CIT is a common complication, affecting up to 60 percent of cancer patients…the standard treatment approach has been to support those who experience a decline in platelets with transfusions as needed…or to reduce or delay future chemotherapy, risking less favorable outcomes.
Jodi V. Mones Associate Program Director, Medical Oncology/Hematology Fellowship, Hematology Track

All patients had either metastatic or locally advanced disease, and a majority, 22 patients, had gastrointestinal (GI) cancer. Twenty-five patients resumed chemotherapy after CIT correction. The mean effective romiplostim dose for platelet count correction was 2.5 mcg/kg (range 1.8 to 4.1). Only one patient had a recurrence of CIT, and four patients (12.5 percent) experienced a thrombosis, in line with reported rates in the literature for patients with metastatic GI cancers undergoing chemotherapy. The abstract was published in the journal Blood in December 2017 for the 2018 annual meeting of the American Society of Hematology. (1)

Chemotherapy-Induced Thrombocytopenia

CIT is a common complication, affecting 20 to 60 percent of patients. (2), (3) As there is no approved or validated treatment currently available for cancer patients, the standard approach has been to support cancer patients who experience a decline in platelets below 100 x 109/L with platelet transfusions as needed. Another way to manage patients with CIT is to reduce or delay future chemotherapy, risking less favorable outcomes.


Romiplostim is a man-made thrombopoietin receptor agonist (TPO mimetic) that increases platelet counts by increasing the number and maturation of bone marrow megakaryocytes. (4)It is administered by subcutaneous injection. The US Food and Drug Administration approved romiplostim (Nplate®) in 2008 for the treatment of low blood platelet counts in adults with chronic immune thrombocytopenia who have not responded to other medications or who have undergone a splenectomy. (5) In 2017, the FDA required the drug manufacturer Amgen to modify the Nplate labeling to include safety information about the risk of death and progression to acute myeloid leukemia if the drug is used in patients with myelodysplastic syndromes. (6)

Pioneering Research

Since 2010, our benign blood disorder experts have been investigating the off-label use of romiplostim in patients with active cancer. In 2014, we published a retrospective review of the first 20 patients at Memorial Sloan Kettering who received weekly romiplostim. All patients had experienced at least six weeks of persistent CIT, causing a dose reduction or the delay of ongoing chemotherapy, and they had a range of cancer types and prior chemotherapy exposure. The results were promising: All patients demonstrated a response to romiplostim and improved platelet counts. Nineteen of the 20 patients achieved a platelet count higher than the 100 x 109/L target. The mean dose that resulted in optimal correction of CIT was 2.9 mcg/kg (range 1.0 to 5.1). (7)Fifteen patients continued romiplostim throughout the resumption of chemotherapy, and none developed a recurrence of CIT. We saw no evidence of bone marrow abnormality. Three patients developed a deep vein thrombosis, consistent with what would be expected in this high-risk patient population. Finally, this case series demonstrated the efficacy of treating patients with CIT with an ongoing once per week regimen instead of a once per cycle schedule.

We also conducted a quality assessment and improvement initiative, which included 239 cancer patients at MSK who received romiplostim treatment for CIT between January 2010 and April 2017. The purpose of this project was to analyze the patients at MSK who received off-label, off-study romiplostim for CIT and evaluate the efficacy and rates of thrombosis. Of the total group, 184 patients (77 percent) had solid tumors, and 55 (23 percent) had lymphoid malignancies. We recorded platelet counts at the initiation of romiplostim and weekly after that for three weeks, and we reviewed all radiographic imaging and reports. For both the solid tumor and lymphoid malignancy groups, the mean platelet counts at least doubled by day 14. A large majority of patients tolerated the resumption of chemotherapy without a recurrence of CIT. The rate of venous thromboembolism was 11.6 percent, in line with historic rates for patients with metastatic cancer. None of the patients experienced an ischemic stroke or myocardial infarction while on the romiplostim regimen. (8) 

Phase III Clinical Research

Building on the learning from earlier stages of research, Amgen is conducting a randomized, placebo-controlled, double-blind phase III trial to study romiplostim for CIT in adult patients with GI or colorectal cancer who are receiving FOLFOX-based chemotherapy. The primary outcome measure is the incidence of either chemotherapy dose delay by four or more days, a dose reduction of 15 or more percent, or discontinuation of chemotherapy within 48 days. The study has several secondary outcome measures: platelet recovery in the absence of platelet transfusions, the depth of the platelet count nadir from the start of chemotherapy through the end of the treatment period, and the incidence of platelet transfusion, bleeding events, and adverse events within 48 days. Finally, the study is the first to include overall survival at one year as a secondary measure. The study seeks to enroll 162 patients, and recruitment is expected to open in November 2018. (9)

Hematologists at Memorial Sloan Kettering are experts in the diagnosis and management of thrombocytopenia, whether due to a side effect of cancer treatment or another cause. Our team of benign blood disorder experts includes hematologists, clinical nurses, and nurse practitioners. They collaborate with medical oncologists, radiation oncologists, surgeons, and other staff to develop a coordinated treatment plan for each patient. Our team also continues to research new strategies for preventing thrombocytopenia and other noncancerous blood disorders.

Disclosure: Dr. Gerald Soff has research support from Amgen to study romiplostim in cancer.

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  1. Soff GA, Miao Y, Devlin SM, et al. Romiplostim for Chemotherapy-Induced Thrombocytopenia (CIT). Results of a Phase 2 Trial. Blood. 2017;130(Suppl 1), 289.
  2. Ten Berg MJ, van den Bernt PM, Shantakumar S, et al. Thrombocytopenia in adult cancer patients receiving cytotoxic chemotherapy: results from a retrospective hospital-based cohort study. Drug Saf. 2011;34(12):1151-60.
  3. Yu J, et al. Clinical studies of recombinant human thrombopoietin in treatment of gemzar and cisplatin-induced thrombocytopenia in patients with non-small cell lung cancer. Chin J Cancer Prevention and Treatment. 2009;16(5):374-376.
  4. Kuter DJ. Biology and chemistry of thrombopoietic agents. Semin Hematol. 2010;47(3):243–248.
  5. FDA approval letter for romiplostin. Centre for Drug Evaluation and Research. August 2008.
  6. Letter: supplemental biologics license application for Nplate (romiplostim) injection, 250 mcg, 500 mcg vial (500 mcg/mL). Drugs@FDA: FDA Approved Products. June 2017.
  7. Parmameswaran R, Lunning M, Mantha S, et al. Romiplostim for management of chemotherapy-induced thrombocytopenia. Support Care Cancer. 2014;22(5):1217-1222.
  8. Li VJ, Miao Y, Wilkins C, Soff GA. Efficacy and thrombotic adverse events of romiplostim use in patients with thrombocytopenia related to underlying malignancies. Oral Presentation. Sept 2017. 
  9. Study of romiplostim for chemo-induced thrombocytopenia in adult subjects with gastrointestinal or colorectal cancer. Accessed on June 12, 2018.