Romiplostim Treatment of Chemotherapy-Induced Thrombocytopenia

Abstract

Purpose: Chemotherapy-induced thrombocytopenia (CIT) leads to delay or reduction in cancer treatment. There is no approved treatment.

Methods: We conducted a phase II randomized trial of romiplostim versus untreated observation in patients with solid tumors with CIT. Before enrollment, patients had platelets less than 100,000/μL for at least 4 weeks, despite delay or dose reduction of chemotherapy. Patients received weekly titrated romiplostim with a target platelet count of 100,000/μL or more, or were monitored with usual care. The primary end point was correction of platelet count within 3 weeks. Twenty-three patients were treated in a randomization phase, and an additional 37 patients were treated in a single-arm, romiplostim phase. Resumption of chemotherapy without recurrent CIT was a secondary end point.

Results: The mean platelet count at enrollment was 62,000/μL. In the randomization phase, 14 of 15 romiplostim-treated patients (93%) experienced correction of their platelet count within 3 weeks, compared with one of eight control patients (12.5%; P < .001). Including all romiplostim-treated patients (N = 52), the mean platelet count at 2 weeks of treatment was 141,000/μL. The mean platelet count in the eight observation patients at 3 weeks was 57,000/μL. Forty-four patients who achieved platelet correction with romiplostim resumed chemotherapy with weekly romiplostim. Only three patients (6.8%) experienced recurrent reduction or delay of chemotherapy because of isolated CIT.

Conclusion: This prospective trial evaluated treatment of CIT with romiplostim. Romiplostim is effective in correcting CIT, and maintenance allows for resumption of chemotherapy without recurrence of CIT in most patients.

Trial registration: ClinicalTrials.gov NCT02052882.

FIG 1.

Platelet counts before enrollment. Counts are mean and 95% CI.

FIG 2.

Platelet counts and relative dose intensity of chemotherapy in a representative patient before and during romiplostim treatment. Patient No. 12 was a 29-year-old man with metastatic colon cancer involving the liver and lungs. Before enrollment, he experienced chemotherapy-induced thrombocytopenia despite reduction in doses and delay of fluorouracil and irinotecan. His platelet count improved from 55,000 to 135,000 per μL after 1 week of romiplostim treatment, and he resumed full-dose fluorouracil and irinotecan without recurrent chemotherapy-induced thrombocytopenia for 34 months while receiving treatment. At 3 years of romiplostim treatment with ongoing chemotherapy, he died as a result of his cancer. IVCI, continuous infusion.

FIG 3.

Platelet counts during the trial, 0 to 6 weeks; counts are mean and 95% CI. These results are for all romiplostim-treated patients, including those in the randomization phase as well as the single-arm phase. The platelet counts of romiplostim-treated and observation-control patients diverged by 1 week, and the differences persisted for 3 weeks, through the primary end point. Once the control patients crossed over to romiplostim, their platelet counts increased at a rate similar to romiplostim upfront.