Romiplostim Improves Platelet Counts, Chemotherapy Adherence in Patients With Chemotherapy-Induced Thrombocytopenia

Patients with cancer who develop chemotherapy-induced thrombocytopenia (CIT) often require delays, reductions, or discontinuations of treatment, but romiplostim appeared to allow patients to stay on chemotherapy, while also improving their platelet counts, according to results from a study presented at the 2019 ASH Annual Meeting. Romiplostim had the greatest effect in patients with solid tumor cancers and CIT and showed modest efficacy in those with lymphoid malignancies and underlying bone marrow involvement, lead investigator Hanny Al-Samkari, MD, from Harvard Medical School and Massachusetts General Hospital, noted during his presentation.

Dr. Al-Samkari shared findings from the first large multicenter study of romiplostim for CIT. Researchers retrospectively collected data on romiplostim dosing, chemotherapy, platelet counts, and response to romiplostim in patients with either lymphoid malignancies or solid tumor cancers who developed CIT and received romiplostim between 2009 and 2019. Response was defined as achieving a median platelet count of ≥75×109/L and at least 30×109/L higher than baseline, on romiplostim.

A total of 173 patients, including 153 with solid tumor cancers and 20 with lymphoid malignancies (13 with lymphoma and 7 with myeloma), were included in this analysis. The median age was 60 years (range = 19-85 years), and 45% of participants were female. At baseline, 75% of patients had metastatic cancer and 50% had hepatic involvement by tumor.

Patients had a median of two prior chemotherapy regimens (range = 1-11), and 79% previously required a dose reduction or delay in chemotherapy due to their CIT, with a median duration of delay of three weeks (range = 1-15 weeks).

Patients received a median starting romiplostim dose of 3 µg/kg per week, which also was identified as the “optimized” median dose at which patients achieved a platelet count >100×109/L. Seventy-three patients received intracycle romiplostim (twice monthly on average) during chemotherapy off-weeks, while 80 received standard weekly dosing.

Treatment with romiplostim led to significantly higher median per-patient platelet counts, compared with baseline:

  • all patients: 112×109/L vs. 54×109/L (p<0.001)
  • solid tumor patients: 116×109/L vs. 60×109/L (p<0.001)

In the entire study population, 170 (98%) were able to receive a median of four additional chemotherapy cycles (range = 1-36) over a median of 10 weeks of romiplostim treatment (range = 2-125 weeks).

When the investigators compared the outcomes of different romiplostim dosing schedules, they found that weekly dosing of romiplostim led to better outcomes, compared with intracycle dosing, including higher median platelet counts (143×109/L vs. 106×109/L; p value not reported) and response rates (81% vs. 63%; p=0.006). Intracycle dosing also was associated with higher rates of chemotherapy intensity reduction (rate ratio [RR] = 3.00; 95% CI 1.30-6.91; p=0.010), bleeding (RR=4.84; 95% CI 1.18-19.89; p=0.029), and platelet counts <50, <75, or <100×109/L.

Both dosing schedules had similar safety, though, Dr. Al-Samkari reported. Bleeding occurred in 7.5% of patients, and venous thromboembolism (VTE) in 4.6%, during treatment with romiplostim. “VTE rates were similar to comparable cancer populations not receiving romiplostim,” he noted.

While romiplostim treatment showed high efficacy in patients with solid tumor cancers, it appeared to have only “modest efficacy” in those with hematologic malignancies. Just 35% of patients with myeloma or lymphoma received more than one additional chemotherapy cycle on romiplostim. Platelet responses also were smaller:  Patients with myeloma had a median platelet increase from 19×109/L at baseline to 39×109/L after romiplostim treatment (p=0.078), while patients with aggressive lymphoma had an increase from 23×109/L to 47×109/L (p=0.033). The lack of benefit could be explained by the presence of extensive underlying bone marrow involvement and the use of weekly dosing in this group.

“Additional studies are required to evaluate romiplostim to treat CIT in lymphoma without bone marrow involvement,” Dr. Al-Samkari noted. Other factors predicting a lack of response to romiplostim across the entire study population included pelvic irradiation, bone marrow invasion, and having received prior temozolomide, he added.

Limitations of the study include its lack of a control group and the low number of patients with lymphoid malignancies.

The authors report no relevant conflicts of interest.  

Reference

Al-Samkari H, Parnes AD, Goodarzi K, et al. A Multicenter Study of Romiplostim to Treat Chemotherapy-Induced Thrombocytopenia in Solid Tumors and Lymphoid Malignancies. Abstract #389. Presented at the 2019 ASH Annual Meeting, December 8, 2019; Orlando, FL.

SHARE