Monotherapy with Romiplostim Is Comparable to Combination with Short-Acting Platelet- Elevating Therapy in Platelet Recovery for Chemotherapy-Induced Thrombocytopenia (CTIT): A Retrospective Clinical Study

Technical Summary: Monotherapy with Romiplostim vs. Combination Therapy for CTIT

Problem Statement
Chemotherapy-induced thrombocytopenia (CTIT) is a frequent complication of antineoplastic treatments that suppresses bone marrow megakaryocytes, leading to decreased platelet production and increased bleeding risks. CTIT often necessitates chemotherapy dose reductions, treatment delays, or interruptions, adversely affecting patient prognosis and increasing medical costs. While short-acting platelet-elevating agents (such as recombinant human thrombopoietin [rhTPO], interleukin-11 [IL-11], and short-acting TPO receptor agonists) are commonly used to achieve rapid platelet increases, they often require daily administration and have limitations regarding stability and tolerability. Romiplostim, a long-acting TPO receptor agonist (TPO-RA) administered weekly, has shown efficacy in CTIT. However, clinical practice frequently employs a combination of romiplostim with short-acting agents in an attempt to achieve "faster and higher" platelet recovery. There is currently a lack of definitive evidence regarding whether this combination therapy offers superior efficacy or safety compared to romiplostim monotherapy.

Methodology
This was a retrospective, single-center clinical study conducted at Nanjing Second Hospital between May 2024 and January 2026. The study enrolled 79 patients (aged ≥18) with malignant solid tumors or non-myeloid hematologic malignancies who developed CTIT (baseline platelet count <50×10⁹/L) following antitumor therapy. Patients were divided into two groups based on their treatment regimen:

1. Monotherapy Group (n=38): Received romiplostim alone (starting dose 3 µg/kg, weekly subcutaneous injection, adjustable up to 10 µg/kg).
2. Combination Group (n=41): Received romiplostim concurrently with short-acting platelet-elevating agents, including IL-11, rhTPO, or short-acting TPO-RAs (eltrombopag or hetrombopag).

Treatment in both groups was discontinued when platelet counts recovered to >75×10⁹/L or increased by ≥30×10⁹/L from baseline. The study utilized SPSS Statistics 26.0 for analysis, comparing groups using t-tests, Wilcoxon signed-rank tests, and chi-square tests. Key efficacy endpoints included the Objective Response Rate (ORR), time to platelet recovery, and chemotherapy modification rates. Safety endpoints included bleeding incidence, thromboembolism, platelet transfusion rates, and adverse events.

Key Contributions and Results
The study provides comparative data on the efficacy and safety of romiplostim monotherapy versus combination therapy in a real-world CTIT setting.

• Efficacy: No statistically significant differences were observed between the two groups in the primary endpoints.
  • Objective Response Rate (ORR): 61.5% in the monotherapy group vs. 65% in the combination group (P=0.750).
  • Time to Platelet Recovery: The median time was 10.5 days for monotherapy vs. 15.5 days for combination therapy (P=0.299).
  • Chemotherapy Modification: Rates were comparable (34.2% vs. 41.4%, P=0.507).
  • Subgroup Analysis: Consistent efficacy trends were observed across both hematologic malignancies and solid tumors, with significant platelet count increases in all subgroups regardless of treatment arm.
• Safety: Safety profiles were comparable between the groups.
  • Bleeding Incidence: 21.1% (monotherapy) vs. 7.3% (combination), P=0.143.
  • Thromboembolism: 0% (monotherapy) vs. 2.4% (combination), P=0.333.
  • Platelet Transfusion Rate: 50% (monotherapy) vs. 63.4% (combination), P=0.229.
  • Adverse events in the monotherapy group were generally mild (e.g., musculoskeletal pain, dizziness). No significant changes in liver or kidney function were observed in either group.

Significance and Claims
The paper concludes that adding short-acting platelet-elevating agents to romiplostim does not significantly improve platelet recovery outcomes compared to romiplostim monotherapy for CTIT. The authors claim that the two regimens are comparable in both efficacy and safety.

Based on these findings, the study suggests that romiplostim monotherapy is a viable, effective, and convenient treatment option for CTIT. The authors highlight several practical advantages of monotherapy over combination therapy:

1. Cost-Effectiveness: Monotherapy avoids the substantial additional costs associated with combining multiple agents, which is significant for patients requiring long-term treatment across multiple chemotherapy cycles.
2. Convenience: Monotherapy involves a once-weekly injection, whereas combination regimens often require daily injections of short-acting agents, reducing the burden on patients with limited mobility or those requiring frequent hospital visits.
3. Safety: Monotherapy avoids the potential for additive adverse effects associated with combination therapies (e.g., increased risk of thrombosis or fever with IL-11).

The authors attribute the lack of synergistic effect in combination therapy to potential "receptor saturation" of the thrombopoietin receptor (c-Mpl) by romiplostim, which may prevent subsequent binding of short-acting agents. While acknowledging limitations such as the retrospective design, small sample size, and inherent selection bias (particularly the higher proportion of hematologic malignancy patients in the monotherapy group), the study posits that for the majority of CTIT patients, monotherapy should be considered a preferred strategy. The authors note that combination therapy may still warrant evaluation in specific refractory cases, but current high-level evidence does not strongly support its routine use over monotherapy.