# Romiplostim for Prevention of Severe Chemotherapy-Induced Thrombocytopenia in Lymphoma Patients—Phase I Study

## TL;DR

This study shows romiplostim can help prevent severe low platelet counts in lymphoma patients undergoing chemotherapy, reducing transfusion needs and treatment delays.

## Contribution

The study introduces romiplostim as a promising secondary prophylactic agent for chemotherapy-induced thrombocytopenia in lymphoma patients.

## Key findings

- Romiplostim prevented grade 4 thrombocytopenia in 47% of chemotherapy cycles.
- Platelet transfusion requirements were reduced in 65% of cycles.
- Low starting doses were ineffective in preventing recurrent thrombocytopenia.

## Abstract

Lymphoma patients receiving intensive chemotherapy frequently develop severe chemotherapy-induced thrombocytopenia, characterized by critically low platelets that increase bleeding risk, necessitate platelet transfusions, and often force treatment delays or dose reductions. While pharmacologic growth factors are routinely used to manage chemotherapy-induced neutropenia, thrombopoietic agents remain inadequately studied. This phase I study investigated whether secondary prophylaxis with weekly romiplostim administration could prevent recurrent severe thrombocytopenia in lymphoma patients undergoing chemotherapy who had already experienced profound platelet drops requiring transfusions in prior cycles. Nine patients were enrolled across three dose schedules to establish a recommended phase 2 dose schedule. Romiplostim effectively prevented grade 4 thrombocytopenia in nearly half of the chemotherapy cycles and substantially reduced platelet transfusion requirements in this high-risk population. The agent was well-tolerated without thromboembolic complications, enabling most patients to maintain their planned chemotherapy schedule at full dose intensity. These findings establish a dosing framework and suggest that secondary prophylaxis with romiplostim may represent a viable strategy to optimize chemotherapy delivery in lymphoma patients.

Background/Objectives: Intensive chemotherapy is the cornerstone of lymphoma treatment but often leads to severe chemotherapy-induced thrombocytopenia (sCIT), resulting in treatment delays, reduced dose intensity, and the need for transfusions. While granulocyte colony-stimulating factors (G-CSFs) are commonly used to manage neutropenia, the use of thrombopoietic growth factors has not been adequately studied. Methods: This phase I dose-finding study evaluated the use of weekly romiplostim as prophylaxis for recurrent sCIT in patients undergoing chemotherapy for lymphoma. Eligible patients were those treated with a 21-day chemotherapy cycle who previously experienced sCIT, thus serving as their own “controls”. sCIT was defined as one of the following: (A) a platelet count (PLT) <50 × 109/L on day 1 of the subsequent cycle, leading to delay or dose reduction in chemotherapy, or (B) grade 4 thrombocytopenia (<25 × 109/L) and/or (C) platelet transfusion for bleeding. The primary endpoints were the incidence of sCIT and the rate of romiplostim-associated-adverse-events, with thromboembolic complications being an event of special interest. Results: Nine patients with sCIT requiring a PLT transfusion on the prior treatment cycle were treated across three dose schedules. The phase 2 recommended schedule was defined as a starting dose of 3–5 mcg/kg based on the baseline PLT count, with weekly adjustments for counts <150 × 109/L and >450 × 109/L. Romiplostim prevented recurrent grade 4 thrombocytopenia in 47% of the chemotherapy cycles and averted recurrent transfusion in 65% of cycles. Notably, low starting doses, as used in solid malignancies, were insufficient, leading to recurrent thrombocytopenia. Conclusions: Romiplostim was well-tolerated, with no thromboembolic events, and allowed most patients to complete their chemotherapy on schedule at full dose intensity.