Incidence of neutropenia with intrathecal pemetrexed for leptomeningeal disease associated with solid tumors – A retrospective analysis
Nicholas D Ngo, Anshika Singh, Scott Hampton, David E Piccioni, Sandip P PatelBackground
Leptomeningeal disease is a complication of advanced solid tumors, and treatment options are limited by inadequate central nervous system penetration. Intrathecal pemetrexed has emerged as an off-label therapeutic option. However, data describing its hematologic toxicity, particularly neutropenia, are limited.
Objective
To evaluate the incidence, timing, and severity of neutropenia associated with intrathecal pemetrexed and to assess differences in neutropenia risk among clinically relevant subgroups, such as concomitant osimertinib use, vitamin supplementation, and exposure to other bone marrow suppressing medications.
Methods
A retrospective analysis was conducted of adult patients who received at least one dose of intrathecal pemetrexed over a four-year period. Patient demographics, treatment characteristics, laboratory values, concomitant therapies, and history of prior craniospinal irradiation were extracted from the electronic health record. The primary outcome was incidence of neutropenia, defined as an absolute neutrophil count <1.0 × 10 9 /L. Exploratory subgroup analyses evaluated neutropenia incidence and severity based on concomitant osimertinib therapy, vitamin supplementation status, and use of other medications with bone marrow suppressing potential.
Results
Sixteen patients who received 138 doses were included. Neutropenia occurred in approximately one-third of patients, most commonly after loading doses. Higher neutropenia incidence and earlier onset were observed in patients receiving concomitant osimertinib and those not receiving vitamin B12 and folic acid supplementation. No consistent increase in neutropenia was observed with other marrow-suppressing medications.
Conclusion
Intrathecal pemetrexed is associated with clinically meaningful neutropenia. Subgroup findings highlight the importance of vitamin supplementation, careful regimen assessment, and close hematologic monitoring to optimize safety and patient outcomes.