Safety of Cyclophosphamide Infusion Time Modification from 60 to 30 Minutes in Selected Chemotherapy Regimens for Lymphoma and Multiple Myeloma

Introduction/Background/Significance: Shortening chemotherapy infusion times is associated with improvements in resource use and patient satisfaction, as well as reductions in nursing workload and clinic wait times. Cyclophosphamide package inserts mention that the drug should be injected or infused very slowly, but the exact duration of infusion is not specified. Per literature review, there is heterogeneity in infusion times among regimens for various conditions.

Materials and Methods/Case Presentation/Objective: The aim was to analyze the incidence of documented adverse events (AEs) temporally related to cyclophosphamide when it was administered as either a 60- or 30-minute infusion. We performed a retrospective chart review of records between January 1, 2023, to January 31, 2024, including adult patients (age >= 18 years) who received at least one cyclophosphamide infusion over 60- or 30-minutes within selected chemotherapy regimens for lymphoma (CHOP +/- R; EPOCH +/- R; CHOEP +/- R) and multiple myeloma (MM) (CyBorD or VCD +/- Dara; KCyD +/- Dara) at any inpatient or outpatient site within the Mount Sinai Health System (MSHS).

Results/Description/Main Outcome Measures: In the lymphoma groups (34 patients with 100 doses total in  pre-implementation vs. 31 patients with 100 doses total in post-implementation), median age of patients was 57 to 63 years, with mostly male gender. Most cyclophosphamide doses were administered in the outpatient setting. The most common regimen was CHOP +/- R. Across all regimens, the median dose of cyclophosphamide was 750 mg/m2. All patients received a steroid (e.g., dexamethasone, prednisone) as part of the chemotherapy regimen. The maximum tolerated infusion rate in the pre-implementation cohort was 2,419 mg/hour and in the post-implementation cohort was 4,432 mg/hour.

In the MM groups (34 patients with 100 doses total in pre-implementation vs. 18 patients with 100 doses total in post-implementation), median age of patients was 65 to 73 years, with mostly male gender in the pre-implementation group and mostly female gender in the post-implementation group. Most cyclophosphamide doses were administered in the outpatient setting. The most common regimen was CyBorD (or VCD) +/- Dara. Across all regimens, the median dose of cyclophosphamide was 300 mg/m2. Most patients received a steroid (e.g., dexamethasone, methylprednisolone) as part of the chemotherapy regimen. Of note, 2 doses of cyclophosphamide in the pre-implementation group and 1 dose of cyclophosphamide in the post-implementation group were administered without any steroid in the chemotherapy regimen. The maximum tolerated infusion rate in the pre-implementation cohort was 690 mg/hour and in the post-implementation cohort was 1,278 mg/hour.

There were more numerical occurrences of documented Grade 1 or 2 infusion-related AEs in the 60-minute cohorts compared to 30-minutes cohorts (n = 4 vs. n = 2), and this finding was not statistically significant (2% vs. 1%; p > 0.05). There were no documented Grade 3 or higher AEs temporally related to cyclophosphamide infusion.

Conclusions: The shortening of cyclophosphamide infusion times from 60 to 30 minutes for selected chemotherapy regimens for lymphoma and MM was determined to be a safe practice change. We plan to re-evaluate infusion times for cyclophosphamide used in other disease states and regimens.