Background: The DEFeNDR (Decreasing the burden of Febrile Neutropenia through Dynamic RPM) program leverages in-home technology and centralized nurse monitoring to facilitate ambulatory management as an alternative to hospital-based care for cancer patients with neutropenic fever (NF). The objective of this study is to assess 30-day care utilization outcomes and patient satisfaction at 12 months after program implementation. Methods: Adult cancer patients hospitalized with NF were assessed daily for DEFeNDR program eligibility including MASCC score ≥21 (per ASCO guidelines) and no cellular therapy (CAR-T, BMT) in the prior 100 days. Patients agreeing to participate in the 30-day program received a cellular-enabled tablet with pre-connected devices for twice-daily vital signs and symptom assessments. Patient generated data were EHR-integrated in real-time. Embedded decision trees facilitated alerts for adverse trends. Virtual RPM nurses responded to alerts and utilized predefined care pathways. The primary endpoint was the mean proportion of evaluable days spent inpatient (mPEDI) within 30 days of eligibility comparing those who participated in the program (RPM) with those who declined (no RPM). Results: Of 85 eligible patients, 62 were offered DEFeNDR participation. Of those, 34 (54.8%) participated and 28 (45.2%) declined. Baseline characteristics and care utilization outcomes are summarized in Table 1. RPM patients experienced significantly lower mPEDI compared with unmonitored patients [5.1% (Standard Error [SE], 1.9%) vs 12.4% (SE, 2.1%); Wilcoxon Rank Sums p-value, 0.032]. RPM patients also experienced a trend toward fewer total hospital days and lower 30-day readmission rate, as well as shorter mean length of stay and lower rate of ICU utilization when readmitted. Non-visit care activities (EHR clinical communications, documentation, and patient messaging) were decreased from pre-hospital baseline for 58.8% of RPM patients versus 46.6% of those unmonitored. All RPM patients completing a patient satisfaction survey (n=9) indicated that they would recommend the program to patients with a similar condition. Conclusions: Cancer patients with NF participating in the DEFeNDR program experienced a significant reduction in mPEDI and care utilization compared with those who declined. Further studies are warranted to assess comparative effectiveness of this model vs usual care.