Remote Patient Monitoring for Early Detection of Cytokine Release Syndrome in Myeloma Patients: A Comparative Study between Standard Care and Remote Monitoring

Introduction:

Bispecific antibodies (bsAb) against BCMA, GPRC5D and FcRH5 have shown to be highly active in relapsed and refractory multiple myeloma (RRMM). Initial bsAb use can be complicated by cytokine release syndrome (CRS). Fever is a cardinal symptom of all CRS grades and step-up dosing a mitigation strategy to prevent severe CRS. Step-up dosing requires on average 7-10 days of patient monitoring, a period during which many patients are currently still hospitalized. With the advancements in wearable technology, remote patient monitoring (RPM) offers a promising approach for early CRS detection. Although this could enable ambulatory patient care and improve healthcare efficiency, the benefit of RPM should be validated prospectively in comparison with standard patient care.

Aim of the study:

Our study has explored the effectiveness of RPM in comparison with standard of care (SoC) monitoring to detect early CRS in patients with RRMM receiving a bsAb. Secondary endpoints were patient acceptability and usability of the RPM devices.

Material and Methods:

This monocentric academic study included patients with RRMM treated with a bsAb (teclistamab, talquetamab, cevostamab). All patients were hospitalized and received SoC in addition to RPM monitoring. Vital signs: temperature, heart rate (HR), respiratory rate (RR), heart rate variability (HRV) were monitored every 5 minutes using the Byteflies® RPM platform combining an adhesive axillary thermometer (SteadyTemp®) and an ECG patch. In parallel, a nurse assessed temperature, blood pressure, HR, RR, and oxygen saturation every six hours or on patients request without access to RPM data. Early warning for CRS was defined as the first fever episode (T>38°C) after bsAb administration measured by SoC. Trends in parameters 2 hours before CRS were analyzed post hoc. Patient acceptance and RPM usability were evaluated by questionnaires and interviews.

Results:

At the time of this interim analysis, 14 patients (4 men: 29%; 10 women: 71%) with a median age of 71 y (range: 57-76) were enrolled. BsAb administered were: teclistamab: 57%, talquetamab: 36%, Cevostamab: 7%. Median hospitalization duration was 10 days (range: 5-18). Overall, CRS was observed in 57% of patients (grade 1: 43%; grade 2: 14%, grade ≥ 3: 0%), with 29% experiencing 2 CRS episodes. The highest CRS occurrence (58%) was after the second step-up dose.

A total of 44 bsAb administrations were evaluated of which 12 were positive for CRS. All CRS episodes detected by SoC were identified significantly earlier by RPM. SteadyTemp® detected fever on average 4 hours and 45 min earlier than SoC (SD ± 2 h and 47 min). Moreover, SteadyTemp® detected fever after 6 bsAb administrations involving 4 patients, while SoC did not detect a temperature increase > 38°C. In addition, RPM detected significant differences between baseline and pre-CRS event for: temperature (1.7°C increase, p<0.0001), HR (16.66 bpm increase, p=0.0001) and RR (1.86 breaths/min increase, p=0.0240) up to 2 hours before CRS grade 1 detection by SoC. No significant HRV differences were observed. Finally, patient feedback indicated high acceptability and satisfaction with the RPM program. Patients reported confidence, ease of use, and preference for RPM over hospital stays, with average scores above 6 on a 7-point scale.

Conclusion:

This RPM solution showed increased sensitivity and a significant shorter lead time to detect CRS after bsAb administration compared to SoC. More specifically, we were able to detect fever nearly 5 hours earlier with the RPM and therefore to detect CRS grade 1 and 2 largely in advance of Soc. Patients found the RPM system acceptable and user-friendly, and expressed a strong preference for home monitoring. These findings offer opportunities for safe and controlled RPM use in an outpatient setting after bsAb administration. In addition, our observations endorse further investigation into the RPM system, particularly on the added value of more comprehensive measurements to the temperature only assessment for early CRS detection.

Acknowledgement:

this work was supported by a grant from Flanders Innovation and Entrepreneurship (VLAIO)