Electronic Patient-Reported Outcome (ePRO) Symptom Monitoring for Relapsed/Refractory Multiple Myeloma in Community Settings, Focusing on Bispecific Antibody Therapy

Introduction: Patient monitoring with electronic patient-reported outcomes (ePROs) has been shown to improve patient quality of life, increase time on treatment, and reduce hospital utilization in both clinical trial and real-world settings for solid tumors but there is a paucity of evidence for patients with hematologic malignancies. Moreover, with the introduction of highly effective but potentially toxic therapies such as bispecific antibodies (BsAbs) for relapsed/refractory multiple myeloma (RRMM), it is unknown if ePROs can identify important early toxicities such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), or late toxicities such as infection in a timely manner. We investigated the ability of ePROs to identify key symptoms during treatment of RRMM compared to by telephone alone, including those receiving BsAbs for MM and other hematologic malignancies.

Methods: Patients in community-based practices were invited to use the Canopy ePRO system prior to therapy. The Canopy ePRO system is a proprietary, cloud-based system that integrates with electronic medical records to enable patient-practice communication. Patients can submit scheduled or unscheduled reports of their symptoms using smart devices or an interactive telephone-based system. Clinicians have access to a queue of ePRO reports, prioritized by severity, and are provided with standardized triage pathways for evaluation by telephone to determine if an unscheduled visit is necessary. Tests of difference were adjusted for multiple comparisons using the Hochberg method.

For patients receiving triplet therapies for RRMM or BsAbs for hematologic malignancies, we evaluated symptoms submitted by ePRO compared with patient-reported symptoms by telephone across 6 large community practices from July 2020 through June 2024.

Results: There were 393 patients identified who received triplet therapies for RRMM. The most common regimens received were an anti-CD38 monoclonal antibody with either pomalidomide/dex (Pd) or carfilzomib/dex (Kd) (n=23 and n=24, respectively), and KPd (n=13). 66 patients submitted at least one ePRO report and 69 of 327 patients without ePRO access reported symptoms by calling into the office.

At 30 days after treatment, 45% of patients in the ePRO cohort had submitted an ePRO report (95% CI: 0.345, 0.557) versus 12.9% of patients in the phone cohort calling in a symptom (95% CI: 0.087, 0.180). With respect to specific symptoms, patients enrolled in ePROs reported a higher frequency of every symptom compared to those not enrolled, including symptoms necessitating clinical attention: fever (4.5% ePRO vs 1.5% phone, p=1.0), fatigue (23% vs 1%, p=<0.001), pain (23% vs 2%, p=0.019), headache (6% vs 0.3%, p=0.065), breathing difficulty (11% vs 0.6%, p=0.001), cough (6% vs 1.5%, p=0.533), memory issues (9% vs 0%, p<0.001), and falls or balance issues (4.5% vs 0.3%, p=0.297). Patients reporting symptoms by ePROs had a higher frequency of non-treatment MD visits in the three days following symptom reports compared to those reporting by phone (35% vs 8%, p<0.001).

Separately from the RRMM cohort, 83 patients received a BsAb for a hematologic malignancy (35 with MM, including 5 with outpatient step-up dosing). 46 (55%) patients were offered the chance to enroll in the ePROs program, and 18 (22%) submitted at least one ePRO report during treatment (n = 9 with MM).

We observed similar patterns in symptom reporting to the RRMM cohort, patients receiving BsAbs who submitted ePROs reported symptoms at a higher frequency compared to those who were not enrolled, including symptoms necessitating clinical attention: fever (11% vs 9.2%, p=1.0), fatigue (55.6% vs 1.5%, p<0.001), pain (38.9% vs 9.2%, p=0.060), headache (33.3% vs 0%), breathing difficulty (11% vs 3.1%, p=1.0), cough (16.7% vs 4.8, p=1.0), lightheadedness (22.2% vs 1.2%, p=0.077), and memory issues (22.2% vs 0%).

Conclusions: Patients with RRMM who enroll in ePROs are much more likely to report symptoms remotely, likely as a result fewer barriers to symptom reporting and prompting to report by ePRO. Nearly all symptoms are reported more frequently by ePRO than phone, including important symptoms unique to BsABs. Some symptoms that are detected by ePRO are clinically actionable, and communicating those symptoms to clinics might improve patient care. ePROs may better facilitate outpatient administration of BsAbs.