A Pragmatic Approach for Quantifying Treatment Tolerability in Multiple Myeloma Clinical Practice Using Patient-Reported Outcomes (PROs)

Background Cancer care has moved beyond treatment response and survival to include the patient experience, that is, how the patient feels and functions during treatment. Treatment tolerability is no longer assessed only by the clinician, but also incorporates patient's voices1-3. Patients with multiple myeloma (MM) are often on a lengthy course of therapy, emphasizing the importance of maintaining quality-of-life (QoL). Patient-reported outcomes (PROs) collected through remote symptom monitoring can bolster understanding of tolerability from the patients' perspectives. A recent publication by Brose et al. (2024) quantified patient-reported tolerability (PRT) in thyroid cancer4. This study aimed to adopt this novel methodology to explore PRT in patients with MM using PROs collected in real-world clinical practice. Methods Study participants were enrolled in Carevive PROmpt®, a remote symptom monitoring (RSM) platform, and received MM treatment between 9/2020 and 6/2024. Patients completed at least one weekly PRO survey that included treatment bother, measured by a single item FACT-GP5 (“I am bothered by side effects of treatment”), and were followed from baseline survey completion until last survey completion or end of study period (whichever was earliest). Treatment data (name, start, and end dates) were sourced from the electronic medical record or entered directly into the PROmpt® platform by the care team. Treatment tolerability (TT) was defined as the degree of treatment bother and was classified into two categories: 1) high treatment bother (HTB), defined as response 3 (“Quite a bit”) or 4 (“Very much”) and 2) low treatment bother (LTB), defined as response 0 (“Not at all”), 1 (“A little bit”), or 2 (“Somewhat”) to the single item FACT-GP5 on a given survey. PRT was calculated as the proportion of time on treatment with high treatment bother (1-25%, 26-50%, 51-75%, and 76-100%). Persistent HTB was defined as reporting HTB 76-100% of the time. Results were analyzed by therapeutic intent (Induction/Consolidation, Maintenance), PRO assessment time (week 1-4 vs. week 5+), and baseline frailty status (Fit or Intermediate/Frail). Results A total of 181 patients were included in the study, of which 61 (33.7%) reported the treatment bother to be “Quite a bit” or “Very much” at least once. Patients in the study cohort had a median age of 65, with 50% males, 73% White, 22% Black, 25% first-line, and a median follow-up of 11.7 weeks. The distribution of therapeutic intent was 55% Maintenance, 28% Induction/Consolidation, 1% Transplant, and 16% not specified. Most patients (82%) experienced HTB up to 25% of the time, 6.6% experienced HTB 26-50% of the time, 4.4% experienced HTB 51-75% of the time, and 7.1% experienced persistent HTB (76-100% of the time). Incidence rate of HTB was 3.46 per 100 patients per week. Persistent HTB was highest in line 4 or later (11.3%) and was higher during Maintenance (8.8%) than Induction/Consolidation (5.1%). Persistent HTB appeared comparable between Fit and Intermediate/Frail groups (7% vs. 7.6%, respectively). When examined by PRO assessment time, the proportion of patients with persistent HTB in the Metastatic settings decreased from week 1-4 (11.4%) to week 5 or later (7.7%), while the proportion appeared to be consistent in the Induction/Consolidation group (5.3% vs. 5.7%, respectively). Conclusions This study used PROs to quantify treatment tolerability in patients receiving MM therapy in real-world clinical practice. Overall, 7.1% of patients reported persistent HTB. HTB was highest in the later line (4L+) and Maintenance settings. Persistent HTB was similar by baseline frailty. Despite some directional decline beyond week 1-4, notable persistent HTB remained in patients on Maintenance therapy. This methodology incorporated patients' voices to quantify longitudinal tolerability and, in this study, highlighted a need for more tolerable MM treatments particularly in the Maintenance settings. Future studies should focus on factors that impact tolerability, symptom persistence, and impact of treatment bother on QoL and healthcare resource utilization.