OBJECTIVES/GOALS: Patients with multiple myeloma (MM) experience significant disease- and treatment-related symptom burden, especially with higher lines of therapy (LOT). We used a remote symptom monitoring app to characterize overall symptom profile, symptom bother, and quality of life (QOL) among patients with MM across LOT and longitudinally. METHODS/STUDY POPULATION: We used Carevive PROmpt, a symptom monitoring app for cancer patients. From 11/10/22 to 9/27/23, we enrolled 84 adult patients with MM of any stage and anywhere in the treatment continuum from Duke Health MM clinics. Participants received weekly symptom surveys while on active treatment. Per prior studies, we defined heavily pretreated patients as those on current LOT ≥4. Our sample had a mean (SD) age of 63.7 (10.8) years and was 56.0% male; 73.8% had a prior bone marrow transplant, 40.5% were on LOT ≥4 (53.6% on LOT <4, 6.0% missing), 58.3% were on triplet therapy or higher. For 14 symptoms, we described the prevalence of moderate to very severe (MOD-VS) symptoms based on LOT overall and over time. We also described responses to “How bothersome are treatment side effects?” and “Overall QOL over the past week” based on LOT. RESULTS/ANTICIPATED RESULTS: Surveys continued for a mean (SD) of 14.9 (9.6) weeks (range: 44). The top 5 MOD-VS symptoms ever experienced were fatigue (66.7% of patients), neuropathy (48.8%), muscle pain (44.0%), insomnia (39.3%), and general pain (38.1%). Patients on LOT ≥4 had most of these symptoms more often than LOT <4 (fatigue: 70.6% of patients vs. 60.0%, neuropathy: 71.8% vs. 40.0%, muscle pain: 47.1% vs. 42.2%, insomnia: 35.3% vs. 40.0%, general pain: 47.1% vs. 33.3%). For those on LOT ≥4, 42.9% of survey responses endorsed “somewhat”, “quite a bit”, or “very much” symptom bother compared to 32.7% for LOT <4. QOL was similar between groups. Over many months, patients on LOT ≥4 had several persistent symptoms (neuropathy, sadness, insomnia), but even those on LOT <4 had unmet symptom needs (fatigue, general pain, constipation). DISCUSSION/SIGNIFICANCE: Evidence shows that treatment selection at higher LOT in MM often underrates the impact of cumulative symptom burden. Our study reveals significant longitudinal unmet needs regarding symptom and distress management in MM; understanding this can help guide treatment decisions and palliative care for MM patients with escalating treatment demands.