Ailawadhi, Sikander

LBA1551 Background: Traditional cancer therapy is primarily delivered in clinical settings, imposing logistical, emotional, and financial burdens, particularly on rural and underserved patients. While international studies have demonstrated the safety of home-based chemotherapy, no randomized U.S. trials have evaluated this approach. Mayo Clinic’s CCBW program aims to expand access to high-quality cancer care by providing in-home cancer treatment, lab testing, telemedicine, remote patient monitoring, command center and paramedic support. This pragmatic randomized controlled trial evaluates feasibility and impact of home-based versus in-clinic cancer directed therapy on patient preference, acceptability, safety, and patient-reported outcomes. Methods: Adult patients (ECOG 0-2) receiving chemotherapy or hormonal therapy at Mayo Clinic Florida were randomized 1:1 after confirmation of treatment tolerance in clinic to receive (1) home-based care for 24 weeks or (2) in-clinic care for 8 weeks followed by home-based care for 16 weeks. Target accrual is 200 patients. A planned interim analysis after 50 enrollments assessed accrual, data completeness, technical challenges, safety, and study outcomes. The primary endpoint is patient ratings of their overall cancer care experience (0–10 scale, CAHPS Cancer Care Survey) at 8 weeks. 200 patients provide 80% power to detect a 0.45 standard deviation difference in mean ratings between arms with a 2-sided 2-sample t-test (α=0.05) and 20% missing data rate. Secondary endpoints are patient preference, comfort with home infusions, treatment worthwhileness, functional/symptom assessments (EORTC QLQ-F17, PRO-CTCAE, GP5), grade ≥3 AEs, hospitalizations, and overall survival. Cost is a tertiary endpoint. The trial is IRB-approved (#23001719) and registered (NCT05969860). Results: Enrollment began 8/23/23. As of 2/21/25, 52 patients (26 per arm) were enrolled and 36 started protocol treatment. Common cancers were breast (38%), colorectal (21%), prostate (19%), and multiple myeloma (14%). 64% (28/44) of patients were female; 84% identified as White, 14% as Black, and 2% as multiple races. Median distance to clinic was 20 miles (range 2-66). After 8 weeks, patients in both arms rated their overall cancer care experience highly (mean [SD]=9.69 [0.85] versus 9.54 [0.66] for home-based vs. in-clinic care, n=26). After 24 weeks, 73% preferred home-based care, 18% had no preference, and 9% preferred in-clinic care; 100% felt comfortable with home infusions. No grade ≥3 AEs related to location of care have occurred. Conclusions: Early findings support the feasibility, safety, and high patient acceptability of home-based cancer therapy. No safety concerns related to care location were observed and most patients preferred home-based treatment. Ongoing accrual and analysis will assess clinical outcomes and cost implications. Clinical trial information: NCT05969860 .

PURPOSE To report the results of the multicenter, open-label IRAKLIA trial (ClinicalTrials.gov identifier: NCT05405166 ) of isatuximab subcutaneous (SC) versus intravenous (IV), plus pomalidomide and dexamethasone, in relapsed/refractory multiple myeloma (MM), to our knowledge, the first phase III MM trial using an on-body injector (OBI). METHODS Patients with ≥1 prior line of therapy were randomly assigned 1:1 to Isa OBI (1,400 mg) or IV (10 mg/kg) once weekly in cycle (C)1 and then every 2 weeks, plus pomalidomide (4 mg once daily, day [D]1-21) and dexamethasone (40 mg once weekly [age ≥75: 20 mg]) and treated until progression, unacceptable toxicity, or patient request. Coprimary end points were overall response rate (ORR; noninferiority margin, 0.839) and Isa C trough (C6D1 predose; noninferiority margin, 0.8). Noninferiority of OBI versus IV was demonstrated if both coprimary end points achieved noninferiority. RESULTS IRAKLIA randomly assigned 531 patients (OBI, n=263; IV, n=268). After 12-month median follow-up, the ORR was 71.1% (OBI) and 70.5% (IV; relative risk, 1.008 [95% CI, 0.903 to 1.126]; lower CI exceeded noninferiority margin). The mean (standard deviation) C6D1 C trough was 499 (259) μg/mL (OBI) and 340 (169) μg/mL (IV). The C trough geometric mean ratio (90% CI) was 1.532 (1.316 to 1.784); lower CI exceeded noninferiority margin. Grade ≥3 treatment-emergent adverse event incidences were 81.7% (OBI) and 76.1% (IV); infusion reaction incidences were 1.5% and 25.0%. Injection site reactions occurred in 0.4% of OBI injections (all grade 1-2); 99.9% of injections completed without interruption. CONCLUSION IRAKLIA demonstrated efficacy and pharmacokinetic noninferiority between Isa OBI and IV. No unexpected safety signal was observed, with excellent local tolerability of Isa OBI. Efficacy and safety were comparable with Isa IV in ICARIA-MM, except the lower OBI infusion reaction rate. These results support potential use of the OBI, designed to improve practice efficiency.

e19503 Background: The uptake of BCMA directed ADCs in MM has been hindered by ocular toxicity. Belantamab mafodotin (BM) and MEDI2228 (MEDI) are BCMA directed monoclonal antibodies conjugated to the microtubule inhibitor, monomethyl auristatin F and the alkylator, pyrrolobenzodiazepine, respectively. Differences in the ADCs payload, antibody specificity and linker stability influence ocular toxicity. We investigated the patterns of ocular toxicity and tolerability of BCMA directed ADC therapy. Methods: Retrospective study of MM patients who commenced treatment with a commercial or investigational BCMA directed ADC at the Mayo Clinic between 2019-22. Results: 111 patients were included, the median age was 69 and median follow up 40 months. The median number of prior treatments was 6, 87% of patients were triple class refractory, 50% penta class refractory, 14% had prior BCMA directed therapy and 24% had extraosseous disease. Treatments included BM (n=56, 50%), BM in combination with other MM therapy (n=12, 11%) and MEDI (n=43, 39%). The overall response rate was 30% for BM and 44% for MEDI. The median OS and PFS for BM was 8 and 2 months, the median OS and PFS for MEDI was 11 and 5 months. The median number of ADC cycles was 2.5. Ocular toxicity is summarized in the table 1. Keratopathy was more common with BM (p=0.004). Only 4 MEDI patients developed keratopathy, all grade 1 and associated with dry eyes and/or photophobia. In contrast, 60% of BM patients developed keratopathy (13% grade 3-4 keratopathy). The median time to keratopathy onset was 1 month with BM, and 2.8 with MEDI. The median time until keratopathy was 4.6 months for BM. Loss of best-corrected visual acuity (VA) was significantly more common with BM (p<0.001). The median time to any decline in VA was 1.5 months for BM and 2.3 for MEDI. The median time until VA returned to baseline was 2.4 months for BM and 2.3 for MEDI. The frequency of dose delays for ocular toxicity was comparable between ADCs, as was the number of dose reductions (16% BM vs. 12% MEDI, p=0.5). The most common reasons for treatment discontinuation were progression or death (BM=69%, MEDI=44%) and ocular toxicity (BM=18%, MEDI=30%). Conclusions: Treatment interruptions, dose reductions and drug discontinuation are common with BCMA directed ADC therapy. Further research to optimize the administration schedule of these agents is warranted. BM and MEDI produce distinct patterns of ocular side effects, namely keratopathy and reduced VA with the former, and photophobia and dry eyes with the latter. BM N = 68 MEDI N = 43 p-value 2 Prophylactic steroid eye drops 4 (6%) 28 (68%) <0.001 Prophylactic lubricant eye drops 42 (63%) 33 (80%) 0.051 Max grade keratopathy 0.004 1-2 29 (47%) 4 (19%) 3-4 8 (13%) 0 (0%) VA equal or worse than 20/40 26 (68%) 6 (20%) <0.001 Days of ADC treatment 59 (33, 167) 68 (41, 105) 0.9 Dose delay for ocular toxicity 19 (28%) 8 (19%) 0.2 n (%); Median (IQR); 2 Chisq test; Wilcoxon rank sum.

e13661 Background: MM survival has improved significantly, resulting in increased survivorship and caregiver burden and is crucial to understand the real-world impact of MM. We analyzed results from a large, prospective MM patient survey using ML models to identify key predictive factors for survivorship and caregiver burden. Methods: A 45-item questionnaire spanning sociodemographics, treatment preferences, symptom burden and caregiver impact was distributed to MM patients at Mayo Clinic and International Myeloma Foundation support groups. Questions about quality of life (QOL) and treatment satisfaction (TS) represented survivorship outcomes while caregiver workday loss (WL) and job loss (JL) were surrogates for caregiver burden. 6 ML models (multinomial, random forest (RF), XGB (XGBoost), k-NN, GBM, Naïve Bayes) with a training: testing cohort of 80:20 were used to predict each of the 4 outcomes independently, considering model accuracy, C-index, precision, recall, and F1 score (Table), and using R studio (V4.4.1) and Bluesky Statistics (V10.3.4). Results: 2,239 participants (54% male, 89% Whites) with median age 68 yrs completed the survey. 71% respondents had a college degree, 44% resided in Midwest states, 62% reported household income >$75,000, and 67% had Medicare/Medicaid. Median age at MM diagnosis was 67 yrs with 58% diagnosed within the past 5 yrs and 73% currently receiving MM treatment. 72% reported their spouse as the primary caregiver. XGB was the best predictive model for QOL with gender, household income, stem cell transplant, CAR-T therapy, support from medical staff, and symptom burden (pain, neuropathy, mental well-being) as significant predictors. The RF model was the best for TS with pain and neuropathy levels as the most impactful predictors. For caregiver burden, XGB was the best model for WL with gender, household income, CAR-T therapy, financial strain, lack of support from medical staff, self-workdays missed, self-job loss, and pain and neuropathy levels as significant predictors. For JL, RF was the best model with significant variables being workdays missed by self, increased healthcare needs, symptom burden (pain, neuropathy, and mental well-being), and restricted physical activity. Conclusions: Our study shows the significant impact of MM survivorship and efficiently identifies predictive factors associated with survivorship and caregiver burden from a large prospective dataset using validated ML models. These findings highlight the complex challenges from MM and provide contemporary ML methods to better understand their interplay such that a framework of real-world interventions can be developed. Outcome Best ML Model Accuracy C-Index Precision Recall F1 score QOL XG 0.996 0.996 0.996 0.997 0.996 TS RF 0.984 0.900 0.937 0.948 0.937 WL XGB 0.984 1.000 0.944 0.947 0.945 JL RF 0.989 0.800 0.829 0.848 0.835

7522 Background: Movement and neurocognitive treatment emergent adverse events (MNTs), cranial nerve palsies (CNPs) and immune-effector cell enterocolitis (IEC-EC) are late onset toxicities associated with cilta-cel and are associated with significant morbidity and mortality. We aimed to identify predisposing risk factors to allow for formulating risk-reduction strategies. Methods: Retrospective study of MM pts who received FDA approved cilta-cel at Mayo Clinic between Feb 2022-Dec 2024. Interrogated factors included demographics, disease and treatment characteristics, and selected lab values at different time points. In odds ratio (OR) analyses, pts were divided by toxicity type (1) No delayed toxicity (2) MNT (3) IEC-EC without MNT (4) isolated CNP. Differences between pts in the MNT, IEC-EC and CNP groups were compared separately in a pairwise manner vs. those with no delayed toxicity. Results: Of 235 pts, 26 (11%) had delayed toxicity [MNT = 8 (3%), IEC-EC = 9 (4%), CNP = 14 (6%)]; 3 pts had both MNT/IEC-EC and 2 had both CNP/IEC-EC. Median onset from CAR-T infusion for MNT, IEC-EC and CNP was 19 (range 8-96), 106 (35-169) and 21 (7-43) days respectively. Of 164 evaluable pts, those who had ICANS had increased odds for any delayed toxicity (OR 4.7; 95% CI 1.6-13.8). Pts who had ICANS (OR 7.7; 1.6-36.9), HLH/MAS (OR 6.2; 1.1-6.7) and Ferritin >400mcg/L at time of lymphodepletion (OR 6.3; 1.5-32) had increased odds for MNTs. Pts who received alkylator-based bridging therapy had increased odds (OR 6.1; 1.1-35) for IEC-EC. Analysis of serial post-CAR infusion lab values showed that peak ALC was the most significant variable with differences between groups shown in table. Median time to peak ALC was 12 days (IQR 11-13). ROC analysis determined peak ALC >3 x 10 9 /L as a meaningful cut point. Pts with peak ALC >3.0 x 10 9 /L had increased odds of developing any delayed toxicity (OR 9.3; 3.5-29.3), MNT and CNP (table). Absolute risk of any delayed toxicity was 33% in pts with peak ALC >3 x 10 9 /L vs 5% without. At this threshold, number needed to treat was 3.6. Conclusions: Real-world data shows that cilta-cel associated delayed toxicity is seen in ~10% of patients, with specific toxicity rates between 4-8%. Factors associated with these toxicities predominantly occur in the post CAR-T infusion period. Given that ALC expansion in the first 2 weeks correlate with CAR-T expansion, peak ALC is potentially predictive of toxicity and 3 x 10 9 /L may be an interventional threshold for primary prophylaxis. Peak ALC by toxicity groups. No ToxN=138 MNTN=8 CNPN=12 IEC-ECN=6 p value Peak ALC (10 9 /L), median (IQR) 1.8 (1.0-4.1) 6.2 (4.8-14.4) 4.3 (3.2-6.7) 3.6 (1.9-5.2) <0.001 1 ALC >3 x 10 9 /L, n (%) 43 (31%) 7 (88%) 10 (83%) 4 (67%) <0.001 2 Odd Ratios vs no Tox 3 , 95% CI 15.5 (2.6-293.7) 11.0 (2.8-73.9) 4.4 (0.8-25.0) 1 Wilcoxon/Kruskal-Wallis Tests, 2 Chi square test, 3 Logistic regression analysis.

7506 Background: IV Isa-Pd is approved to treat RRMM patients (pts) based on the ICARIA-MM study. A Phase 1b study showed safety and efficacy of Isa SC via an OBDS, an investigational wearable bolus injector, plus Pd, in RRMM pts. Isa SC offers shorter duration, fixed dose and smaller administration volume. Here, we report results of the IRAKLIA trial (NCT05405166); Isa SC vs IV + Pd in RRMM pts, the first Phase 3 myeloma trial reporting the use of an OBDS. Methods: This multicenter, open-label study enrolled pts aged ≥18 years with ≥1 prior line of therapy (LOT). Pts were randomized 1:1 to Isa SC (1400 mg) or Isa IV (10 mg/kg) weekly in Cycle (C)1, then every 2 weeks + P (4 mg/day, Day [D]1–21) + d (40 mg [20 mg if age ≥75 years] weekly). Pts had 4-week cycles until progression, unacceptable toxicity or patient request. Co-primary endpoints were overall response rate (ORR; non-inferiority [NI] margin of 0.839) and Isa trough level (C trough ) at steady state (predose at C6D1; NI if lower limit of 90% CI of geometric mean ratio ≥0.8). Results: 531 pts (SC n=263; IV n=268 [4 not treated]) were randomized. Baseline characteristics were balanced (median age 66 years; median 2 prior LOT). After median 12 months follow-up, ORR was 71% (SC arm) and 71% (IV arm; relative risk [95% CI] = 1.008 [0.903–1.126]; lower CI > NI margin). Mean (SD) C trough at C6D1 was 499 (259) μg/mL for SC and 340 (169) μg/mL for IV. C trough geometric mean ratio (90% CI) was 1.532 (1.316–1.784); lower CI > NI margin. Co-primary and all 4 key secondary endpoints including pt experience are in the Table. Grade ≥3 treatment-emergent adverse events occurred in 82% (SC) and 76% (IV) of pts; with treatment discontinuation rates of 8% and 9%. Injection site reactions (ISRs) occurred in 4% (11/263) of the SC arm and in 19 (0.4%) of 5145 SC injections (all Grade 1–2). 99.9% of OBDS injections were completed without interruption. Conclusions: IRAKLIA met its co-primary endpoints, showing efficacy and pharmacokinetic NI between Isa SC vs IV + Pd. No new safety signal besides a low ISR incidence was observed, showing excellent Isa SC tolerability. Far fewer infusion reactions and higher pt satisfaction were also noted for SC vs IV. Efficacy and safety are comparable to Isa IV in ICARIA-MM. These results support potential use of Isa SC delivered via the OBDS, designed to improve pt experience and practice efficiency. Clinical trial information: NCT05405166 . Isa SC + Pd Isa IV + Pd Efficacy, % N=263 N=268 ORR 71 71 ≥VGPR 46 46 PK*, µg/mL N=131/121 N=126/121 Geometric mean Isa C trough at C2D1 / C6D1 360/426 277/278 Safety, % N=263 N=264 All grade IR 2 25 Pt satisfaction with injection method at C5D15, % 70 53 *PK was analyzed at C6D1 with PP PK population and at C2D1 with PP CT4W population. CT4W, C trough at 4 weeks; IR, infusion reaction; PK, pharmacokinetics; PP, per protocol; VGPR, very good partial response.

e19033 Background: CLL tends to affect older individuals, and older patients often endure greater health disparities and treatment burdens that may impact their access to healthcare resources, adherence to treatment regimens and treatment outcomes (UN, Health Inequalities in Old Age). This study aimed to assess treatment utilization patterns, discontinuation, and healthcare resource utilization (HCRU) of 1L use of BTKi in CLL, focusing on older patients ≥65 years (yrs). Methods: A retrospective observational study using the Symphony Integrated Dataverse was conducted to identify adult CLL patients initiating a 1L BTKi (zanubrutinib [ZANU], acalabrutinib [ACA] or ibrutinib [IBR]) treatment regimen from 02/2022 and 09/2024 (index period). Patients were required to have ≥30 days of continuous enrollment in the pre- and post-index periods. Patients initiating a BTKi were further categorized by age at index date. Patient sociodemographic, clinical characteristics, and outcomes were reported in overall and older (≥65 yrs) CLL patients by each BTKi group. Treatment discontinuation rate was examined at 60, 90, 120, 150, 180, and 360 days, and by median time to discontinuation (TTD), estimated using the Kaplan-Meier method, censoring patients at the end of follow-up. HCRU (outpatient, inpatient, and other services) was evaluated during time on treatment and over the follow-up period and reported as per-patient-per-year (PPPY). Results: A total of 6,846 patients initiated a 1L BTKi (ZANU: n=1,853; ACA: 3,519; IBR: 1,474) for CLL during the index period. Patients receiving ZANU were older (mean age: 70.9 yrs; 78% ≥65 yrs) than those receiving ACA (69.4 yrs; 71% ≥65 yrs) and IBR (69.6 yrs; 73% ≥65 yrs). Payer type and geography were significantly different across each BTKi group ( p <.001). There were no significant differences across the BTKis regarding baseline comorbidities. ZANU patients had the longest estimated median TTD overall (ZANU: 18.9 months [m], ACA: 17.8 m, IBR: 14.5 m; p <.001) and in patients ≥65 yrs (ZANU: 17.2 m, ACA: 15.2 m, IBR: 12.6 m; p <.001). ZANU patients also had the lowest estimated discontinuation rates at 60- , 90-, 120-, 150-, 180-, and 360-days post BTKi initiation in the overall and ≥65 yrs groups. There were significant differences across the BTKi group for inpatient visits PPPY in all patients and ≥65 yrs with ZANU having the lowest visits of the BTKis (ZANU: 2.6, ACA: 3.6, IBR: 4.6; p =.029 and ZANU: 2.5, ACA: 4.3, IBR: 5.3; p =.004, respectively). Conclusions: This real-world study demonstrated that CLL patients treated with ZANU had longer TTD, lower discontinuation rates, and less HCRU than ACA and IBR across all patients and specifically in older patients ≥65 yrs. Further studies on long-term and clinical outcomes are warranted.