7568 Background: BVd is approved in the United States as a third-line or later (3L+) option for patients with RRMM based on the DREAMM-7 study of BVd vs daratumumab (D) plus bortezomib (V) and dexamethasone (d; DVd). This study aimed to compare the relative efficacy of BVd vs pomalidomide (P) plus Vd (PVd), elotuzumab plus Pd (EPd), isatuximab plus Pd (IsaPd), and idecabtagene vicleucel (ide-cel) in adults with 3L+ RRMM who received a proteasome inhibitor and an immunomodulatory drug. In the absence of head-to-head trials, indirect treatment comparisons (ITCs) can inform on the relative efficacy of regimens. Methods: ITCs of progression-free survival (PFS) and overall survival (OS) were conducted using the eligible study populations (only patients with ≥2 prior lines of therapy [LOT]) from the DREAMM-7 (BVd), DREAMM-8 (PVd), ELOQUENT-3 (EPd), ICARIA-MM (IsaPd), and KarMMA-3 (ide-cel) trials. Individual pt data (IPD) were available for patients treated with BVd and PVd, while only published summary data were available for patients treated with EPd, IsaPd, and ide-cel. In base-case analyses, study populations were weighted (using inverse probability of treatment weighting to compare to PVd and matching adjusted indirect comparison for the other treatments) to match in terms of age, prior exposure to bortezomib, prior exposure to lenalidomide, refractoriness to lenalidomide, number of prior LOT, and cytogenetic risk. Weighting was done separately for each comparator treatment. Weighted Cox regression was then performed to compare outcomes of patients treated with BVd to each respective comparator treatment. Results: In the base-case models, weighting yielded very good balance for all matched covariates (standardized mean difference <0.25 for each covariate across each comparison, and <0.10 in all cases except for age, prior bortezomib, and >4 prior LOT in the PVd comparison). Hazard ratios for BVd vs EPd, IsaPd, and ide-cel for PFS and OS significantly favored BVd (Table). For BVd vs PVd, PFS significantly favored BVd and OS numerically favored BVd. Conclusions: In DREAMM-7, direct comparison of BVd vs DVd showed PFS and OS improvements with BVd. This indirect comparison of patients in the 3L+ setting further showed that BVd improved PFS and OS vs PVd, EPd, IsaPd, and ide-cel. Comparison (sample size/effective sample size value) BVd vs PVd (86 and 68/35) BVd vs EPd(103/42 and 60) BVd vs IsaPd(85/52 and 154) BVd vs Ide-cel(96/50 and 254) Outcome PFS OS PFS OS PFS OS PFS OS Hazard ratio 0.517 0.604 0.337 0.405 0.538 0.348 0.468 0.509 95% confidence interval 0.275, 0.972 0.331, 1.103 0.173, 0.654 0.209, 0.787 0.346, 0.836 0.195, 0.623 0.287, 0.762 0.274, 0.945 p-value 0.041 0.101 0.001 0.008 0.006 <0.001 0.002 0.033

7530 Background: B-cell maturation antigen (BCMA)-directed CAR-T therapy is a highly effective treatment with potential for long-term remission of RRMM with improved outcomes vs daratumumab-based regimens. CAR-T suitability may be limited by delays/manufacturing failure and changes in pt condition, financial situation, or access to specialized treatment centers. We characterized pts with RRMM who underwent leukapheresis to prepare for CAR-T and pt treatment waiting time, to understand the delays incurred prior to CAR-T infusion. Methods: A real-world study in the US using the PharMetrics Plus claims database (July 2020–September 2024) was performed. Eligible pts were aged ≥18 years with RRMM, had their first leukapheresis claim (index date) during the index period (March 2021–August 2024), were continuously enrolled in medical/pharmacy benefits for ≥180 days prior to and ≥30 days after index date, and were not clinical trial participants. Pt characteristics, rate of CAR-T receipt, and time to CAR-T receipt were assessed during the variable follow-up. Results: Overall, 337 pts who received leukapheresis were identified. Median (interquartile range) age was 62 (55–67) years, and 59.1% of pts were male. Mean National Cancer Institute (NCI) comorbidity index was 0.52. Most pts received care in the Midwest (31.8%) or Northeast (24.6%) regions. Most pts (95.9%) received leukapheresis in an outpatient setting. Median available follow-up time was 255 days (mean 337 days). During follow-up, 183 pts (54.3%) did not receive CAR-T after leukapheresis. Among pts who had ≥12 months of follow-up (n=143), the proportion of pts who did not receive CAR-T was similar at 53.1% (n=76). Among pts who received CAR-T during the follow-up (n=154; 45.7%), the median waiting time was 54.0 days (mean 56.7 days). The cohort of pts who did not receive CAR-T had a higher proportion of females (48.6%/31.8%), were more likely to have Medicaid (29.5%/7.8%), had higher NCI comorbidity index (scores 0.55/0.47), and most commonly received care in the Northeast (35.5%/11.7%) while pts who received CAR-T most commonly received care in the Midwest (23.0%/42.2%). The most common first classes of multiple myeloma medications after leukapheresis but prior to CAR-T infusion in pts who did/did not receive CAR-T were an alkylating agent (65.6%/36.1%), proteasome inhibitor (40.3%/30.6%), steroid (38.3%/39.3%), immunomodulatory drug (22.7%/27.3%), anti-CD38 (20.8%/20.8%), and stem cell transplant (0%/17.5%). Conclusions: Over half of pts receiving leukapheresis did not receive CAR-T infusion, highlighting a persistent gap between eligibility and treatment delivery. These data emphasize an urgent need for broadly accessible BCMA-targeted therapies that provide deep and durable responses.

Introduction:The phase III DREAMM-8 study (NCT04484623) evaluated belantamab mafodotin, an antibody-drug conjugate targeting B-cell maturation antigen, plus pomalidomide (P) + dexamethasone (d; BPd) vs P + bortezomib (V) + d (PVd) in lenalidomide (len)-exposed patients with relapsed/refractory multiple myeloma (RRMM) who had ≥1 prior line of therapy (2L+). Improved progression-free survival (PFS; primary endpoint) was observed with BPd vs PVd (median PFS not reached for BPd vs 12.7 months for PVd; hazard ratio [HR] 0.52 [95% confidence interval: 0.37, 0.73], P<0.001). In the absence of head-to-head trials, an indirect treatment comparison (ITC) was used to compare PFS with BPd vs other regimens of interest for patients with len-exposed 2L+ RRMM. Methods: A systematic literature review identified randomized controlled trials (RCTs) (Jan 2008–Jan 2024) that reported PFS with regimens used in adults with 2L+ RRMM who had disease progression on/after their most recent therapy. Only RCTs that evaluated a regimen approved by the US Food and Drug Administration/European Medicines Agency, or which were of interest for health technology assessment, were included. In the len-exposed population, trials were linked by the treatment(s) they shared to form connected evidence networks (trials not part of the networks were excluded), and a fixed effects network meta-analysis (NMA) was conducted to compare PFS across RCTs. To validate the network structure, scenario analysis using an inverse probability of treatment weighting (IPTW) was performed that compared outcomes for patients receiving BPd (DREAMM-8) vs daratumumab (D) + Vd (DVd; DREAMM-7) and included in the network. Hazard ratios <1 indicated BPd was more effective than the comparator regimen, and 95% credible intervals (CrIs) that did not cross 1 indicated high probability that the treatment effect favored BPd. Deviance information criteria were used to estimate statistical fit for each model. Results: In the len-exposed population, the PFS network comprised 8 RCTs (including DREAMM-8) with comparator regimens: carfilzomib + dexamethasone (Kd), Kd + daratumumab (DKd), isatuximab + carfilzomib + dexamethasone (IsaKd), bortezomib + dexamethasone (Vd), DVd, PVd, and selinexor + Vd (SVd). The NMA found that BPd provided the longest PFS vs all included comparators (HR 0.29–0.86). Comparisons vs Vd (HR [CrI] 0.29 [0.20, 0.43]), high-dose (h)Kd (0.42 [0.26, 0.69]), SVd (0.46 [0.26, 0.83]), and PVd (0.52 [0.37, 0.73]) had 95% CrIs that did not cross 1. Comparisons vs Kd (HR [CrI] 0.58 [0.34, 1.01]), DKd (0.86 [0.46, 1.62]), IsaKd (0.73 [0.36, 1.47]), and DVd (0.73 [0.43, 1.25]) had 95% CrIs that crossed 1, but the trend favored BPd. The IPTW analysis using patient-level data showed BPd (DREAMM-8) provided longer PFS than DVd (DREAMM-7) (HR [CrI] 0.41 [0.25, 0.65]). When including results of the IPTW analysis of BPd vs DVd in the network in place of DREAMM-8 BPd vs PVd, BPd continued to provide the longest PFS vs all included comparators (HR 0.16–0.48), with 95% CrIs remaining below 1 for all comparisons except for BPd vs DKd (HR [CrI] 0.48 [0.22, 1.04]), indicating high probability of the treatment effect favoring BPd for these comparisons. Conclusions: In the absence of head-to-head randomized controlled trials, these ITC data suggested a high probability that PFS consistently favored BPd vs comparator regimens of interest in len-exposed patients with RRMM, with consistent findings in the IPTW analysis reducing uncertainty in the base-case NMA findings.

Introduction: Chimeric antigen receptor T-cell(CAR-T) therapies targeting B-cell maturation antigen are now established in the treatment landscape for multiple myeloma (MM); however, clinical decision-making may be influenced by real-world logistical and healthcare resource utilization (HCRU) considerations alongside treatment efficacy. A clearer understanding of HCRU with CAR-T therapies in MM is needed. Here we report the real-world demographics, administration-related HCRU, and post-administration HCRU of patients who received idecabtagene vicleucel (ide-cel) or ciltacabtagene autoleucel (cilta-cel). Methods: This retrospective cohort study used IQVIA PharMetrics Plus® Enhanced Closed Claims database. Included patients were adults with MM who were not participating in clinical trials and who had the first claim for ide-cel/cilta-cel within the relevant FDA-approved period (from Mar 1, 2021 for ide-cel and Feb 1, 2022 for cilta-cel). Continuous enrollment in medical and pharmacy benefits for ≥6 months before and ≥1 month after the first record of CAR-T administration (index date) was required. Patient demographics were evaluated in the 6 months prior to or on the index date. Administration-related HCRU was evaluated on the index date, and post-administration HCRU was evaluated in the 30 days following the index date. The study periods were from Sep 1, 2020 (ide-cel)/Aug 1, 2021 (cilta-cel) until Sep 30, 2024. Results: The ide-cel cohort included 89 patients and the cilta-cel cohort included 144 patients. Median (interquartile range) ages were 65 (59–70) years for ide-cel and 62 (57–68) years for cilta-cel, and most patients were male (62.9% ide-cel/67.4% cilta-cel). Both CAR-T therapies were most commonly administered in inpatient settings (83.1% ide-cel/52.8% cilta-cel), and most patients receiving each agent had an inpatient admission on the index date (92.1% ide-cel/58.3% cilta-cel). Mean (standard deviation [SD]) lengths of inpatient admission at index were 15.9 (13.3)/18.9 (19.6) days for ide-cel/cilta-cel. Intensive care unit (ICU) visits on index date were reported for 33.7%/20.1% of patients receiving ide-cel/cilta-cel, with a mean (SD) length of stay of 12.5 (13.4)/13.7 (7.7) days. In the 30 days post-administration, 7.9%/34.7% of patients receiving ide-cel/cilta-cel had ≥1 all-cause inpatient admission, with 4.5%/16.0% having an ICU stay, and 3.4%/10.4% having an emergency room (ER) visit. Patients treated with ide-cel/cilta-cel had mean (SD) inpatient stays of 9.7 (6.3)/6.9 (4.4) days and ICU stays of 8.8 (7.2)/7.2 (4.8) days. The most common diagnoses observed in the 30 days post ide-cel/cilta-cel administration were hematologic complications (65.2%/60.4%; including neutropenia, anemia, thrombocytopenia, and leukopenia), cytokine release syndrome (CRS: 60.7%/56.3%), and hypertension (49.4%/34.0%). Inpatient admissions related to hematologic complications/CRS/hypertension occurred in 47.2%/57.3%/43.8% of patients receiving ide-cel and 41.0%/53.5%/24.3% of patients receiving cilta-cel. Infections in the 30 days post ide-cel/cilta-cel administration occurred in 4.5%/8.3% of patients. Patients receiving ide-cel (24.7%) and cilta-cel (38.2%) were administered intravenous immunoglobulin (IVIG) from 6 months before the index date to 30 days after administration. Over the full study period, the majority of patients receiving ide-cel (64.0%) and cilta-cel (77.1%) were administered IVIG. Healthcare costs related to HCRU and HCRU rates over 6 months of follow-up will also be reported.Conclusions: In real-world settings,CAR-T administration primarily occurred in the inpatient setting and lasted a mean of >2 weeks, including time in the ICU. During the 30 days post-administration period, some patients required additional acute care services, often due to hematologic toxicity or CRS. A substantial percentage of patients had IVIG pre- or post-administration; however, infections were still observed during the 30 days post administration. These findings inform patient care planning and resource allocation in CAR-T implementation.

AIMS:Evaluate treatment and outcomes by social determinants of health (SDoH) in multiple myeloma (MM), which are important for improving care and outcomes. METHODS:This was a retrospective study of real-world patients enrolled in a US insurance claims database (MM diagnosis, July 2018-December 2022) with linkage to a SDoH database, supplemented with mortality, provider affiliation (academic/community), and socioeconomically disadvantaged area databases. Treatment and outcomes were evaluated across SDoH domains: race/ethnicity, education level, transportation access, food insecurity, risky health behaviors, living in disadvantaged areas, healthcare needs, and ease of healthcare-systems engagement. RESULTS:The study included 4768 patients (2295 and 2731 with care-setting and treatment data); median follow-up, 584 days. Patients treated in academic versus community settings were less likely to be food insecure and live in disadvantaged areas and had lower healthcare needs. Stem cell transplant was more common in White versus non-White patients, those with low versus high food insecurity and healthcare needs, and high versus low ease of healthcare-systems engagement. In multivariable analysis, high versus low disadvantaged areas (HR = 1.75) and medium versus low food insecurity (HR = 1.80) were associated with shorter overall survival. CONCLUSIONS:These findings indicate a need for improved access to care in the broader MM population.

In the Phase 3 DREAMM-7 study of patients with relapsed/refractory multiple myeloma (RRMM) who received ≥ 1 prior therapy, belantamab mafodotin plus bortezomib and dexamethasone (BVd) demonstrated a progression-free survival (PFS) benefit versus daratumumab plus bortezomib and dexamethasone (DVd). This study aimed to indirectly compare the efficacy of BVd against alternative regimens in this patient population. A systematic literature review (SLR; December 2021-February 4, 2024) was performed to identify relevant efficacy data. Studies were selected based on the Population-Intervention-Comparators-Outcomes-Study design framework criteria and independently reviewed for inclusion in the network meta-analysis (NMA) if they had a connection to DREAMM-7 (approved in the US or EU, or likely to be a future DREAMM-7 comparator). Each trial had a common comparator arm, allowing for a connected network between the trials and linkage by shared treatments. The primary analysis was PFS in the intent-to-treat population from each study, and secondary analyses examined other endpoints. All endpoints were also evaluated in subgroups by lenalidomide-exposure, -refractoriness, and other patient characteristics. The SLR identified 12 comparator studies comprising 12 comparator regimens (each contained a proteasome inhibitor [bortezomib or carfilzomib] plus dexamethasone), all of which were included in the NMA with the DREAMM-7 study. BVd improved PFS versus all comparators, including daratumumab plus carfilzomib and dexamethasone, isatuximab plus carfilzomib and dexamethasone, and DVd. Overall survival was also improved by belantamab mafodotin plus bortezomib and dexamethasone over the other regimens. This study provides compelling evidence for belantamab mafodotin, plus bortezomib and dexamethasone, in early lines of treatment for RRMM.

AIM:Evaluate multiple myeloma (MM) treatment patterns, healthcare utilization (HCRU), and costs from academic and community settings. METHODS:This observational study linked US MM insurance claims (1 April 2017-30 June 2022) with provider affiliations to evaluate patient characteristics and treatment durations across patient cohorts defined by care setting of treatment (academic only, community only, mixed [both]), as well as treatment patterns, HCRU, and costs of care (e.g. treatment, office visits, hospitalization) in each setting. RESULTS:3778 patients were included. By cohort (n = 530 academic; n = 1647 community), the community cohort was older with more comorbidities. Mixed-cohort patients (n = 1601) frequently initiated treatment at community centers and briefly shifted to academic centers for transplant. Among 3778 patients who received MM-related care, most claims were from the community setting. The academic setting had high rates of claims for proteasome inhibitors (56.3% of patients) and steroids (52.5%); the community setting had high rates for immunomodulatory drugs (75.1%) and steroids (85.0%). Stem cell transplant claims were more common for academic versus community (21.4%/7.3%). Treatment duration/time to next therapy were similar between cohorts. Costs were generally higher in the academic versus community settings. CONCLUSION:Improved patient support is needed in community settings, where most MM care occurs.

Introduction: Bispecific antibodies (BsAbs) including teclistamab (tec), talquetamab (talq), and elranatamab (elra) have emerged as treatment options for multiple myeloma (MM). Real-world data are needed to characterize patients who receive these treatments and their healthcare resource utilization (HCRU), which may help guide clinical decision making. Here we report the real-world demographics, administration-related HCRU, and post-administration HCRU of patients who received tec, talq, or elra. Methods: This was a retrospective cohort study that used the IQVIA PharMetrics Plus® Enhanced Closed Claims database. Adults with MM were included if they were not participating in clinical trials and had a first observed claim for tec, talq, or elra starting with their respective FDA-approval month (tec, Oct 1, 2022; talq and elra, Aug 1, 2023). Continuous enrollment in medical and pharmacy benefits for ≥6 months before and ≥1 month after the step-up dosing index period (defined as the first 7 days of BsAb treatment administration, following label recommendation of 3 step-up doses) was required. Patient demographics were evaluated in the 6 months prior to or during the index period. Administration-related HCRU was evaluated during the index period and post-administration HCRU was evaluated during the 30 days following the index period. Study periods were from Apr 1, 2022 (tec)/Feb 1, 2023 (talq and elra) until Sep 30, 2024. Results: The tec cohort included 405 patients, the talq cohort included 78 patients, and the elra cohort included 26 patients. Median (interquartile range) ages were 66 (59–74) years for tec, 62 (55–70) years for talq, and 67 (59–78) years for elra. Most patients were male (58.3/62.8/46.2% tec/talq/elra). During the step-up dosing index period, all-cause inpatient admissions were observed for 39.3/10.3/15.4% of patients treated with tec/talq/elra and lasted for a mean (standard deviation [SD]) of 10.1 (7.3)/10.6 (7.5)/5.1 (2.1) days. Emergency room (ER) visits were recorded for 2.5/1.3/19.2% of patients treated with tec/talq/elra. Intensive care unit (ICU) stays were observed for 8.9/7.7% of patients treated with tec/elra, lasting a mean (SD) of 8.3 (6.4)/5.5 (3.5) days, but did not occur in patients treated with talq. In the 30-day post-index period for tec/talq/elra, 19.8/23.1/34.6% of patients had ≥1 all-cause inpatient admission, with 8.4/10.3/11.5% having an ICU stay and 14.3/12.8/34.6% having an ER visit; lengths of stay for tec/talq/elra were a mean (SD) of 9.2 (6.1)/11.9 (9.2)/7.3 (6.9) days for inpatient stays and 10.7 (7.3)/15.9 (11.9)/9.3 (7.8) days for ICU stays. The most frequent diagnoses in the 30 days after tec/talq/elra administration were hypogammaglobulinemia (28.4/32.1/46.2%), hypertension (35.6/21.8/38.5%), and hematologic complications (35.8/41.0/30.8%), which included neutropenia, anemia, thrombocytopenia, and leukopenia. Inpatient admissions related to hypogammaglobulinemia occurred in 7.4/5.1/19.2% of patients receiving tec/talq/elra. Inpatient admissions related to hypertension occurred in 17.3/10.3/19.2% of patients receiving tec/talq/elra. Inpatient admissions related to hematologic complications occurred in 18.8/14.1/15.4% of patients receiving tec/talq/elra. Infections in the 30 days after tec/talq/elra step-up dosing occurred in 14.3/15.4/26.9%. In total, 36.0/52.6/38.5% of patients who received tec/talq/elra were administered intravenous immunoglobulin (IVIG) from 6 months before the index date to 30 days after administration, which increased to 67.9/65.4/50.0% during the full study period. Healthcare costs related to HCRU and HCRU rates over 6 months of follow-up will also be reported. Conclusions: Inpatient visits and ICU stays were required for patients during step-up dosing and the subsequent 30 days, and these generally lasted >1 week. Approximately half of the patients who experienced hypertension or hematologic complications required inpatient admission during the 30 days following step-up dosing. The majority of patients had IVIG before, during, or after step-up dosing; however, a substantial percentage of patients had hypogammaglobulinemia and noticeable percentages of infections were still observed shortly after initiating the treatment.

e20046 Background: A prior retrospective analysis of US patients (pts) with RRMM suggested that pts treated with belamaf, a BCMA-targeting antibody-drug conjugate, experienced similar outcomes to those who received belamaf in the pivotal DREAMM-2 study. This updated analysis aimed to characterize pts, assess occurrence and management of ocular adverse events (AEs), and evaluate belamaf effectiveness in a real-world setting. Methods: This retrospective, longitudinal, observational study used data sourced from the US EHR-derived Flatiron Health de-identified database (01/01/2011–06/30/2022). Eligible pts had a confirmed MM diagnosis, initiated belamaf after FDA approval (08/05/2020; first administration=index date), were ≥18 years old at index, and had chart abstraction data for ocular safety and treatment effectiveness. Data on ocular AEs were reported separately for all pts and pts with ≥4 months (mo) of follow-up to allow for sufficient follow-up to evaluate incidence of ocular AEs and their mitigations. Tumor response was assessed in all pts, along with Kaplan-Meier estimates of duration of response (DoR), overall survival (OS), and progression-free survival (PFS). Results: Of the 184 pts included in the study, mean age was 68.7 years; 64% were White and 47% were female. Eastern Cooperative Oncology Group (ECOG) status was ≥2 in 28% patients, 62% had received ≥5 prior lines of therapy, and 82% were triple-class refractory. Median (IQR) follow-up was 4.1 (1.9–8.5) mo. Among pts with ≥4 months of follow-up (n=94) 75% had ≥1 ocular AE, with keratopathy and blurred vision being the most frequent. Mean (SD) time to first ocular AE was 39 (34) days. Most ocular AEs were managed by therapy hold (69%; of which 73% restarted belamaf) and/or AE treatment (63%). The median dose hold due to ocular AEs was 43 days (physician-reported keratopathy: mild, 21 days; moderate/severe, 56 days). In all pts, 39 (21%) had a derived tumor response based on serum free light chain levels, (partial response: 74%, very good partial response: 51%). For all pts, the estimated median DoR was 9.1 mo, PFS 4.5 mo, and OS 7.9 mo, while the 6-month DoR rate was 57%, PFS rate was 46%, and OS rate was 58%. Conclusions: Overall, belamaf was effective in the real world setting in heavily pre-treated pts with RRMM and limited therapy options. The AE profile was consistent with DREAMM-2. Ocular AEs were manageable and despite their occurrence, a high percentage of pts remained on treatment, suggesting belamaf may fill an unmet need for triple-class refractory pts with RRMM. [Table: see text]

Introduction:Anti-CD38-based therapy has become a backbone regimen for the treatment of multiple myeloma (MM), approved in first-, second-, and third-line settings. The effectiveness of anti-CD38-based retreatment after an initial relapse on previous anti-CD38-based therapy is unclear. Here we present the results of a systematic literature review investigating the clinical outcomes of anti-CD38-based retreatment in patients with relapsed/refractory MM. Methods:Medline/Embase, congress publications, and other sources were searched (to December 8, 2023) for relevant articles in English and screened for eligibility criteria using the Population, Intervention, Comparator, Outcomes, Study Design (PICOS) framework, and data were then extracted for outcomes including progression-free survival (PFS), overall survival (OS), and overall response rate (ORR). Results:In total, 2938 records were identified from the initial Medline/Embase search and 11 were identified from other sources; 34 were eligible for inclusion, representing 24 studies (6 clinical [n=18-307] and 18 real-world evidence [RWE; n=19-583]). Where reported, median follow-up ranged from 1.9-43.0 months across 6 clinical and 8.7-53.0 months across 10 RWE studies. For clinical trials, anti-CD38-based retreatment resulted in a median PFS of 1.0-2.8 months in all but one trial (19.4 months), a median OS of 10.7-19.1 months (not reached in one trial), and ORRs of 0-75%. RWE studies reported a median PFS of 1.5-8.4 months, a median OS of 8.4-19.0 months (not reached in one study), and ORRs of 24.6-90.0%. Discussion:Findings from this systematic literature review indicate that clinical outcomes with anti-CD38-based retreatment are variable and offer limited clinical benefit in patients with relapsed/refractory MM, including in those refractory to anti-CD38-based treatment.

In the ongoing global, open-label, randomized phase 3 DREAMM-7 study (NCT04246047), belantamab mafodotin, bortezomib, and dexamethasone (BVd) demonstrated significant and clinically meaningful progression-free survival (PFS) benefit (median follow-up, 28.2 months; hazard ratio [HR], 0.41; 95% CI, 0.31-0.53; P<0.001), as well as early and sustained overall survival (OS) benefit (median follow-up, 39.4 months; HR, 0.58; 95% CI, 0.43-0.79; P=0.0002), vs daratumumab, bortezomib, and dexamethasone (DVd) in patients with relapsed/refractory multiple myeloma (RRMM) who received ≥1 prior line of therapy. With other emerging, heterogenous treatment options for RRMM, critical assessment of the comparative efficacy of BVd vs alternative therapies is warranted to inform clinical practice and health policy decisions. However, the relapsing nature of multiple myeloma (MM) leads to limited follow-up time in randomized clinical trials and challenges in estimating long-term OS. Therefore, we estimated the expected long-term OS/life-years (LYs) and quality-adjusted LYs (QALYs) over the lifetime of patients treated with BVd compared with other alternative therapies for MM at first relapse. To evaluate BVd vs proteasome inhibitor–based alternative therapies, a de novo partitioned survival model was developed with the health states progression-free disease, progressed disease, and death; the starting age of patients in the model was 64 years, and a time horizon of 36 years was used to estimate lifetime LYs and QALYs. For overall LYs, efficacy data for BVd and DVd were sourced from DREAMM-7, while relative treatment effects of nontrial alternative therapies were informed by a published network meta-analysis. Parametric survival models were used to extrapolate PFS and OS for BVd and DVd; clinicians were asked to estimate the OS for BVd and DVd at 5, 10, and 15 years following treatment initiation, to validate the long-term survival extrapolation and ensure alignment with clinical expectations. HRs were applied to the DVd OS curve to estimate PFS and OS for the nontrial alternative therapies. To estimate QALYs for each treatment, health state utilities were informed by DREAMM-7 EQ-5D-3L data and adjusted for adverse event (AE) disutilities; the proportion of patients with grade ≥3 AEs based on trial data was used to calculate the disutilities for each alternative therapy. BVd led to more LYs (12.0) and QALYs (9.8) compared with all alternative therapies (carfilzomib and dexamethasone [Kd], 8.1 and 6.6, respectively; daratumumab and Kd [DKd], 10.1 and 8.2; isatuximab and Kd [IsaKd], 10.1 and 8.2; bortezomib and dexamethasone [Vd], 6.0 and 4.9; pomalidomide and Vd, 8.1 and 6.6; selinexor and Vd, 7.3 and 5.9; DVd, 8.8 and 7.2). Estimated probability of survival at 5 years using the model was higher for BVd (64%) vs all alternative therapies (range, 34% [Vd] to 53% [DKd and IsaKd]). BVd led to substantially more LYs and QALYs compared with alternative treatment regimens for RRMM, highlighting the potential of BVd to extend survival and enhance clinical and quality-of-life benefits for these patients. These insights are critical to support clinical and health policy decision-making in MM at first relapse, supporting the use of BVd as a standard of care in this population. Drug-linker technology licensed from Seagen Inc; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa.

Introduction: Costs associated withadministration and adverse events (AEs) are important considerations in budget impact models (BIMs) of anti-cancer therapies. Anti-BCMA antibody-drug conjugates (belantamab mafodotin [belamaf]), chimeric antigen receptor T-cell therapies (CAR-T; ciltacabtagene autoleucel [cilta-cel], idecabtagene vicleucel [ide-cel]), and bispecifics (teclistamab) for relapsed/refractory multiple myeloma (RRMM) vary in modes of administration and AE burden; characterizing associated costs may support payer decision making. The study aimed to compare administration and AE-related costs of belamaf regimens with those of other anti-BCMA agents using BIM. Methods: A 3-year BIM was developed to evaluate administration and AE-related costs for patients with RRMM and ≥1 prior line of therapy who had received belamaf plus bortezomib and dexamethasone (BVd), belamaf plus pomalidomide and dexamethasone (BPd), cilta-cel, ide-cel, or teclistamab. Administration costs included office visits, drug delivery, label-required hospitalization, premedication (including intravenous immunoglobulin), and for CAR-T, leukapheresis and bridging therapies sourced from published protocols, labels, or clinician input. Administration-related unit costs were sourced from the 2025 Medicare Physician Fee Schedule, Medicare Procedure Price lookup for leukapheresis, literature for hospitalization costs, and Medi-Span Price Rx for wholesale acquisition costs for drug costs. BVd/BPd dosing was obtained using weekly individual patient dosing data from DREAMM-7/DREAMM-8 trials (means of 9/7/6 doses for BVd and 6/3/3 doses for BPd in Years 1/2/3) and cilta-cel/ide-cel/teclistamab dosing from published prescribing information. AE-related costs included grade ≥3 AEs with ≥5% incidence, as well as grade ≥2 ocular AEs (oAEs) for belamaf obtained from clinical trial publications. Grade ≥2 cytokine release syndrome (CRS) for CAR-T/bispecific therapies was included with an assumption that costs of treating CRS of Grade 2 or 3 are the same on average. Median durations of treatment input into the BIM were obtained from Kaplan-Meier analyses of second-line or later clinical trials for BVd (17.3 months), BPd (20.0 months), and cilta-cel (45.4 months), and from third-line or later clinical trials for teclistamab (8.5 months) and ide-cel (13.3 months); use of third-line or later clinical trials for median duration of therapy may have impacted on the estimated costs. The costs associated with treatment of AEs were based on Healthcare Cost and Utilization Project data for inpatient treatment. The assessment was conducted from a Medicare plan perspective, with costs (in 2025 USD) annualized over 3 years and reported as mean costs per patient. Results: Three-year cumulative administration costs were $1,699 (BVd), $1,024 (BPd), $67,119 (teclistamab), $103,625 (ide-cel), and $103,625 (cilta-cel). The most common grade ≥3 AEs were thrombocytopenia (55%/38%) and neutropenia (12%/57%) for BVd/BPd, and neutropenia (64%/76%/90%) and thrombocytopenia (21%/42%/41%) for teclistamab/ide-cel/cilta-cel. Grade ≥2 oAEs occurred in 81%/82% with BVd/BPd. Grade ≥2 CRS occurred in 22% (teclistamab)/32% (ide-cel)/23% (cilta-cel). AE-related costs were $19,396 (BVd), $24,168 (BPd), $51,216 (teclistamab), $83,521 (ide-cel), and $62,292 (cilta-cel). Alternative assumptions and sensitivity analyses were explored.Conclusions: BVd/BPd had substantially lower administration and AE-related costs vs CAR-T and bispecific therapies, which have high costs mostly due to hospitalizations, premedication, and CRS rates.

Introduction: Patients with relapsed/refractory multiple myeloma(RRMM) who are refractory to lenalidomide (len) have limited effective treatments and consequently poor outcomes. The phase III DREAMM-7 study (NCT04246047) evaluated belantamab mafodotin (B), an antibody-drug conjugate targeting B-cell maturation antigen, with bortezomib (V)+dexamethasone (d; BVd) vs daratumumab (D)+Vd (DVd) in patients with RRMM who had ≥1 prior line of therapy (2L+) and included patients who were len-exposed/refractory (Hungria et al. NEJM 2024). In the ITT analysis, BVd improved progression-free survival (PFS) vs DVd (36.6 vs 13.4 months; hazard ratio [HR] 0.41, 95% confidence interval 0.31-0.53, P<0.00001). The PFS benefit was maintained in all predefined subgroups, including prior len-exposed, len-refractory, 2L-only, and high-risk cytogenetic patients. In the absence of head-to-head trials, indirect comparisons can evaluate the relative efficacy of BVd compared with other regimens for RRMM in 2L+, including subpopulations of clinical interest, to better inform treatment decisions. A prior network meta-analysis (NMA) suggested BVd improved PFS in 2L+ RRMM compared with other proteasome inhibitor (PI)-based regimens (Richter 2024, IMS). Here, a similar analysis was performed in len-exposed, len-refractory, 2L-only, and high-risk cytogenetic subpopulations. Methods: A systematic literature review identified randomized controlled trials (RCTs) (Jan 2008-Feb 2024) of adults with RRMM in 2L+ who had disease progression on/after most recent therapy. Only RCTs that evaluated PFS in a regimen approved/likely to be approved by the US Food and Drug Administration/European Medicines Agency, or which were of interest for health technology assessment, were included. Trials/regimens that were not part of the connected evidence networks were excluded from the NMA. Trials were linked together by the treatment(s) they shared to form connected networks of evidence, and a Bayesian NMA was conducted to assess PFS. NMAs were constructed based on the availability of regimen data within the networks for each subpopulation of interest (2L+ len-exposed, len-refractory, 2L-only and high-risk cytogenetic). Results: All regimens compared with BVd were PI-based regimens. The len-exposed subpopulation network comprised 8 RCTs and included the following regimens: BVd, DVd, carfilzomib (K)+ d (Kd; plus an alternative dosage), DKd, isatuximab (Isa)+ Kd (IsaKd), pomalidomide (P)+ Vd (PVd), selinexor (S)+Vd (SVd), and Vd. BVd improved PFS across all comparators, and HRs (range 0.12‒0.34) were statistically significant in favor of BVd. HRs (95% credible interval [CrI]) for BVd compared with anti-CD38 regimens included 0.34 (0.17-0.71) vs DKd, 0.29 (0.13-0.64) vs IsaKd, and 0.29 (0.19-0.43) vs DVd. The len-refractory subpopulation network comprised 8 RCTs with the same regimens as the len-exposed population except SVd and the addition of cyclophosphamide (Cy)+ Kd (CyKd). BVd improved PFS across all comparators, and HRs were statistically significant favoring BVd, ranging from 0.14‒0.38. HRs (95% CrI) for BVd compared with anti-CD38 regimens included 0.37 (0.15-0.89) vs DKd, 0.29 (0.12-0.70) vs IsaKd, and 0.31 (0.20-0.49) vs DVd. The 2L-only subpopulation network comprised 10 RCTs, with the same treatments as the len-exposed subgroup plus panobinostat + Vd and elotuzumab (E) + Vd. BVd improved PFS across all comparators and HRs (range 0.13‒0.52) were statistically significant favoring BVd. HRs (95% CrI) for BVd compared with anti-CD38 regimens included 0.45 (0.21-0.94) vs DKd, 0.42 (0.20-0.88) vs IsaKd, and 0.52 (0.36-0.76) vs DVd. The high-risk cytogenic subpopulation network comprised 10 RCTs, with the same treatments as the len-exposed subgroup plus CyKd. BVd improved PFS across all comparators, and HRs (range 0.13‒0.40) were statistically significant favoring BVd except vs DKd. HRs (95% CrI) for BVd compared with anti-CD38 regimens included 0.40 (0.15-1.09) vs DKd, 0.27 (0.10-0.71) vs IsaKd, and 0.31 (0.18-0.53) vs DVd. Conclusions: The DREAMM-7 RCT demonstrated a significant PFS benefit with BVd vs DVd in patients with ≥1L RRMM. In the absence of RCT comparing BVd to regimens (besides DVd), this NMA indicates that BVd offers improved PFS compared with other PI-based regimens for subpopulations of patients with RRMM who are len-exposed/refractory, in 2L-only, or with high-risk cytogenetic profiles.