Hansen, Doris K.

Introduction: Recent efforts have shed light on the clinical and laboratory factors associated with toxicity and response to BCMA-directed CAR-T therapy in patients with relapsed/refractory multiple myeloma (RRMM). However, a major limitation of current scoring systems lies in their assessment at time of lymphodepletion. Because they are not determined before apheresis, they are ill-equipped to guide patient selection, anticipate level-of-care, or plan pre-emptive toxicity management strategies. We therefore aimed to characterize early predictors of CAR-T toxicity and response. Study Design: In this multicenter observational study, we examined demographic, clinical, and laboratory data across three distinct timepoints: indication (e.g., treatment decision), apheresis, and pre-lymphodepletion (LD). CRS and ICANS were graded according to ASTCT criteria. Hematotoxicity (ICAHT) was graded using EHA/EBMT criteria. Early infections (day 0-100) were defined based on microbiologic data or as a clinical infection syndrome, and graded per Hill et al, Blood 2018. Kaplan-Meier estimates of progression-free (PFS) and overall survival (OS) were compared by log-rank test. Cox proportional hazard models were applied to explore associations between pre-apheresis risk factors and key toxicity and survival outcomes. The CAR-HEMATOTOX (HT) score - encompassing markers of inflammation (e.g., CRP, ferritin) and marrow reserve (e.g., hemoglobin, ANC, platelet count) - was determined at each timepoint (Rejeski et al, Blood 2021). Results: We included 530 RRMM patients treated with standard-of-care cilta-cel (n=184) or ide-cel (n=346) across nine centers. Median age was 65 (range 31-88), median ECOG was 1 (IQR 0-1), and patients received a median of 5 prior lines of therapy (IQR 4-7). The median time from indication to apheresis was 16 days (IQR 7-52), while the median time from apheresis to infusion was 56 days (IQR 46-69). The proportion of high-risk patients by HT score did not change between the pre-apheresis and LD timepoints (19% vs. 20%, p=0.82). Most patients stayed either low-risk (n=388, 73.2%) or high-risk (n=68, 12.8%). However, 35 patients (6.6%) shifted from high-to-low risk, while 39 patients (7.4%) progressed from low-to-high risk - reflecting their response to bridging therapies. We noted considerable differences in morbidity and mortality based on the pre-apheresis HT score. Compared to their low-risk counterparts (score 0-2, n=427), high-risk patients (score ≥3, n=103) were hospitalized longer (12 vs. 15 days, p=0.009) and required more frequent ICU admissions (6% vs. 12%, p=0.05). They exhibited more severe early cytopenias (G3+: 8% vs. 25%, p<0.001) and late cytopenias (G3+: 7% vs. 21%, p<0.001), resulting in increased use of TPO agonists and stem cell boosts. Grade 3 or higher ICANS was also more common in HThigh patients (3% vs. 11%, p=0.006), as were severe infections (14% vs. 27%, p=0.007). We found increased non-relapsed mortality in HThigh patients (1-yr NRM 4.6% vs. 16.1%, p<0.001), but no significant difference in the occurrence of secondary malignancies (p>0.9). With a median follow-up of 12.4 months, HThigh patients showed inferior PFS (1-yr PFS 29% vs. 63%, p<0.0001) and OS (1-yr OS 49% vs. 83%, p<0.0001). Transitioning from a low-to-high score was linked to poor survival (1-yr PFS 26%), while the shift from high-to-low risk was associated with favorable outcomes (1-yr PFS 51%). In a multivariable Cox regression model of pre-apheresis features, a high HT score (aHR 2.52, p<0.0001), prior anti-BCMA therapy (aHR 1.55, p=0.04), history of extramedullary disease (aHR 1.42, p=0.02), and penta-refractoriness (aHR 1.45, p=0.02) were independently associated with PFS. Notably, the presence of more than 3 of these high-risk features defined an ultra-high-risk cohort of 28 patients (5.3%) with particularly dismal survival (1-year PFS 15%). Conclusions: Leveraging granular pre-apheresis data from a large international cohort, we identify early markers of toxicity and response in CAR-T-treated RRMM patients. The HT score - reflecting baseline inflammation and hematopoietic reserve - identified high-risk patients likely to benefit from pre-emptive toxicity mitigation strategies such as prophylactic stem cell collection. Most importantly, we characterize a small yet ultra-high-risk group of RRMM patients in need of more effective bridging and therapeutic options.

Background: Tec is a BCMA-directed bispecific antibody (BsAb) approved for RRMM after ≥4 prior lines of therapy (LOT) based on the MajesTEC-1 trial. However, patients who had previously received a BCMA-DT were excluded from MajesTEC-1. Herein, we evaluated outcomes of RRMM patients with prior exposure to BCMA-DT treated with standard-of-care Tec. Methods: This was a multicenter retrospective cohort study. We compared variables between different groups using Chi-squared and Kruskal-Wallis tests, and assessed progression free survival (PFS) and overall survival (OS) using Kaplan Meier and Cox proportional hazards model. We used the maximally selected rank statistics method to determine the optimal cut-off point for continuous variables to find the most significant difference in PFS among different groups. Results: A total of 385 patients were included in this study. 193 patients had received a prior BCMA-DT, of whom 77%, 22%, and 1% had received 1, 2, and 3 prior anti-BCMA agents, respectively. In patients who had received a prior BCMA-DT, 35% were aged ≥70 years, 24% had ECOG performance status (PS) ≥2, 61% had high-risk FISH, 32% had extramedullary disease (EMD) at Tec initiation, and 42% were penta-refractory. Compared to the cohort without prior BCMA-DT (n=192), patients who were treated with prior BCMA-DT were more likely to have high risk FISH (61% vs 49%, p=0.02), and higher median number of prior LOT (7 vs 5, p <0.001). The specific types of prior BCMA-DTs with the respective overall response rate (ORR) to the most recent prior BCMA-DT were: antibody drug conjugate only (ADC, n=47, ORR 43%), chimeric antigen receptor T-cell therapy only (CAR T, n=99, ORR 86%), BsAb only (n=6, ORR 100%), ADC + CAR T (n=36, ORR 56%), and other ADC/CAR T/BsAb combinations (n=5, ORR 60%). Median follow up was 9.9 (95% CI:9.5-10.6) months. Patients with prior receipt of BCMA-DT had a lower ORR (51.4% vs 61.5%; p=0.012) and ≥very good partial response rate (39.4% vs 52.6%, p=0.009), but similar ≥complete response rate (22.3% vs 24%; p=0.78) to Tec compared to those without prior BCMA-DT. Moreover, patients with prior BCMA-DT had worse median PFS compared to patients without prior BCMA-DT (prior BCMA-DT: 4.6 months, 95% CI: 2.7-7.5; without prior BCMA-DT: 8.2 months, 95% CI: 5.7-12.2; p=0.017). On multivariable analysis incorporating prior BCMA-DT, age, cytogenetics, EMD, and ECOG PS, receipt of prior BCMA-DT was not independently associated with PFS (HR 1.25, 95% CI 0.95-1.64, p=0.1). The estimated 1-year OS rate was 58.9% (95% CI: 51.64-67.2) for the prior BCMA-DT group vs 65.1% (95% CI: 58.1-73.1) for the group without prior BCMA-DT, p=0.16. For the prior BCMA-DT cohort, response rates to Tec were numerically higher in patients who received CAR T (ORR 51.2%) followed by ADC (ORR 45.5%), and bispecific (ORR 30%) as their most recent prior BCMA-DT (p=0.39). No significant difference in PFS was noted when stratifying patients by number of prior BCMA-DTs, types of all prior BCMA-DTs received, type of most recent prior BCMA-DT, or depth of response to most recent BCMA-DT. Patients who responded to Tec had a numerically longer median time from most recent BCMA-DT exposure to Tec initiation compared to non-responders: 10.5 vs 7.5 months, p=0.48. We found that the optimal cut-off for time from last BCMA-DT exposure to Tec initiation was 8.7 months. Patients with > 8.7 months between last exposure to prior BCMA-DT and Tec initiation had a superior median PFS with Tec (8.1 months, 95% CI: 4.6-11.7) compared to patients with < 8.7 months from last exposure to prior BCMA-DT (2.5 months, 95% CI: 1.1-5.7), p=0.001. The toxicity profile for patients with prior BCMA-DT was similar to those who had not received a prior BCMA-DT. Grade ≥2 CRS occurred in 8.7% vs 13% (p=0.18), and grade ≥2 ICANS in 7.7% vs 6.7%, (p=0.85) of patients with and without prior BCMA-DT, respectively. Patients in the prior BCMA-DT cohort were more likely to have grade 3 thrombocytopenia in the first 30 days after Tec initiation (10.7% vs 6.6%; p=0.08). Conclusion: This is the largest study to date of any BCMA-directed BsAb among BCMA-exposed patients. Receipt of prior BCMA-DT was associated with a trend toward worse PFS, although not statistically significant, and lower likelihood of attaining an overall response. Waiting >9 months between sequencing BCMA therapies may be associated with improved PFS. D.D., M.A.V.M., J.A.D: co first authors; F.A., C.F., L.S.: co senior authors

Introduction: Anti-BCMA CAR-T therapies like idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) have revolutionized RRMM treatment. However, the 6-8-week manufacturing period often leads to disease progression and/or death in up to 25% of patients (pts), necessitating effective bridging strategies. Talquetamab (talq), a bispecific antibody targeting GPRC5D, is approved for RRMM pts with four prior lines of therapy and offers rapid disease debulking without impacting BCMA. This study assesses the safety and efficacy of a short course of talq as a bridging therapy for pts receiving cilta-cel or ide-cel. Methods: This multicenter retrospective study involved 14 US academic medical centers within the US Multiple Myeloma Immunotherapy Consortium. We included pts with RRMM who underwent leukapheresis and received talq bridging therapy with the intent to proceed to commercial cilta-cel or ide-cel. We assessed the safety, feasibility, and efficacy of talq bridging therapy. Safety outcomes included cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), talq-related unique toxicities, and delayed neurotoxicity (NT). Efficacy outcomes included response rates to talq and CAR-T therapies. Results: Between June 2023 and May 2024, 77 pts received talq bridging therapy after apheresis with the intention to proceed to CAR-T. The median age was 66 years (range, 58-73); 14% were Black and 10% Hispanic. Poor prognostic features, including high-risk cytogenetics, were present in 45%, extramedullary disease (EMD) in 43%, and 72.7% were triple-class refractory. The median number of prior lines of therapy was 5 (range 3-11) and 10 pts (13%) had prior BCMA targeted therapy. Out of 77 pts, 10 pts were pending CAR-T infusion at the time of last follow up; 6 pts could not receive CAR-T infusion due to manufacturing failures. Of the remaining 61 patients who underwent successful CAR-T manufacturing, 58 (95%) pts were successfully infused with CAR-T therapy following talq bridging. Three (5%) pts died due to disease progression prior to CAR-T infusion. Talq was given 0.8 mg/kg biweekly in 59 (76%) pts and the median time on talq was 22 days (IQR: 10-41 days). Following talq bridging, none of the pts had grade >=3 CRS and 2 (2.5%) had grade 3 ICANS. Skin toxicities occurred in 32 (41%), nail toxicities in 19 (25%), and oral toxicities in 43 (56%) pts mainly grade 1. Most oral, skin, and taste changes resolved at the last follow-up (60%). Response to talq was evaluable in 72 out of 77 patients. An overall response was noted in 45/72 (62%) pts including unconfirmed CR in 14, VGPR in 10 and PR in 21 pts. There was no association of AEs and response to talq with high-risk cytogenetics, EMD and high baseline ferritin levels. Out of the 58 patients who went on to receive CAR-T therapy following talq bridging (45 cilta-cel and 13 ide-cel), 38 (65%) experienced CRS, with grade 3 CRS noted in 2 (3%) pts. ICANS occurred in 5 (8.6%) pts, with 1 (1.7%) grade 3 ICANS. Only 1 pt had delayed NT (facial nerve palsy) at the last follow up. No treatment related deaths were observed. Of these 58 pts, response was evaluable in 40 pts and a response at day +30 was noted in 39/40 (97.5%) pts (14 in CR, 10 in VGPR, 15 in PR). The median follow-up from CAR-T was 61 days (28-113). For the 58 pts who received CAR-T, the median time from the last talq dose to CAR-T infusion was 25 days (IQR: 19-36), and to lymphodepletion was 24 days (IQR: 18-33). There was no difference in the CAR-T related AEs by the duration of Talq washout (>4 weeks vs. =< 4 weeks). Conclusions: Talquetamab is an excellent bridging option before BCMA-targeted CAR-T therapy, showing high response rates even with short-term use and enabling most pts to receive CAR-T. Most oral, skin, and taste changes resolved post CAR-T. These findings underscore the effectiveness of a short course of talq bridging to maintain disease control and improve outcomes post CAR-T. Updated data with longer follow-up will be presented at the meeting.

ABSTRACT Introduction Daratumumab, lenalidomide, and dexamethasone (DRd) and bortezomib, lenalidomide, and dexamethasone (VRd) are the only preferred treatment regimens for patients with transplant‐ineligible (TIE) newly diagnosed multiple myeloma (NDMM). As there are no randomized head‐to‐head studies of DRd versus VRd, this analysis aimed to compare real‐world time‐to‐next‐treatment (TTNT) or death in this population. Methods Patients with NDMM who received front‐line (FL) DRd or VRd were identified from the Acentrus database (January 1, 2018 to May 31, 2023). Those with a record of a stem cell transplant or aged < 65 years were excluded to limit analysis to the TIE population. Inverse probability of treatment weighting was used to balance baseline patient characteristics. A doubly robust Cox proportional hazards model was used to compare TTNT or death between cohorts. Results A total of 149 and 494 patients who initiated DRd and VRd, respectively, were identified. After weighting (weighted N DRd = 302, weighted N VRd = 341), cohorts had similar baseline characteristics. Of these, 98 (32.4%) DRd and 175 (51.2%) VRd patients either received a subsequent line of therapy or died, with a median TTNT or death of 37.8 months in the DRd cohort and 18.7 months in the VRd cohort (hazard ratio: 0.58, 95% confidence interval: 0.35, 0.81; p < 0.001). Conclusion Treatment of TIE NDMM patients with DRd led to a significantly longer TTNT or death compared to VRd, evidenced by a 42% risk reduction, supporting the effectiveness of DRd over VRd as FL treatment in this patient population.

Abstract Ciltacabtagene autoleucel (cilta-cel) was approved in 2022 for patients with relapsed/refractory multiple myeloma (RRMM). We report outcomes with cilta-cel in the standard-of-care setting. Patients with RRMM who underwent leukapheresis for cilta-cel manufacturing between 1 March 2022 and 31 December 2022 at 16 US academic medical centers were included. Overall, 255 patients underwent leukapheresis and 236 (92.5%) received cilta-cel, of which 54% would not have met CARTITUDE-1 eligibility criteria. In treated patients (N = 236), cytokine release syndrome was seen in 75% (grade ≥3, 5%), immune effector cell–associated neurotoxicity syndrome in 14% (grade ≥3, 4%), and delayed neurotoxicity in 10%. Overall and complete response rates were as follows: all patients who received cilta-cel (N = 236), 89% and 70%; patients receiving conforming cilta-cel (n = 191), 94% and 74%; and conforming cilta-cel with fludarabine/cyclophosphamide lymphodepletion (n = 152), 95% and 76%, respectively. Nonrelapse mortality was 10%, most commonly from infection. After a median follow-up of 13 months from cilta-cel, the median progression-free survival (PFS) was not reached, with 12-month estimate being 68% (95% confidence interval, 62-74). High ferritin levels, high-risk cytogenetics, and extramedullary disease were independently associated with inferior PFS, with a signal for prior B-cell maturation antigen–targeted therapy (P = .08). Second primary malignancies excluding nonmelanoma skin cancers were seen in 5.5% and myeloid malignancies/acute leukemia in 1.7%. We observed a favorable efficacy profile of standard-of-care cilta-cel in RRMM, despite more than half the patients not meeting the CARTITUDE-1 eligibility criteria.

Abstract Background: Several immune effector cell (IEC) therapies have been approved for multiple myeloma (MM), including chimeric antigen receptor T-cell (CAR-T) therapies such as idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel). We report 14 cases of IEC-associated enterocolitis, in five cases fatal, following CAR-T therapy in MM. Methods: We performed a retrospective analysis of cases of diarrhea, enterocolitis, or colitis following commercial ide-cel or cilta-cel (including out-of-specification products) at 10 centers within the United States Myeloma Immunotherapy Consortium. Patients were treated according to the local standard of care at each participating center. Results: We identified 14 cases of IEC-associated enterocolitis out of 1159 CAR-T infusions, corresponding to a 1.2% incidence (0.2% for ide-cel and 2.3% for cilta-cel). This proportion excludes 3 cases of potential or confirmed T-cell lymphoproliferative disorders of the bowel. Patients developed acute-onset symptoms (typically non-bloody Grade 3+ diarrhea) with negative infectious workup beginning a median of 79 days (range: 22-210 days) after CAR-T therapy and a median of 74 days after cytokine release syndrome resolution (range: 2-202 days). Biopsies uniformly demonstrated inflammation, with specific findings including intra-epithelial lymphocytosis, crypt dropout on colon biopsies, and villous blunting on duodenal biopsies. Systemic corticosteroids were initiated in 10 patients (71%) a median of 26 days (range: 1-80 days) following symptom onset. Only 40% of steroid-treated patients had symptomatic improvement; subsequent infliximab or vedolizumab led to improvement in 50% and 33% of corticosteroid-refractory patients, respectively. With a median follow-up of 224 days, n = 4 have had diarrhea resolution, n = 5 have had improved or stable symptoms, and n = 5 (36%) have died from IEC-associated enterocolitis or treatment-emergent infections. Conclusions: IEC-associated enterocolitis is a distinct but rare complication of CAR-T therapy characterized by non-bloody diarrhea typically beginning 1-3 months after infusion. Thorough diagnostic workup (including evaluation for potential T-cell malignancies) and appropriate management with an expert gastroenterologist are essential. Further research is critical to understand the pathogenesis of this novel toxicity. In the interim, the early use of infliximab or vedolizumab may potentially hasten symptom resolution and lower reliance on high-dose corticosteroids during the post-CAR-T period.

7508 Background: Idecabtagene vicleucel (Ide-cel) has demonstrated excellent efficacy in patients with relapsed/refractory multiple myeloma (RRMM). However, outcomes in patients with extramedullary disease (EMD) remain to be better characterized. Methods: We included patients from 11 US academic centers, who were evaluated for EMD and were infused with ide-cel between May 2021 and April 2023. Patients with soft tissue or visceral lesions non-contiguous from bony lesions were classified as having true EMD, with paraskeletal disease classified as non-EMD. Disease responses were evaluated using the IMWG criteria. Time-to-event analyses were performed from the date of ide-cel infusion. Results: Among 351 patients with RRMM treated with ide-cel, 84 (24%) had EMD prior to infusion. Median follow-up for the entire cohort was 18.2 months (95% CI: 17-19.3). Baseline characteristics at ide-cel infusion for EMD and non-EMD cohorts are depicted in the table. For the EMD and non-EMD cohorts, the Day 30 objective response rates (ORR) were 58% vs. 69% (p=0.1), Day 30 ≥complete response rates were 16% vs 24% (p=0.11), the Day 90 ORR were 52% vs 82% (p<0.001), and best ORR were 58% vs 82%, respectively. The median progression-free survival (PFS) was 5.3 months (95% CI: 4.1-6.9) for the EMD cohort vs. 11.1 months (95% CI: 9.2-12.6; p<0.0001) for the non-EMD cohort. The median duration of response for EMD among day 30 responders was 6.4 months (95% CI: 5.1-8.4). In a multivariable analysis, EMD was an independent predictor of inferior PFS [hazard ratio 1.8 (95% CI: 1.2-2.5), p<0.001] after adjusting for ECOG status, revised ISS stage, penta-drug refractoriness, elevated ferritin, prior BCMA-directed therapy and use of bridging therapy. Pattern of progression in the EMD cohort (n=68/84) included EMD site only (21%), hematologic only (22%), or both (57%), with comparable PFS for type of progression (p=0.19). The median overall survival (OS) was 14.8 months [95% CI: 9-Not reached (NR)] for EMD and 26.9 months [95% CI: 26.3 vs NR, p=0.006)] for the non-EMD group. Rates of Grade ≥2 cytokine release syndrome or neurotoxicity syndrome were comparable between the two cohorts. Conclusions: Patients with EMD demonstrate significantly inferior Day 90 ORR and presence of EMD is an independent risk factor for inferior PFS. [Table: see text]

Abstract Cytopenias represent the most common side effect of CAR T-cell therapy (CAR-T) and can predispose for severe infectious complications. Current grading systems, such as the Common Terminology Criteria for Adverse Events (CTCAE), neither reflect the unique quality of post–CAR-T neutrophil recovery, nor do they reflect the inherent risk of infections due to protracted neutropenia. For this reason, a novel EHA/EBMT consensus grading was recently developed for Immune Effector Cell-Associated HematoToxicity (ICAHT). In this multicenter, observational study, we applied the grading system to a large real-world cohort of 549 patients treated with BCMA- or CD19-directed CAR-T for refractory B-cell malignancies (112 multiple myeloma [MM], 334 large B-cell lymphoma [LBCL], 103 mantle cell lymphoma [MCL]) and examined the clinical sequelae of severe (≥3°) ICAHT. The ICAHT grading was strongly associated with the cumulative duration of severe neutropenia (r = 0.92, P &lt; .0001), the presence of multilineage cytopenias, and the use of platelet and red blood cell transfusions. We noted an increased rate of severe ICAHT in patients with MCL vs those with LBCL and MM (28% vs 23% vs 15%). Severe ICAHT was associated with a higher rate of severe infections (49% vs 13%, P &lt; .0001), increased nonrelapse mortality (14% vs 4%, P &lt; .0001), and inferior survival outcomes (1-year progression-free survival: 35% vs 51%, 1-year overall survival: 52% vs 73%, both P &lt; .0001). Importantly, the ICAHT grading demonstrated superior capacity to predict severe infections compared with the CTCAE grading (c-index 0.73 vs 0.55, P &lt; .0001 vs nonsignificant). Taken together, these data highlight the clinical relevance of the novel grading system and support the reporting of ICAHT severity in clinical trials evaluating CAR-T therapies.

Abstract In a retrospective analysis at 11 US medical centers, bridging therapy (BT) impact after receiving idecabtagene vicleucel was assessed in 214 patients. 79% received BT, including 12% Selinexor-containing, 45% alkylator-based, 15% proteasome inhibitor combinations, and 18% immunomodulatory drugs +/- monoclonal antibody combinations (IMiD +/- mAb combos). BT recipients had worse performance status, higher stage disease, ferritin and CRP pre-infusion. The overall response rate to BT was 12%, with no difference among BT subgroups. Safety profiles were similar, but Selinexor had a higher grade ≥2 ICANS incidence. Median progression-free survival (PFS) was 6.7 months in BT vs. 11.5 months in no-BT (p=0.007). Median PFS was longest with IMiD +/- mAb combos (12 months), comparable to no-BT, and significantly longer than other BT subgroups (p=0.01). Alkylator-based BT had inferior PFS compared to IMiD +/- mAb combos (p=0.03). Median overall survival (OS) for the BT was 13.8 months vs. not reached in no-BT (p=0.002). Alkylator-based BT had shorter OS compared to others (11.97 months vs. NR; p=0.001). Stepwise Cox regression showed alkylator-based BT and response

Background: The use of CAR-T cell therapy has transformed treatment paradigms in B-cell malignancies. Ciltacabtagene autoleucel (cilta-cel) was approved for use in RRMM after four or more prior lines of therapy in 2022. While the pivotal studies exclusively treated patients in an inpatient setting, robust infrastructure planning at some centers across US has fostered outpatient administration of the commercially available product. Outpatient administration of CAR-T is more desirable due to superior financial sustainability, lower healthcare resource utilization, and greater patient autonomy during the treatment. Hence, we conducted a qualitative study to evaluate clinical and administrative perspectives and trends in outpatient administration of commercialized cilta-cel with an aim to understand best practices from certified CAR-T centers in the USA. Methods: A targeted literature review was conducted to better understand current practices around outpatient administration of CAR-T, and inform the development of primary research materials for designing subsequent interviews. Next, two 60-minute exploratory interviews were conducted with multi-stakeholder participants (n=5) from two certified cilta-cel centers, each with significant volume of outpatient administration of cilta-cel. Following the qualitative analysis of interviews, two 90-minute panels were conducted with multi-stakeholder participants (n=14) from six certified cilta-cel centers, including centers from exploratory interviews, focusing on clinical and administrative topics across the patient journey. Results: Each center in the study treated approximately 15-30 patients with cilta-cel in the outpatient setting. Using Likert scales, participants from all centers ranked space/capacity as the most important factor in decision-making process for outpatient cilta-cel administration, and ranked reimbursement incentives as a highly (67% of participants) or a moderately (33%) important factor. All participants agreed that having a dedicated outpatient infrastructure (dedicated space such as bed availability and internal processes including standard operating procedures (SOPs)), 24/7 support, outpatient bone marrow transplant (BMT) or cell therapy experience, and robust multidisciplinary teams were key to setting-up successful outpatient centers for cilta-cel therapy. The participants agreed that cilta-cel can be administered safely in an outpatient setting due to generally predictable, delayed onset of potential AEs, except in patients with significant comorbidities or organ dysfunction. Participants also considered caregiver support and lodging availability as factors of importance for outpatient administration. Institutionally established AE monitoring protocols are critical for safe use of cilta-cel in an outpatient setting. Over 50% of the centers interviewed have recently started to administer tocilizumab to treat mild grade 1 cytokine release syndrome (CRS) in an outpatient setting. Based on the findings across the phases of research, the patient journey for outpatient administration of cilta-cel was updated (Figure 1). While patients may be admitted for toxicity events, 100% of centers interviewed had 24-hour coverage and bed availability for these patients if needed. Conclusions: Overall, this study further supports the notion that centers can safely administer cilta-cel in an outpatient setting, if appropriate infrastructure is in place. Additional best practices for new outpatient sites include adequate infrastructure, SOPs, a well-trained and multidisciplinary team, and education of patients and caregivers (Table 1). Outpatient management and earlier intervention for low-grade AEs is currently evolving, with more real-world research required. Continued expert sharing of best practices can aid centers in implementing outpatient administration of CAR-T therapies. Funding: This analysis was supported by Janssen Research & Development, LLC and Legend Biotech USA, Inc