Lodowski, Nicole

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

Introduction Relapsed/refractory multiple myeloma (RRMM) is a hematologic cancer associated with no current widely-accepted cure, cycles of relapse and remission, treatment resistance, and high morbidity and mortality, which necessitate new treatments and therapeutic targets. 1-3 Innovative therapies that target BCMA, CD38, GPRC5D, FcRH5, and others in the RRMM development pipeline are recently approved or under investigation, but real-world evidence on clinician perceptions of emerging trends and unmet needs remains limited. A Delphi panel was conducted with US clinicians to evaluate the level of unmet need and treatment decisions among patients with RRMM who are triple-class-exposed (TCE). Methods This double-blinded study consisted of two phases: a web survey (phase 1) and a Delphi panel (phase 2). A targeted literature review was conducted first to understand unmet needs and treatment decisions associated with management of RRMM in the US and inform the development of primary research materials. The web survey was completed by 21 US clinicians. Survey findings were then used to inform the phase 2 Delphi panel, a systematic, validated approach to gain consensus. This consisted of two iterative rounds of a question answered by nine experts selected from participants in the web survey. Consensus on a question was defined as at least 70% agreement. The double-blinded panel was conducted via the Microsoft Teams platform, and poll questions were administered through Vevox. Responses were blinded to preserve respondents' anonymity and participants were also blinded to the study sponsor. Results Overall, consensus was reached that despite recent improvement in treatment landscape, there is still a high level of unmet need for patients with RRMM who are TCE (89% of participants). More specifically, consensus was reached (89%) that the top three areas of unmet need were treatment resistance, guidance on treatment sequencing, and novel mechanisms of action (MoAs) and targets (Figure 1). Unmet need is also particularly pronounced for certain patient subgroups, with 89% and 78% of participants agreeing that patients who are functionally high-risk and penta-refractory, respectively, experience the greatest unmet need. When asked about which novel therapies would be most promising for addressing the unmet needs, participants agreed that the top 4 therapeutic targets are GPCR5D (95%), BCMA (81%), FcRH5 (81%), and BCL-2 (81%). Various factors impact treatment choice and sequencing, with most participants (78%) agreeing that treatment history is the most influential factor impacting sequencing. The panel also agreed that prior toxicity (grade 3-4 AEs, 89%) and convenience of dosing frequency (78%), respectively, most impact dosing decisions. All agreed there is a need for resources to manage some AEs, particularly newer AEs (like skin and nail effects) of emerging treatments. Of the AEs identified in the survey as top drivers of treatment choice, participants reached consensus on two: neurotoxicity (e.g., ICANS) (89%) and infection (100%). Conclusions In this Delphi study, consensus was reached that a high level of unmet need remains for patients with RRMM, who are TCE with unmet need varying dependent on patient subgroup and treatment history. There was consensus that additional treatment choices with novel targets/MoAs are needed. Participants agreed that AEs, toxicity, infection, and treatment history impact treatment choice and sequencing, and considerations and challenges vary by subgroup. Overall, findings from this study support that there is a need for additional treatment options with novel MoAs/therapeutic targets that address priority unmet needs for patients with RRMM, who are TCE. References 1. Gonsalves W et al. The next generation of novel therapies for the management of relapsed multiple myeloma. Future Oncol (London, England). 2017;13(1):63-75. https://doi.org/10.2217/fon-2016-0200 2. Braunstein M et al. A new decade: novel immunotherapies on the horizon for relapsed/refractory multiple myeloma. Expert Rev Hematol. 2022;14(4):377-389. doi:10.1080/17474086.2021.1909469 3. Bruno AS et al. Recent real-world treatment patterns and outcomes in US patients with relapsed/refractory multiple myeloma. Expert Rev Hematol. 2020;13(9):1017-1025. doi:10.1080/17474086.2020.1800451