Borogovac, Azra

Patients with plasma cell leukemia (PCL) are generally excluded from pivotal T-cell redirecting bispecific antibody (BsAb) trials. We evaluated real-world outcomes in a multicenter retrospective study of 122 patients with primary or secondary PCL across 15 academic centers, categorized as 'active' (≥5% circulating plasma cells within 30 days of BsAb initiation) or 'historical'. In a heavily pretreated population, patients received teclistamab (37%), elranatamab (11%), talquetamab as a line of therapy (Tal LOT, 42%), or talquetamab as bridging therapy to CAR-T (Tal Bridge, 11%). Cytokine release syndrome (CRS) was grade 1-2 in 56% and grade 3-4 in 4%, whereas neurotoxicity was grade 1-2 in 16% and grade 3-4 in 5%. Among 110 evaluable patients, the overall response rate (ORR) was 55%, including 61% with Tal LOT, 58% with Tal Bridge, 46% with elranatamab, and 33% with teclistamab. With a median follow-up of 8.3 months, talquetamab demonstrated superior survival. Tal LOT showed a median progression-free survival (mPFS) of 5.5 months and a median overall survival (mOS) of 11.5 months, and both were unreached in the Tal Bridge cohort. In contrast, teclistamab and elranatamab showed a mPFS of 1.2 and 1.6 months and mOS of 8.1 and 3.6 months, respectively (P=0.007, P=0.023). In active PCL, Tal LOT achieved mPFS/mOS of 6.9/12.2 months versus 0.7/1.4 months with teclistamab and 1.0/3.1 months with elranatamab, respectively (P<0.001, P=0.002). Multivariable analysis associated active PCL with worse survival and Tal LOT with improved outcomes. BsAbs were safe in PCL, with talquetamab showing superior outcomes compared with BCMA-directed BsAbs.

Abstract Background: Dissemination and implementation science (D+I) efforts often begin after clinical trial (CT) efficacy data are available. However, delaying this work limits opportunities to identify barriers and facilitators that can enhance adoption of evidence-based practices. Integrating D+I during trial development, activation, and conduct supports more timely, effective, and scalable implementation. The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) includes >125 centers, conducting transplant and cellular therapy (TCT) trials with practice-changing potential, with >17,000 patients enrolled since 2001. Data from Center for International Blood and Marrow Transplant Research (CIBMTR) provides a way to measure real-world adoption. With this comprehensive structure in place, the BMT CTN launched a D+I Committee that established a D+I process to better understand uptake of CT findings and to leverage that information to promote adoption. Methods: Informed by established D+I frameworks, a structured, cyclical process to integrate implementation considerations spanning the CT lifecycle was developed. A multidisciplinary team including experts in D+I, clinicians, and investigators iteratively refined the proposed D+I algorithm. The process begins upstream when a trial concept is approved to move forward, it is shared with the D+I Committee for initial assessment. This includes a landscape review for studies in development using CIBMTR data, literature, and expert experience. The Committee then reviews the developing protocol with the BMT CTN protocol team to proactively identify implementation barriers and facilitators to implementation in real-world settings and outline plans for dissemination. The Committee also provides recommendations for integrating relevant implementation data collection and analyses within the protocol. After study completion, both clinical efficacy and implementation outcomes are analyzed, followed by active dissemination. Additional assessment using surveys, qualitative methods, and CIBMTR data occurs after dissemination to understand adoption. Insights gathered also inform further refinement of the process. Tools and templates are in development to build capacity and ensure consistency for Committee members. Results: To date, the Committee has published three peer-reviewed articles addressing implementation implications of three BMT CTN trials (PMC7735536, PMC8578257, PMC9364468) and a fourth is in press. Using the designed D+I process flow, a current effort used a survey sent to US CIBMTR centers, to evaluate factors influencing the implementation of results of the BMT CTN 1703 trial of post-transplant cyclophosphamide as graft-versus-host disease (GvHD) prophylaxis and assessed dissemination and adoption considerations for the upcoming BMT CTN 2203 CT of ruxolitinib as GvHD prophylaxis. CIBMTR data is being analyzed to demonstrate practice patterns before, during, and after BMT CTN 1703 study completion. This effort has allowed for further refinement of the BMT CTN D+I process flow and has highlighted critical opportunities for incorporating dissemination and implementation objectives and endpoints into BMT CTN protocols. We also used the process to guide a review of severe aplastic anemia treatment gaps and ongoing studies. This review underscored how proactive transplant and non-transplant stakeholder engagement and early implementation planning, core elements of this process, can bridge evidence to practice and advance access to care. A complementary survey on current practice patterns in severe aplastic anemia is ongoing. Conclusions: With the existing structure of the BMT CTN and associated practice registry of the CIBMTR, the BMT CTN D+I Committee developed a systematic process to build D+I considerations into trial workflows to increase real-world impact. This process aims to ensure that barriers to uptake of trial results can be identified and addressed appropriately, improving care quality for patients undergoing TCT.

Abstract Severe aplastic anemia (SAA) is a rare and life-threatening bone marrow failure disorder. Immunosuppressive therapy (IST) with antithymocyte globulin and cyclosporine has long been a frontline treatment option in SAA; however, its limited durability and risk of long-term complications such as secondary malignancies remain a drawback in this treatment modality. Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative option with significantly improved outcomes over the long term, particularly with HLA-matched related donors. However, the use of alternative donors, such as haploidentical, mismatched, or matched unrelated donors, has previously been limited due to increased transplant-related morbidity, particularly graft-versus-host disease (GVHD). HCTs have therefore been limited to young recipients and those with HLA-matched related donors, creating significant disparity for older adults and those who lack matched donor options. Nevertheless, more recent advances in HCT, such as posttransplant cyclophosphamide for GVHD prophylaxis, have led to improved outcomes of HCT with alternative donors; however, alternative donor HCT remains underused as up-front therapy, in part because of limited multicenter trial data. This review discusses current SAA treatment approaches, including both IST and HCT, and highlights remaining gaps. It also discusses how ongoing clinical trials such as CureAA and TransIT could help address these gaps. Furthermore, we discuss the importance of stakeholder engagement and implementation science in the integration of research-based evidence into clinical practice. Bridging these gaps is necessary for achieving equitable access for patients historically excluded from frontline HCT, including older adults and racially or ethnically diverse populations.

7514 Background: The AETHERA trial demonstrated improvement in PFS with 16 cycles of brentuximab vedotin (BV) after autologous stem cell transplant (ASCT) in BV-naive patients with high-risk relapsed/refractory classical Hodgkin lymphoma (r/r cHL). However, in real world, patients are rarely able to complete all 16 cycles of BV at full dose. We performed a multicenter retrospective study to assess the impact of cumulative dose on toxicity and 2-year PFS. Methods: Patients from 11 institutions across the US who had received at least one cycle of BV maintenance after ASCT for r/r cHL with one of these features were included: primary refractory disease (PRD), extra-nodal disease (END), or relapse < 12 months of diagnosis (RL<12). PFS was compared between the three cohorts based on a total cumulative dose of 28.8 mg/kg (1.8 mg/kg x 16 cycles): C1, those that received >75% (21.7 to 28.8 mg/kg) cumulative dose of BV, C2, those that received between 51% -75% (14.5 to 21.6 mg/kg) dose and C3, those that received ≤ 50% (≤ 14.4 mg/kg) dose. Results: Between July 2015-June 2019, 100 patients with a median age of 34 years (19-70) underwent ASCT for r/r cHL. At relapse, 44% had PRD, 47% had RL<12, 39% had END and 45% had received BV as initial (1%) or salvage (44%) therapy. 71% had CR before ASCT and 23% received >1 line of salvage (>1 SLT). There was no difference in baseline characteristics between the cohorts. Thirty-six patients were in C1, 27 in C2, and 37 in C3. Only 14% of patients received full cumulative dose of BV. The median number of cycles completed was 12. Fifty-seven patients discontinued early: 39 for toxicity, 7 for progression, 5 for patient preference, 2 for cost and 4 for other reasons. Six of the patients who stopped early for progression were in C3. Grade ≥3 adverse events for neuropathy, neutropenia, and infections were 16%, 7%, and 5% respectively. There was no difference in severity of neuropathy in patients who had received BV prior to ASCT (p=.37). The median follow up was 3.37 years (.4–6.35). The 2-year PFS was 85% for all subjects, 94% for C1, 84% for C2, and 72% for C3 (p=.079) (Table). Patients in C3 had worse PFS compared to C1 (p=.035); this difference remained significant after adjusting for five other factors. There was no difference in PFS between C1 and C2 (p=.29). Conclusions: The majority of patients discontinued BV maintenance early due to toxicity. 2-year PFS was robust regardless of cumulative dose of BV. We conclude that total cumulative dose of 28.8 mg/kg of BV maintenance is not necessary and 51%-75% of total BV dose may still attain a similar PFS advantage. [Table: see text]