Citations

Purpose Outcomes with bispecific T-cell engagers (TCEs) in relapsed/refractory multiple myeloma (RRMM) are heterogeneous. A practical tool to guide prognosis is needed. We developed a model integrating clinical, biological, and treatment-related variables to predict progression-free survival (PFS) in patients receiving B-cell maturation antigen (BCMA)- or G-protein–coupled receptor class 5 member D-directed TCEs. Methods We evaluated outcomes of 577 BCMA-directed and 366 talquetamab treatments across 15 US Multiple Myeloma Immunotherapy Consortium centers. Variables significantly associated with inferior PFS in a multivariate Cox model were incorporated into a prognostic score and validated in an independent multicenter International Myeloma Foundation cohort. Results With a median follow-up of 8.4 months, the median PFS was 6.4 months (7.0 months for BCMA TCE; 6.1 months for talquetamab); 92% of patients were triple-class-refractory. Six variables significantly associated with inferior PFS—high-risk cytogenetic abnormalities (HRCAs) [del(17p) or ≥2 HRCAs], hyperferritinemia (≥600 ng/mL), anemia (hemoglobin <9 g/dL), early relapse (<18 months from frontline therapy), general performance status (Eastern Cooperative Oncology Group Performance Status ≥2), and exposure to prior BCMA-directed therapy—were combined to form the CHARGE index, stratifying patients into three risk groups. The median PFS was 21.8 months (95% CI, 11.7 to not reached), 7.1 months (95% CI, 6.1 to 10.1), and 1.6 months (95% CI, 1.2 to 2.5) in the low-, intermediate-, and high-risk groups, respectively; hazard ratios (HRs) were 2.0 (95% CI, 1.5 to 2.7) and 4.8 (95% CI, 3.5 to 6.7) for intermediate- and high-risk versus low-risk groups. External validation (n = 173) showed that the median PFS was not reached, 7.0 months, and 3.0 months, with corresponding HRs of 2.9 (95% CI, 1.7 to 4.9) and 4.8 (95% CI, 2.6 to 8.7). Conclusion The CHARGE index provides a simplified and externally validated framework for predicting treatment outcomes in patients with RRMM receiving TCEs.

Cardiac allograft vasculopathy (CAV) remains a leading cause of graft failure after heart transplantation, yet an early, non-invasive risk stratification tool is not available. Artificial intelligence electrocardiography (AI-ECG) can estimate biological heart age, and it has been associated with cardiovascular risk. Its deviation with chronological age, called delta age, and its utility in the prediction of CAV has never been explored. We conducted a retrospective single-center study for heart transplant recipients bridged with Impella 5.5 (Abiomed, Danvers, MA, USA) at Mayo Clinic Florida (2020–2023). ΔAge was calculated at discharge and 1-year post-transplant. The primary outcome was confirmed CAV at 1 year. Univariate and multivariable logistic regression models were used to assess the independent association between the ΔAge and the development of CAV, with discrimination evaluated by AUC and internally validated via bootstrap resampling (2000 iterations). Fifty patients were reviewed. CAV developed in 13 (26%) patients in 3 years. CAV+ patients had a significantly higher ΔAge at discharge compared to CAV- patients (median −1.0 vs. −11.0 years, p = 0.0023) and at 1 year (median +7.0 vs. −4.0 years, p = 0.0080). On univariate analysis, ΔAge at discharge was a significant predictor of the development of CAV (OR 1.084 per year, AUC 0.788). On multivariable adjustment, ΔAge at discharge remained an independent predictor (adjusted OR 1.138, 95% CI 1.023–1.265, p = 0.018, and model AUC 0.859). ΔAge at discharge is a novel and potential predictor of the development of CAV within 3 years. These findings support the integration of AI-ECG into post-transplant surveillance as a scalable, low-cost tool.

Background: Since publication of the American Society of Hematology 2019 Guidelines for Immune Thrombocytopenia (ITP), new clinical trials have been completed and new treatments have become available. Objective: These evidence-based guidelines from the American Society of Hematology (ASH) are a focused update of the 2019 ASH ITP guidelines, centering on treatment of adults with primary ITP. Methods: ASH formed a multidisciplinary guideline panel including two patient representatives that was balanced to minimize potential bias from conflicts of interest. The University of Oklahoma supported the guideline development process, including updating or performing systematic evidence reviews (up to July 19, 2025). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients and identification of areas with new data or where application of new methods would be of benefit. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE Evidence-to-Decision frameworks and the GRADE framework for multiple comparisons, to assess evidence and make recommendations, which were subject to public comment. Results: The panel agreed on recommendations in adults with primary ITP regarding initial therapy and second-line treatment in patients who failed first-line corticosteroids. The panel also issued good practice statements on thrombopoietic agent switching and splenectomy. Conclusions: Novel recommendations of these guidelines include: (1) initial therapy with a combination of rituximab plus corticosteroids or a thrombopoietic agent plus corticosteroids rather than corticosteroids alone (conditional recommendation) and (2) a thrombopoietic agent (strong recommendation) or rituximab (conditional recommendation) for patients who failed first-line corticosteroids.

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&lt;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.

Post-transplant lymphoproliferative disorder (PTLD) involving the central nervous system (CNS) is a rare but serious life-threatening complication seen in recipients of solid organ transplant. Primary CNS encompasses 5–15% of all types of PTLD diagnoses, and heart transplant recipients represent 3–5% of those reported cases. Diagnosis is often delayed due to the highly variable presentation, with some cases remaining undiagnosed for years. Multidisciplinary collaboration is crucial for early diagnosis and management. A 53-year-old woman patient presented with altered mental status. MRI revealed nodular ventriculitis and bilateral periventricular hyperdense infiltrates. CSF studies demonstrated lymphocytic pleocytosis, elevated protein, and EBV-PCR-positive results. A stereotactic brain needle biopsy confirmed the presence of EBV-positive diffuse large B-cell lymphoma, consistent with primary CNS PTLD, 14 months after her heart transplant. Despite appropriate management, the patient experienced progressive neurological decline and ultimately suffered a fatal intracerebral hemorrhage. We demonstrate the importance of the early diagnosis and variable presentation of post-heart-transplant PTLD. The importance of surveillance regardless of EBV status and close monitoring of disease progression due to potential life-threatening complications, such as fatal hemorrhages. Therefore, primary CNS-PTLD remains a challenging disease and is being increasingly recognized with improved transplant recipient survival and prolonged exposure to chronic immunosuppression.

Abstract Idecabtagene vicleucel (ide-cel) is a chimeric antigen receptor (CAR) T-cell therapy approved for relapsed and refractory multiple myeloma (RRMM). Out-of-specification (OOS) CAR T cells not meeting criteria for commercial release are considered an investigational product; the expanded access protocol (EAP) allows release of OOS product for administration. The manufacturing analysis of capability, reliability, and timely delivery of ide-cel in the United States over &gt;3 years since its approval included patients with RRMM who underwent leukapheresis for ide-cel treatment after ≥2 prior lines of therapy between 23 February 2021 and 1 November 2024. Additionally, the BB2121-EAP-001 study evaluated safety and efficacy of OOS ide-cel and included patients who had undergone leukapheresis for commercial ide-cel treatment not meeting commercial release specifications, most commonly due to high CD137 activation or low-infused dose. Primary end point was safety. Secondary end points were overall response rate (ORR) and complete response rate (CRR). At data cutoff (1 November 2024), the manufacturing success rate of ide-cel improved from 95.3% in 2021 to 96.8% in 2024. Turnaround time also improved from 31 days in 2021 to 24 days in 2024. In BB2121-EAP-001, 68 (72.3%) patients experienced ≥1 cytokine release syndrome event (mostly grade 1/2) and 15 (16.0%) had neurological toxicities (2 grade 3, 13 grade 1/2). ORR was 75.4% (95% confidence interval [CI], 63.1-85.2), and CRR was 35.4% (95% CI, 23.9-48.2). The manufacturing success of ide-cel is reliable and consistently high, and when OOS ide-cel products emerged, they demonstrated consistent clinical efficacy and safety. The BB2121-EAP-001 study was registered at www.clinicaltrials.gov as NCT04771078.