Use of anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) therapy to treat relapsed/refractory multiple myeloma is increasing. Studies suggest that effective bridging therapy (BT) prior to anti-BCMA CAR-T therapy can enhance efficacy and safety outcomes. Through qualitative interviews and a consensus workshop, 10 European experts shared their clinical experience regarding optimal BT selection, efficacy, safety and outcomes post-CAR-T, focussing on heavily pretreated patients and emerging BT options, such as bispecific T-cell engagers. Experts agreed that BT should aim to reduce tumour burden and maintain or improve patient performance status, while avoiding treatment-related toxicity that could delay or prevent CAR-T infusion. The balance between treatment duration and achieving an adequate response is important, and patient characteristics are key for BT selection, especially in difficult-to-treat populations. Here, we discuss the unique therapy talquetamab, a GPRC5DxCD3 bispecific antibody, which demonstrates robust efficacy and rapid response rates in clinical trials, and is being considered as a BT option before anti-BCMA CAR-T therapy based on expert experience and real-world data. This consensus, based on clinical experience, aims to provide guidance on BT for healthcare professionals (HCPs) involved in anti-BCMA CAR-T therapy and aid standardisation of care in this rapidly advancing field.

This was the first study to assess patient-reported outcome (PRO) trajectories among patients with relapsed/refractory multiple myeloma (RRMM) receiving standard of care chimeric antigen receptor T-cell therapy (CAR-T) and to compare PRO trajectories by treatment group, idecabtagene vicleucel (ide-cel) vs. ciltacabtagene autoleucel (cilta-cel). Participants completed health-related quality of life (HRQOL) and symptom surveys at enrollment/baseline (pre-lymphodepletion), infusion day(D)0, D7, D14, D21, D30, D60, and D90. Piecewise growth curve models assessed PRO trajectories pre-D7 and post-D7. Among 99 participants, ide-cel recipients (n = 49) were older than cilta-cel recipients (n = 50) (median 73 vs. 64 years, p < 0.001). Many PROs worsened pre-D7 and improved post-D7, including overall HRQOL, physical well-being, functional well-being, fatigue, physical function, and social function (p-values < 0.05). Several PROs were stable pre-D7 and improved post-D7, including anxiety, sleep disturbance, pain interference, and pain intensity (p-values < 0.05). There were differences between groups in the trajectories of social well-being pre-D7 (p = 0.01) and cognitive function post-D7 (p = 0.001). Patients with RRMM receiving standard of care CAR-T had similar PRO trajectories regardless of CAR-T type, with most PROs initially worsening or stable before significantly improving post-treatment. Future studies should investigate potential differences by treatment for social well-being and cognitive function as well as PRO trajectories beyond D90 post-treatment.

CHRONOS is a multicenter, retrospective, cohort study involving acute graft-versus-host disease (aGvHD) adult patients with gastrointestinal (GI) symptoms, steroid- and ruxolitinib refractory, who initiated third-line therapy between 30 May 2019 and 30 September 2024. Primary endpoints were all-organ overall response rate (ORR) and GI-specific ORR (GI-ORR) around 28 days after treatment initiation. Secondary endpoints included duration of response, real-world progression-free survival (rwPFS) of underlying malignancy, and overall survival (OS). Fifty-nine patients from 16 sites in Europe were included. On Day 28, ORR was 36% (95% CI: 24-49%), GI-ORR was 37% (95% CI: 25-51%); 29% (95% CI: 11-49%) of responders lost response within 30 days, and 52% (95% CI: 29-72%) within 90 days. Median rwPFS and median OS were both 86 days (95% CI: 54-128 days). Median OS was higher in responders than in non-responders (186 versus 45 days). Over the 12-month follow-up period, 41 patients died, mainly due to aGvHD progression (n = 25), and infectious complications (n = 9). Within 3 months, Grade ≥ 2 infectious events occurred in 51% of patients; Grade 3-4 thrombocytopenia and neutropenia in 64% and 32%, respectively. These findings demonstrate limited effectiveness of third-line therapy in this cohort of steroid- and ruxolitinib-refractory aGvHD patients with GI symptoms.

Haploidentical hematopoietic stem cell transplant (Haplo-HSCT) has emerged as an alternative for patients lacking matched human leukocyte antigen (HLA) donors. The scarcity of stem cell donor registries and cord banks across the Eastern Mediterranean (EM) region has led to increased need of Haplo-HSCT as a mean to overcome this limitation. In this study, we aimed to assess trends in Haplo-HSCT utilization within the Eastern Mediterranean Blood and Marrow Transplantation (EMBMT) registry from 2012 to 2024, and describe key clinical and transplant-related factors associated with patient outcomes. We conducted a retrospective, multicenter registry-based analysis of patients who had their first un-manipulated Haplo-HSCT in ten EMBMT centers across six countries, who responded and accepted to participate in the study. Due to the variability in time-to-event reporting across different centers, survival and relapse-related outcomes were analyzed descriptively. Continuous variables were summarized using medians and ranges, and categorical variables were described by counts and percentages. The association between individual baseline variables and patient survival, was conducted using a univariate analysis utilizing the chi-square test. Categorical variables such as patient and transplant characteristics were compared against survival status at last follow-up. All variables were further evaluated in the multivariate analysis. Overall survival (OS) and progression-free survival (PFS) were estimated using Kaplan-Meier survival analysis. Between 2012 and 2024, a total of 673 patients received haplo-HSCT across ten centers, in six EMBMT-registered countries. Median age was 25 years, and the predominant indication for haplo-HSCT was leukemia (64.3%). Transplant was done using stem cells collected from peripheral blood in majority of cases (65.7%), and Total Body Irradiation (TBI) was utilized in 37.6% of all patient. 76.5% had malignant hematological disorders, while 23.5% had non-malignant disorders. Relapse was reported in 232 patients (34.5%) and death in 220 patients (32.7%). Of these, 88 deaths (12.8%) were attributed to disease progression. Haplo-HSCT activity increased steadily over the study period, with a marked increase in the last few years, reflecting broader regional adoption. PFS was 66% and 60% at 1- and 2- years after transplantation. Also, the 1-year and 2-year post-transplant OS was 71% and 65%, respectively. Multivariate analysis identified disease type and chronic GVHD as factors associated with improved outcomes. Despite variability across centers, outcomes were consistent with international benchmarks, underscoring the growing feasibility and therapeutic value of haplo-HSCT in the EMRO region. Haplo-HSCT is increasingly adopted across the EMRO region as the primary alternative donor HSCT modality. Our findings confirm its clinical efficacy, with outcomes comparable to international benchmarks. These results underscore the importance of continued regional collaboration and the development of personalized strategies to address challenges such as graft-versus-host disease (GVHD), disease relapse, and disparities in access to transplantation services.

Myelodysplastic/myeloproliferative neoplasms (excluding CMML) are rare and heterogenous malignancies with recurrent and overlapping clinicopathological abnormalities. Classification and characterization continue to evolve, but outcomes remain unsatisfactory and allo-HCT is currently the only curative therapy. Experience with these diseases is limited by rarity, accounting for <1% of allo-HCT procedures in Europe annually. Transplant indications have recently been described by this group, however response assessment, post-transplant surveillance and management of poor graft function, splenomegaly and relapse are not well established. To address this gap, the European Society for Blood and Marrow Transplantation (EBMT) Practice Harmonization & Guidelines (PH&G) Committee and the Chronic Malignancies Working Party (CMWP) collaborated to develop a practical and expert consensus-based guideline. Criteria for remission confirmation are proposed, including timing/thresholds for morphological, molecular, cytogenetic and chimerism analysis, aiming to harmonize comparisons in registry data and between international series. Suggestions for managing poor graft function and splenomegaly are designed to broadly align with those for myelofibrosis and related disorders. Relapse post-transplant remains a frequent challenge and the lack of robust evidence, in both the pre-transplant/post-transplant setting, underpins a need for collaborative clinical trials. This document serves as a framework to model post-transplant care, guide future research and address unresolved questions.