Tidswell R, Owen C, Shafey M
… +5 more, Perry S, Cox-Kennett N, Sterrett R, Peters A, Puckrin R
Eur J Haematol
· 2026 Jun · PMID 41698679
·
Full text
INTRODUCTION: Novel targeted agents have transformed the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), including continuous BTK inhibitor (BTKi) therapy and time-limited regimens such as...INTRODUCTION: Novel targeted agents have transformed the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), including continuous BTK inhibitor (BTKi) therapy and time-limited regimens such as venetoclax-obinutuzumab (Ven-O) and ibrutinib-venetoclax (I + V). However, factors guiding first-line treatment decisions in routine practice remain poorly defined. OBJECTIVES: To describe real-world first-line treatment patterns and identify factors associated with therapy selection. METHODS: This retrospective, population-based study included consecutive patients initiating first-line therapy for CLL/SLL in 2024 in Alberta, Canada. RESULTS: Among 148 patients with median age 71 years, time-limited targeted therapy was selected for 75 (51%), including Ven-O (n = 73) and I + V (n = 2). Continuous BTKi therapy was used in 65 (44%), while chemotherapy-based regimens were uncommon (n = 8, 5%). Among 138 patients treated with either continuous BTKi or Ven-O, BTKi use was significantly more frequent among those with del(17p)/TP53 mutation (84% vs. 16%, p = 0.0002), age > 75 years (66% vs. 34%, p = 0.0051), and residence > 100 km from an obinutuzumab-initiating cancer center (70% vs. 30%, p = 0.031). CONCLUSIONS: Time-limited and continuous targeted therapies are used with similar frequency for CLL/SLL, with selection shaped by age, TP53 aberrations, geography, and patient preferences. These findings highlight the importance of personalized care and the need to reduce access barriers to time-limited strategies.
Choon-Quinones M, Obeng GD, Asiedu-Ayeh B
… +10 more, Kawuo S, Tukur AM, Mohammed I, Obeng AP, Harousseau JL, Seckinger A, Hose D, Sarkodie E, Imre A, Csanádi M
Eur J Haematol
· 2026 Jun · PMID 41692035
·
Full text
Minimal residual disease (MRD) is a central biomarker in multiple myeloma (MM), offering unprecedented sensitivity for evaluating treatment efficacy and serving as a potential surrogate endpoint. We conducted a comprehen...Minimal residual disease (MRD) is a central biomarker in multiple myeloma (MM), offering unprecedented sensitivity for evaluating treatment efficacy and serving as a potential surrogate endpoint. We conducted a comprehensive analysis of clinical trials registered on ClinicalTrials.gov between 2014 and 2025. Interventional trials or observational studies investigating therapeutic interventions were included. Data on therapy response, MRD outcomes, measurement, and their role as primary, secondary, or adaptive endpoints were extracted. A total of 1336 studies met inclusion criteria. Among interventional trials, 86.4% included therapy response and 30.9% MRD as an outcome. Trials assessing MRD increased steadily from 6.7% in 2014 to 56.8% in 2025. Almost 50% of trials with recruiting (46.0%) or not yet recruiting (46.8%) status had an MRD outcome. MRD served as a primary outcome in 28.4% of trials with MRD assessment and guided therapeutic decisions in 7.5%. Most studies used next-generation flow or sequencing at a 10 threshold, though reporting heterogeneity persisted. MRD integration in trials has expanded substantially, reflecting its clinical and regulatory importance. Still, there is a need for coordinated evidence generation, standardization, and alignment with evolving EMA and HTA requirements. Future research should integrate patient experience data and emerging non-invasive MRD technologies to enhance clinical relevance and policy acceptance.
Khatib H, Parizat A, Halloun J
… +21 more, Shouval R, Shibli N, Alalouf O, Zuckerman T, Halamish I, Sapir D, Yehudai-Ofir D, Ringelstein-Harlev S, Horowitz NA, Lavi N, Horesh N, Fineman R, Tzoran I, Levi T, Dann EJ, Mruwat A, Brenner B, Hoffman R, Rozenberg A, Shechtman Y, Beyar-Katz O
CAR-T cell therapy is efficient in relapsed/refractory B-cell lymphoma; yet, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) remain major and potentially life-threatenin...CAR-T cell therapy is efficient in relapsed/refractory B-cell lymphoma; yet, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) remain major and potentially life-threatening complications, which makes their prediction and prevention crucial. This international, retrospective study analyzed the predictive value of coagulation parameter dynamics for ICANS and CRS development in 265 B-cell lymphoma patients at two tertiary-care centers. Platelet counts, fibrinogen, PT, PTT, international normalized ratio, and D-dimer, were recorded daily from pre-lymphodepletion through 2 weeks post-infusion. ICANS occurred in 34% of patients, with high-grade events documented in 13%. Patients with ICANS had significantly lower median platelet (67 vs. 123 × 10/μL) and fibrinogen (263 vs. 379 mg/dL) levels than those without ICANS. During high-grade ICANS days, fibrinogen and platelet levels were significantly reduced (p = 0.003 and p = 1.6 × 10, respectively). In > 75% of high-grade ICANS cases, 1 day before its onset, platelet counts were < 100 × 10/L (median decrease: 11.6% versus 1.6% on other days; p = 0.001). Conversely, on the day preceding ICANS onset, higher fibrinogen concentrations were observed, with median values of 448 mg/dL in the ICANS group versus 376 mg/dL in the non-ICANS group (p = 0.03). These findings suggest that platelet and fibrinogen dynamics could be early indicators of ICANS development in lymphoma patients.
The prognostic value of bone marrow plasma cell percentage (BMPC%) in systemic light-chain (AL) amyloidosis remains controversial. This meta-analysis aimed to determine the association between BMPC% ≥ 10% and survival ou...The prognostic value of bone marrow plasma cell percentage (BMPC%) in systemic light-chain (AL) amyloidosis remains controversial. This meta-analysis aimed to determine the association between BMPC% ≥ 10% and survival outcomes in patients with AL amyloidosis. We systematically searched multiple databases for studies published through September 2025. Ten studies involving 5322 patients were included. A BMPC% ≥ 10% was significantly associated with poorer OS (pooled HR = 1.35, 95% CI [1.13, 1.62], p = 0.001) and PFS (pooled HR = 1.63, 95% CI [1.29, 2.04], p < 0.001). Consistently, patients with BMPC% ≥10% had significantly shorter mean OS (MD = -31.79 months, 95% CI [-43.22, -20.36], p < 0.0001) and mean PFS (MD = -16.12 months, 95% CI [-40.69, -1.54], p < 0.0001). Significant heterogeneity was observed, for which study design was identified as a major source. Evidence of publication bias was present. This meta-analysis provides robust evidence that a BMPC% ≥ 10% is an independent predictor of inferior OS and PFS in AL amyloidosis. Integrating this readily available biomarker with existing cardiac-based staging systems could enhance risk stratification and inform clinical decision-making.
Robinson R, Berger T, Shochat T
… +13 more, Aumann S, Nachmias B, Goldschmidt N, Horesh N, Harel R, Aviv A, Shimony S, Goldberg I, Shmerts E, Abadi U, Raanani P, Gafter-Gvili A, Gurion R
BACKGROUND: The GALLIUM trial showed improved progression-free survival (PFS) with obinutuzumab (O)-based chemoimmunotherapy in first-line treatment of follicular lymphoma (FL), although with increased toxicity compared...BACKGROUND: The GALLIUM trial showed improved progression-free survival (PFS) with obinutuzumab (O)-based chemoimmunotherapy in first-line treatment of follicular lymphoma (FL), although with increased toxicity compared to rituximab (R). Our previous real-world study found similar toxicity between these protocols during induction. AIM: To compare real-world toxicity and outcomes of R versus O maintenance therapy in FL patients following first-line chemoimmunotherapy. METHODS: A multicenter retrospective study included FL patients treated with first-line R- or O-based chemoimmunotherapy. The primary outcome was any infection up to 6 months post-maintenance. Secondary outcomes included other toxicities, PFS, and overall survival (OS). RESULTS: We analyzed 134 patients (R: 71, O: 63). Baseline characteristics were similar except for higher diabetes and hypertension rates in the R group. The median number of maintenance cycles was comparable. Infections occurred in 56% of patients, with no significant difference (50.7% R vs. 61.9% O, p = 0.21). Grade 3 infections, febrile neutropenia, and treatment discontinuation rates were comparable between groups. Pneumonia and viral infections were less frequent with R versus O (13.8% vs. 28.1%, p = 0.019 and 19% vs. 39%, p = 0.004, respectively), while infusion reactions were higher (8.4% vs. 0%, p = 0.028). After 5.5 years, PFS favored O (19.7% vs. 4.8%, p = 0.028), with similar OS. CONCLUSIONS: In real-world settings, rituximab- and obinutuzumab-based chemoimmunotherapy with maintenance for FL exhibited a similar toxicity profile, with differences in specific infections. Obinutuzumab had superior PFS and similar OS compared with rituximab therapy, supporting obinutuzumab usage in first-line chemoimmunotherapy, especially in selected young and fit patients.
Anemia frequently complicates cancer care, leading to reduced quality of life and poorer overall prognosis. Even mild-to-moderate anemia in cancer patients has been associated with worse outcomes, including increased fat...Anemia frequently complicates cancer care, leading to reduced quality of life and poorer overall prognosis. Even mild-to-moderate anemia in cancer patients has been associated with worse outcomes, including increased fatigue, physical decline, and decreased tolerance to cancer therapies. Importantly, studies have demonstrated that correcting anemia and improving hemoglobin levels can significantly alleviate fatigue, enhance emotional well-being, and improve overall quality of life. An improved understanding of the underlying mechanisms of cancer-related anemia has led to the development of a range of therapeutic strategies, from traditional supportive measures to innovative targeted therapies. In the following manuscript, we provide an in-depth review of these approaches, beginning with established treatments and progressing to newer investigational therapies and specialized strategies for patients with solid tumors and hematologic malignancies. This framework aims to guide clinicians in selecting and tailoring anemia management to improve outcomes and quality of life for patients across cancer types.
Hidalgo-Soto M, Rodríguez-Lobato LG, Motlló Borrella C
… +16 more, Sánchez Cayuela Á, Lopez Pardo J, Rosiñol L, Cibeira MT, García-Guiñon A, Tolosa-Ridao C, Carro Arostegui I, Sureda A, Herranz MJ, Abella Montreal E, Pelicano M, Barrau Alzuria Y, Cortes Sansa M, Gironella M, González Y, Fernández De Larrea C
Double- and triple-refractory multiple myeloma (RRMM) still represents a considerable clinical challenge. Pomalidomide, cyclophosphamide and dexamethasone (PCd) remain a valid treatment option in this setting. This retro...Double- and triple-refractory multiple myeloma (RRMM) still represents a considerable clinical challenge. Pomalidomide, cyclophosphamide and dexamethasone (PCd) remain a valid treatment option in this setting. This retrospective, multicentric study evaluated the activity and safety of PCd in patients with RRMM treated following standard clinical practice. A total of 179 patients were included. The median age was 72 years; most were triple-refractory (59.8%), being 162 patients (90.5%) refractory to lenalidomide and 117 (65.4%) to anti-CD38. The overall response rate (ORR) was 59.8% (95% CI: 52.2-67.0). Triple-refractory patients had an ORR of 52.3% (95% CI: 42.5-62.1). The median progression-free survival (PFS) and overall survival (OS) were 7.9 months (95% CI: 6.8-10.1) and 16.1 months (95% CI: 12.8-20.5), respectively. Patients refractory to lenalidomide and anti-CD38 had a median PFS of 7.6 months (95% CI: 5.8-9.4) and 7.6 months (95% CI: 5.8-9.4), respectively. Most frequent grade 3-4 adverse events were neutropenia (57.5%), anaemia (30.7%) and thrombocytopenia (29.6%). PCd demonstrated effectiveness in double- and triple-refractory RRMM patients, including those refractory to anti-CD38 and is a viable treatment option for these patients.
Alvaro ME, Martino EA, Caserta S
… +10 more, Skafi M, Bruzzese A, Amodio N, Lucia E, Olivito V, Labanca C, Mendicino F, Vigna E, Morabito F, Gentile M
Eur J Haematol
· 2026 Jun · PMID 41651798
·
Full text
Multiple myeloma (MM) remains an incurable plasma cell malignancy characterized by recurrent relapses and eventual refractoriness to standard agents, including proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs),...Multiple myeloma (MM) remains an incurable plasma cell malignancy characterized by recurrent relapses and eventual refractoriness to standard agents, including proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and anti-CD38 monoclonal antibodies. With frontline therapeutic strategies increasingly employing quadruplet induction regimens and prolonged lenalidomide maintenance, resistance to traditional IMiDs has become more prevalent, creating an urgent need for next-generation cereblon E3 ligase modulators (CELMoDs) capable of overcoming IMiD refractoriness and enhancing the immunologic microenvironment. Iberdomide (CC-220) and mezigdomide (CC-92480) are rationally engineered CELMoDs designed to achieve deeper degradation of Ikaros (IKZF1) and Aiolos (IKZF3), restore cereblon-mediated activity, and potentiate immune effector responses. This review explores the core biological features of these agents, detailing their mechanisms of action, preclinical and clinical activity, as well as safety profile. We examine how their pharmacodynamic properties differ from classical IMiDs, their relevance in triple-class and penta-refractory MM, and their integration into emerging combination strategies with monoclonal antibodies and T-cell-redirecting immunotherapies. Special emphasis is placed on ongoing and future trials that may refine their therapeutic positioning, alongside a critical appraisal of the limitations and future directions of this rapidly advancing drug class.
Thieblemont C, Colrat F, Sellami R
… +4 more, Sivignon M, Petel A, Branchoux S, de Pouvourville G
Eur J Haematol
· 2026 Jun · PMID 41651792
·
Full text
OBJECTIVES: CAR-T cell therapies such as lisocabtagene maraleucel (liso-cel) have transformed the treatment of patients with second line primary refractory or early relapsed ≤ 12 months (R/R) large B-cell lymphoma (LBCL)...OBJECTIVES: CAR-T cell therapies such as lisocabtagene maraleucel (liso-cel) have transformed the treatment of patients with second line primary refractory or early relapsed ≤ 12 months (R/R) large B-cell lymphoma (LBCL). The objective of this study was to assess the cost-effectiveness of liso-cel compared to standard of care (SOC) to treat R/R LBCL in France. METHODS: A 3-health-state model was developed to compare liso-cel to SOC over 20 years in France. Efficacy and safety were extrapolated from the TRANSFORM trial (NCT03575351), or DESCAR-T (registry of patients treated with a CAR-T in France). Costs were calculated using French-specific sources. Outcomes were quality-adjusted life years (QALY), life-years (LY), total costs, incremental cost-utility and cost-effectiveness ratios (ICUR, ICER). Probabilistic sensitivity analysis (PSA) was conducted to assess the robustness of the results. RESULTS: Liso-cel generated 5.7 QALY (6.4 LY) for a €265 907. SOC generated 4.4 QALY (5.1 LY) for €233 903. ICUR and ICER were estimated at €24 580/QALY and €23 464/LY gained versus SOC. PSA showed that liso-cel was more effective and more costly in 92% of the simulations. CONCLUSIONS: Liso-cel is cost-effective versus SOC to treat R/R LBCL patients in France. Generation of long-term real-world data is needed in order to validate these findings.
OBJECTIVES: Our aim was to gain deeper insight into the genetic susceptibility of iron deficiency anemia (IDA). METHODS: We performed the first multi-ancestry meta-analysis of genome-wide association study (GWAS), which...OBJECTIVES: Our aim was to gain deeper insight into the genetic susceptibility of iron deficiency anemia (IDA). METHODS: We performed the first multi-ancestry meta-analysis of genome-wide association study (GWAS), which included 113 055 IDA cases and 1 783 936 healthy controls. RESULTS: Through multi-ancestry meta-analysis, 31 risk loci were identified, alongside 703 candidate genes indicated and 47 genes prioritized for IDA. Heritability analyses demonstrated that the liability scale heritability was 3.1% ± 0.2%, whereas an estimated 43.92 million effective sample size would be required to explain 90% of the phenotypic variance. Gene enrichment analysis, gene-set analyses, and genetic correlation studies revealed that IDA-related genes were enriched in whole blood, influenced the role of HFE (hemochromatosis gene) in regulating systemic iron homeostasis, and showed positive correlations with inflammatory diseases, psychological diseases, and cardiovascular diseases. Finally, gene-based prioritized analysis and gene-drug interaction analysis identified some potential targets (e.g., BLK), while drug repurposing approaches highlighted exploratory drug candidates (e.g., folic acid) for IDA. CONCLUSION: We identified 31 novel risk loci for IDA and further characterized its genetic architecture.
Skafi M, Caserta S, Vigna E
… +10 more, Bruzzese A, Amodio N, Lucia E, Olivito V, Labanca C, Mendicino F, Alvaro ME, Morabito F, Martino EA, Gentile M
Eur J Haematol
· 2026 May · PMID 41631494
·
Full text
Diffuse large B-cell lymphoma (DLBCL) remains the most common aggressive lymphoma, representing a biologically heterogeneous disease with diverse clinical behaviors. For more than two decades, R-CHOP has been the corners...Diffuse large B-cell lymphoma (DLBCL) remains the most common aggressive lymphoma, representing a biologically heterogeneous disease with diverse clinical behaviors. For more than two decades, R-CHOP has been the cornerstone of frontline treatment, curing approximately two-thirds of patients. Despite this success, a substantial subset-particularly those with high-risk biology, double-hit genetics, activated B-cell-like (ABC) subtype, or adverse clinical features-still experience relapse or refractory disease. Recent advances in lymphoma biology, immunotherapy, and targeted therapy have stimulated intense interest in improving frontline outcomes. Strategies include optimizing cytotoxic backbone regimens, incorporating antibody-drug conjugates (ADCs), immunomodulatory agents (IMiDs), bispecific antibodies, and exploring the feasibility of frontline CAR-T cell therapy. This review provides a comprehensive and discursive synthesis of the biological rationale, clinical evidence, trial results, and practical considerations shaping contemporary frontline treatment. We highlight the emerging role of molecular subtyping, the tumor microenvironment, and high-risk biomarkers, while discussing ongoing challenges and opportunities in integrating novel modalities into standard practice. Although R-CHOP remains the universal backbone, the therapeutic landscape is entering a transformative era, with polatuzumab-based regimens, bispecific combinations, and precision-guided approaches positioned to redefine frontline care for selected subgroups.
Venous thromboembolism presents a critical complication in hematologic malignancies, profoundly affecting patient outcomes. Traditional anticoagulant options, low-molecular-weight heparin and vitamin K antagonists, encou...Venous thromboembolism presents a critical complication in hematologic malignancies, profoundly affecting patient outcomes. Traditional anticoagulant options, low-molecular-weight heparin and vitamin K antagonists, encounter significant limitations, especially concerning bleeding risks exacerbated by chemotherapy-induced thrombocytopenia. Direct oral anticoagulants (DOACs), including factor Xa inhibitors (apixaban, rivaroxaban, edoxaban) and thrombin inhibitors (dabigatran), have emerged as appealing alternatives due to their ease of use, predictable pharmacokinetics, and reduced monitoring requirements. However, their safety and optimal use remain uncertain in hematologic malignancies due to underrepresentation in clinical trials and specific bleeding risks. This review comprehensively summarizes current evidence regarding DOAC safety, efficacy, and clinical management considerations in leukemia, lymphoma, multiple myeloma, and myeloproliferative neoplasms. It emphasizes individualized anticoagulation strategies, highlights existing evidence gaps, and outlines future research priorities, particularly the safe application of DOACs in severe thrombocytopenia and interactions with targeted therapies. Ultimately, tailored anticoagulant approaches are essential to optimizing patient outcomes in this complex patient population.
IMPORTANCE: Blood type has been proposed as a potential factor in cancer susceptibility; however, its role in childhood leukemia remains unclear. Prior studies have yielded conflicting results, and data from pediatric po...IMPORTANCE: Blood type has been proposed as a potential factor in cancer susceptibility; however, its role in childhood leukemia remains unclear. Prior studies have yielded conflicting results, and data from pediatric populations are limited. OBJECTIVE: This study examines whether ABO/Rh blood types are differentially distributed across acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML) subtypes in children. DESIGN: A retrospective cohort study was conducted that included 540 children aged 0-18 years diagnosed with leukemia between January 2010 and December 2023. Statistical associations were tested using χ tests and ANOVA (R v4.1.3). SETTING: Database was collected from the national electronic health records from Clalit Health Services, Israel's largest healthcare provider. PARTICIPANTS: A total of 540 pediatric oncologic patients were identified. Leukemia subtypes were distributed as acute lymphoblastic leukemia, acute myeloid leukemia, or chronic myeloid leukemia. Other data collected included blood type with its Rh type, age, sex, ethnicity, and disease outcome. RESULTS: No statistically significant association was found between blood type and leukemia subtypes (χ = 6.3, p = 0.600). This remained true after adjusting for age, sex, and ethnicity (p values > 0.05). Survival status (alive/dead as of December 31, 2023) did not differ significantly by blood type (p = 0.774), although O patients showed the highest survival rate (94.1%) and AB the lowest (82.9%). No differences were observed in blood type distribution by sex (p = 0.892) or ethnicity (p = 0.910). Subgroup analyses revealed slight numerical trends, such as a higher proportion of O among AML cases (44.1%), but these lacked statistical power due to small sample sizes (AML n = 34, CML n = 10). Multivariable logistic regression showed no significant associations (all adjusted ORs 0.65-1.10; 95% CIs crossing 1.0). CONCLUSION: In this cohort of pediatric leukemia patients, ABO/Rh blood types were not significantly associated with specific leukemia subtypes or survival outcomes. Because this study lacks a control group from the general population, it does not assess whether blood type influences the risk of developing leukemia; rather, it evaluates whether blood type is differentially distributed across leukemia subtypes among diagnosed cases. Our study contributes important evidence from a region with distinct blood type demographics and supports the need for future larger, multi-center studies to explore subtle associations in rare subtypes and blood groups.
BACKGROUND: Long-term central venous catheters (CVCs) play a critical role in the management of pediatric patients with chronic illnesses, particularly in oncology. These devices provide reliable vascular access for the...BACKGROUND: Long-term central venous catheters (CVCs) play a critical role in the management of pediatric patients with chronic illnesses, particularly in oncology. These devices provide reliable vascular access for the administration of chemotherapy, total parenteral nutrition, antibiotics, blood products, and frequent blood sampling. OBJECTIVE: Review the etiology, complications, and management of retained long-term central venous catheters in children. METHODS: This review analyzes existing literature and clinical experience to highlight mechanisms of catheter adherence and embolization, with a focus on pediatric-specific challenges. RESULTS: Prolonged catheterization may lead to endothelial injury and fibrotic adherence of the catheter to the vessel wall. Catheter fracture with embolization is a rare but serious complication. Management includes surgical, endovascular, and conservative approaches. Pediatric-specific ethical considerations are vital when fragments are left in situ. CONCLUSION: Awareness of risk factors and timely intervention strategies can mitigate complications from retained CVCs. Further research is needed to understand the long-term effects and improve clinical guidelines.
Djambas Khayat C, Dubey L, Inati A
… +8 more, Lissitchkov T, Novik D, Peteva E, Sidonio RF, Taher AT, Vilchevska KV, Vdovin V, Boban A
Eur J Haematol
· 2026 May · PMID 41614378
·
Full text
OBJECTIVES: The WIL-31 study demonstrated efficacy and safety of prophylaxis with the plasma-derived von Willebrand factor/factor VIII concentrate wilate in von Willebrand disease (VWD) of all types and was the only pros...OBJECTIVES: The WIL-31 study demonstrated efficacy and safety of prophylaxis with the plasma-derived von Willebrand factor/factor VIII concentrate wilate in von Willebrand disease (VWD) of all types and was the only prospective study with an on-demand run-in study as an intra-individual comparator. This subgroup analysis examines the efficacy of wilate prophylaxis in patients with type 3 VWD in WIL-31. METHODS: Patients received 20-40 IU/kg wilate prophylaxis 2-3 times weekly for 12 months. RESULTS: Twenty-two patients in WIL-31 had type 3 VWD. Mean total annualized bleeding rate (ABRs) during on-demand versus prophylaxis was 37.1 versus 5.2 (86% reduction). During prophylaxis, 115 bleeds occurred, most (95%) of which were minor; the most common bleeding site was the nose (40% of bleeds). Mean overall spontaneous ABRs during on-demand versus prophylaxis were 26.5 versus 2.8 (89% reduction); mean treated spontaneous ABRs were 20.3 versus 1.4, respectively (93% reduction). ABRs were reduced further during the second 6 months of prophylaxis versus the first 6 months. Results were consistent in subgroups by age. No serious adverse events related to study treatment and no thrombotic events were observed. CONCLUSIONS: Prophylaxis with wilate was effective and well tolerated in patients with type 3 VWD, in all age groups. TRIAL REGISTRATION: NCT04052698; https://clinicaltrials.gov/study/NCT04052698.
Although chimeric antigen receptor (CAR)-T cells targeting B-cell maturation antigen (BCMA) have significantly advanced multiple myeloma (MM) therapy, many patients eventually progress, prompting the search for the most...Although chimeric antigen receptor (CAR)-T cells targeting B-cell maturation antigen (BCMA) have significantly advanced multiple myeloma (MM) therapy, many patients eventually progress, prompting the search for the most effective salvage regimens. To address this demand, we performed a random-effects meta-analysis evaluating response rates to salvage treatments after anti-BCMA CAR-T failure. We identified 36 eligible studies comprising 476 patients and seven distinct interventions through systematic database screening. Among them, bispecific antibodies (bsAbs) were the most common choice, followed by anti-BCMA CAR-T cells. We separately assessed response rates to both first- and any subsequent (combined)-line salvage interventions. In the first-line setting, selinexor-based regimens yielded the highest overall response rates (ORR) of 67% (95% CI: 38%-91%), followed by bsAbs (60%; 95% CI: 43%-76%). In the combined setting, anti-GPRC5D CAR-T cells achieved the highest ORR (88%; 95% CI: 65%-100%), followed by anti-BCMA CAR-T cells (75%; 95% CI: 42%-98%). Belantamab mafodotin demonstrated the lowest efficacy (0%; 95% CI: 0%-17%). Complete response rates remained low across all interventions (range: 0%-40%). Heterogeneity investigations revealed superior responses with human/humanized anti-BCMA CAR-T constructs compared with the animal-based receptors. In summary, our meta-analysis suggested that CAR-T cells and bsAbs are suitable for salvage use after anti-BCMA CAR-T failure in MM. Trial Registration: PROSPERO number: CRD42024621077.
Hernani R, Albert E, Hernani-Morales C
… +20 more, Zúñiga S, Benzaquén A, González-Castillo L, Colomer E, Morell J, Català-Senent JF, Piñana JL, Giménez E, Pérez A, Hernández-Boluda JC, Arroyo I, Rivada M, Barber T, Alemany T, Santacatalina E, Rentero-Garrido P, Terol MJ, Díaz R, Navarro D, Solano C
Eur J Haematol
· 2026 May · PMID 41582602
·
Full text
The interplay between the commensal microbiota and the mammalian immune system may influence the outcomes of T cell-driven cancer immunotherapies. However, clinical studies supporting microbiota-based interventions in ch...The interplay between the commensal microbiota and the mammalian immune system may influence the outcomes of T cell-driven cancer immunotherapies. However, clinical studies supporting microbiota-based interventions in chimeric antigen receptor T-cell (CAR-T) therapy remain scarce. This study included 30 adult patients with B-cell lymphoma treated with axicabtagene ciloleucel (axi-cel) or 4-1BB investigational product. Shotgun metagenomics sequencing (SMS) of fecal samples, collected before lymphodepletion and 1 month post infusion, enabled species-level resolution. We also trained 25 microbiome-based machine-learning (ML) models for response prediction. Neither prior "high-risk" antibiotics exposure nor alpha diversity influenced toxicity, response, or survival. However, dysbiosis was observed between 11 healthy controls and patients, particularly in those treated with axi-cel. SMS identified species associated with clinical outcomes. Increased abundance of Alistipes senegalensis and Alistipes onderdonkii correlated with lower neurotoxicity and improved survival, respectively. Bifidobacterium longum was associated with reduced cytokine release syndrome, whereas Bifidobacterium adolescentis , Bifidobacterium bifidum , and Bifidobacterium breve correlated with poorer survival. ML models demonstrated strong predictive performance, with some identifying non-responders using only six species selected by the Boruta method ( Bacteroides xylanisolvens , Bifidobacterium bifidum , Bifidobacterium breve , Eubacteriaceae bacterium Marseille-Q4139, Negativibacillus massiliensis, and Sellimonas intestinalis). These findings deepen current knowledge and support prospective microbiota-based strategies in CAR-T therapy.