European Journal of Haematology最新文献

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.

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^-5 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.

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 × 10³/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^-14, respectively). In > 75% of high-grade ICANS cases, 1 day before its onset, platelet counts were < 100 × 10⁹/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 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.

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  $\ge$  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 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.

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.

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.