European Journal of Haematology最新文献

Response assessment during treatment of multiple myeloma (MM) typically relies on immunofixation and serum electrophoresis. However, low levels of IgG and especially IgA paraprotein are difficult to quantify reliably. The Hevylite Assay quantifies the kappa and lambda fractions of IgG and IgA separately and is useful to determine response to therapy. Using serum samples of 360 evaluable patients from the prospective GMMG-MM5 trial (EudraCT-No. 2010-019173-16) we assessed the normalization of the kappa/lambda ratio with the Hevylite Assay (HLCr) at baseline, after induction, mobilization, autologous blood stem cell transplantation, consolidation and every three months during maintenance or follow-up within two years after the end of consolidation. We observed a steady increase in the proportion of patients with normalized HLCr over the course of therapyAchieving HLCr normalization any time until the end of consolidation was associated with a trend towards a prolonged progression-free survival (PFS; hazard ratio (HR) = 0.75, 95% confidence interval (95% CI) = 0.56-1.01, p = 0.06) but not overall survival (OS; HR = 0.94, 95% CI = 0.69-1.26, p = 0.66) in multivariable time-dependent Cox regression analyses. Using a landmark analysis from the end of consolidation there was again a marginally statistically significant effect of HLCr normalization by the end of consolidation on PFS using a multivariable Cox model on the subset of the two study arms with continuous lenalidomide maintenance (HR 0.61, 95% CI 0.37-1.02, p = 0.06). No such effect was observed in study arms in which maintenance was only applied to patients not in CR at the end of consolidation. In conclusion, our analysis of the Hevylite Assay in patients with IgG or IgA myeloma from the GMMG-MM5 study did not find evidence to support the general use of HLCr normalization as a response parameter for predicting PFS or OS. However, the differential effects of HLCr normalization depending on the way in which treatment was adapted to response may be of interest for future study designs on response-adapted therapy. Trial Registration: ISRCTN05622749.

Introduction: Prognostic models in Waldenström's macroglobulinemia (WM) are typically static, baseline tools applied before treatment initiation and do not account for dynamic post-treatment factors. We evaluated time to next treatment within 24 months (TTNT24), as a prognostic marker in symptomatic patients, and time to lymphoma treatment within 24 months (TTLT24) in initially observed asymptomatic patients.

Methods: In this observational cohort study, patients diagnosed with lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) in Region Zealand from 2000 to 2023 were identified using Danish national registries and health records. TTNT24 was defined as initiation of second-line treatment within 24 months of first-line therapy. TTLT24 was defined as lymphoma-directed treatment initiated within 24 months of diagnosis in initially asymptomatic patients.

Results: Among 526 LPL/WM patients, 218 symptomatic patients were evaluated for TTNT24 with 33 (15%) patients receiving second-line treatment within 24 months. TTNT24-positive patients demonstrated inferior overall and lymphoma-related survival compared to TTNT24-negative patients. TTNT24 remained significant in multivariate analysis. Among 310 asymptomatic patients, TTLT24 was significantly associated only with lymphoma-related survival.

Conclusion: TTNT24 and TTLT24 may serve as dynamic prognostic markers in real-world LPL/WM populations. Their relevance in the era of targeted therapies warrants further investigation.

The utilization of eltrombopag (EPAG) in the management of post allogenic hematopoietic cell transplant (HCT) cytopenia has exhibited promising outcomes. Isolated thrombocytopenia and poor graft function (PGF) are factors that adversely influence transplant outcomes and patient well-being. This retrospective study aims to assess EPAG efficacy in this context as a primary outcome and evaluate early EPAG tapering post complete response (CR) for cost efficiency and response durability as a secondary outcome. We analyzed 39 patients who underwent allogeneic HCT; EPAG was administered to 89.7% of patients for PGF and 10.3% for isolated thrombocytopenia. The overall response rate (ORR) after 4 weeks of EPAG treatment was 71.8%, with 48.7% achieving a complete response (CR). Early tapering of EPAG post-CR was explored for cost benefit among responders. Early tapering was defined as the start of tapering after 4 weeks of achieving CR and was found to be associated with significant response durability with a trend towards cost effectiveness. Eltrombopag response was independent of megakaryocyte number or density prior to drug initiation. The study suggests EPAG as a safe treatment for PGF and isolated thrombocytopenia post-allogeneic HCT and proposes early drug tapering as a potentially cost-beneficial approach.

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.

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.