Therapeutic Advances in Hematology最新文献

Background: Patients with lower-risk myelodysplastic syndromes (MDS) may experience anemia and a high transfusion burden, alongside a risk of progression to acute myeloid leukemia. Luspatercept, a recombinant fusion protein that acts as an erythroid maturation agent, was FDA/EMA-approved in 2020 based on the phase III MEDALIST trial. There remains an unmet need for anemia treatment in Asian patients for whom red blood cell (RBC) transfusion is a standard of care, and in whom rates/severity of anemia and serum erythropoietin levels are often higher versus Western patients.

Objectives: The objective of this study was to assess the efficacy, safety, and tolerability of luspatercept in Asian patients with anemia due to transfusion-dependent lower-risk MDS with ring sideroblasts.

Design: This was a phase II, single-arm, interventional bridging study (NCT04477850).

Methods: Patients from China and Japan with very low-, low-, or intermediate-risk MDS with ring sideroblasts who were RBC transfusion-dependent received subcutaneous luspatercept starting at 1.0 mg/kg every 3 weeks. The primary endpoint was RBC transfusion independence (TI) ⩾8 weeks (weeks 1-24).

Results: There was a statistically significant, clinically meaningful improvement of anemia in Asian patients; 60% (n = 18, p < 0.0001) achieved RBC-TI for ⩾8 weeks and 43% (n = 13) for ⩾12 weeks (weeks 1-24). Safety was consistent with the known profile of luspatercept in MDS.

Conclusion: These results support luspatercept as a well-tolerated, efficacious alternative to transfusions for Asian patients with lower-risk MDS, who tend to have more severe anemia. Trial registration: clinicaltrials.gov, NCT04477850.

Background: Renal impairment is one of the common characteristics of multiple myeloma (MM) and makes management of MM more complicated. Even though monoclonal antibodies targeting CD38 have wildly succeeded in treating MM, the addition of anti-CD38 monoclonal antibodies to standard therapy to treat MM patients with renal insufficiency is still poorly studied.

Objectives: This study aims to evaluate whether using anti-CD38 monoclonal antibody-based immunotherapy would improve the prognosis of MM patients with renal insufficiency.

Design: This is a systematic review and meta-analysis.

Data sources and methods: We searched Scopus, PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Ovid Embase, and Web of Science Core Collection for randomized controlled trials that enrolled patients with MM who received CD38-targeting monoclonal antibody regimens and reported the efficacy and survival of MM with renal insufficiency. We then performed a meta-analysis to estimate the efficacy of adding anti-CD38 monoclonal antibodies to backbone regimens in MM with renal insufficiency.

Results: In 7594 studies screened, 12 phase III trials were eligible, including 5 trials for newly diagnosed MM (NDMM; 3194 patients; 1261 with renal insufficiency) and 7 trials for relapsed refractory MM (RRMM; 2657 patients; 648 with renal insufficiency). Among NDMM patients with renal insufficiency, the addition of anti-CD38 monoclonal antibody to backbone regimens was associated with improved progression-free survival (PFS; pooled HR, 0.50; 95% CI, 0.38-0.67; p < 0.001), with little evidence of heterogeneity (Cochran Q, p = 0.19; I ² = 34.7%). Similar results were seen among RRMM patients with renal insufficiency (pooled HR, 0.46; 95% CI, 0.37-0.57; p < 0.001), with no evidence of heterogeneity (Cochran Q, p = 0.89; I ² = 0%). Similarly, the addition of anti-CD38 monoclonal antibody in RRMM among patients with renal insufficiency was associated with improved overall survival (OS; pooled HR, 0.70; 95% CI, 0.57-0.88; p = 0.002), with no significant heterogeneity (Cochran Q, p = 0.69; I ² = 0%).

Conclusion: This meta-analysis suggests that the addition of anti-CD38 monoclonal antibodies benefits PFS in both NDMM and RRMM with renal insufficiency and OS in RRMM patients with renal insufficiency.

Background: Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory condition often triggered by malignancies, especially T/NK-cell lymphoma-associated HLH (T/NK-LAHLH). Epstein-Barr virus (EBV) infection is strongly linked to T/NK-LAHLH and worsens prognosis. However, the prognostic value of whole-blood EBV DNA levels in T/NK-LAHLH remains unclear, necessitating further investigation to improve risk assessment and treatment strategies.

Objective: To investigate the clinical characteristics and prognostic significance of whole-blood EBV DNA status in patients with T/NK-LAHLH.

Design: A single-center, retrospective study was conducted, including 85 patients diagnosed with T/NK-LAHLH between January 2017 and August 2022. Patients were categorized based on EBV DNA status, and clinical outcomes were compared.

Methods: EBV DNA levels were quantified using polymerase chain reaction (PCR) assays. Kaplan-Meier survival and Cox regression models to assess overall survival (OS) and identify independent prognostic factors.

Results: A total of 85 T/NK-LAHLH patients were included, with a median age of 52 years (range: 18-81 years) and 60% male. The OS rates at 1, 3, 6, and 12 months were 66.6%, 49.8%, 33.8%, and 28.4%, respectively. Among these patients, 67 (78.8%) were EBV DNA-positive, while 18 (21.2%) were EBV DNA negative. EBV DNA-positive patients exhibited significantly lower platelet and globulin levels, higher IL-10 levels, and prolonged activated partial thromboplastin time compared to EBV DNA-negative patients (p < 0.05). The 6-month OS rate was significantly lower in EBV DNA-positive patients compared to EBV DNA-negative patients (22.5% vs 75.1%, p < 0.001). Multivariate analysis identified EBV DNA positivity as an independent risk factor for shorter 6-month OS (hazard ratio (HR): 4.715; 95% CI: 1.662-13.377; p = 0.004). Among the four patients who underwent allogeneic hematopoietic stem cell transplantation, all achieved complete remission and remained alive at the last follow-up.

Conclusion: Whole-blood EBV DNA positivity is a significant prognostic factor for poor outcomes in T/NK-LAHLH patients. These findings highlight the need for incorporating EBV DNA monitoring into clinical management and further research to refine therapeutic strategies.

Background: We aim to analyze the efficacy and safety of Venetoclax (Ven) added to cladribine + cytarabine + granulocyte colony-stimulating factor (G-CSF) ± idarubicin or mitoxantrone (CLAG ± Ida/Mito) regimen as a salvage treatment of relapsed/refractory acute myeloid leukemia (RR-AML).

Methods: A single-center, retrospective, cohort study was performed. Patients with RR-AML, being treated with CLAG ± Ida/Mito with versus without Ven, were retrospectively studied. The endpoints of this study were to evaluate the rate of composite complete remission (CRc), measurable residual disease (MRD), event-free survival (EFS), overall survival (OS), and relapse between CLAG and CLAG + Ven groups.

Results: Sixty-nine patients were included, with a median age of 37 (range, 18-65) years. Thirty-one patients underwent one cycle of salvage treatment of CLAG ± Ida/Mito with Ven and 38 without. In the CLAG + Ven group, 24 (77.4%) patients acquired response, including 22 (71.0%) with composite complete remission (CRc) and 15 (48.4%) MRD-negative CRc, which was significantly higher than those (CRc 47.4%, p = 0.048; MRD-negative CRc 18.4%, p = 0.008) in the CLAG group. Subgroup analysis showed that patients without response after two courses of induction therapy, or patients with FLT3 mutations seemed to benefit more from CLAG ± Ida/Mito + Ven than CLAG ± Ida/Mito in acquiring CRc. With a median follow-up of 13 (95% CI 10.5-15.5) months, the CLAG + Ven group had a median OS of 22.9 (95% CI 19.6-26.2) months and EFS of 15.7 (95% CI 11.1-20.2) months. In contrast, the CLAG group had a median OS of 18.6 (95% CI 14.7-22.6) months and EFS of 10.7 (95% CI 6.6-14.8) months. Although not statistically significant, patients in the CLAG + Ven group showed a potential survival advantage compared to the CLAG group. AEs including all grade and grade 3/4 occurred at similar frequencies in the two groups.

Conclusions: Ven added to CLAG ± Ida/Mito might improve the outcome of the patients with RR-AML, with well toleration, and a randomized controlled trial is needed to explored.

Being "between Scylla and Charybdis" is an idiom derived from Greek mythology to mean "between a rock and a hard place" and clinicians managing amyloid light-chain (AL) amyloidosis often find themselves in this predicament. AL amyloidosis is caused by monoclonal light chains, most commonly produced by CD-38 positive plasma cells in target organs. The disease usually involves significant cardiac and/or renal involvement, but the systemic nature of the disease often leads to variable and non-specific manifestations that can critically delay early diagnosis and treatment. Here, we present a case series reflecting primarily the cardiologist and hematologist perspective to uniquely illustrate key learnings that we believe have the potential to improve diagnosis timelines, treatment initiation, and ultimately improve outcomes for this severe disease. Through our case series, we illustrate that to achieve an accurate diagnosis, a high degree of clinical suspicion is needed, and we stress the important requirement of substantial multi-disciplinary collaboration. Our experience strongly indicates that AL amyloidosis patients presenting with cardiac symptoms need to be identified and treated rapidly, prior to the development of irreversible cardiotoxicity. In addition, patients without significant cardiac involvement may benefit from rapid initial treatment with daratumumab along with cyclophosphamide-bortezomib-dexamethasone, which can render patients eligible for autologous stem cell transplant (ASCT) or in some instances means they can forgo ASCT completely. Increased awareness of the disease is needed among general cardiologists and hematologists, and specialized centers with the relevant expertise should be willing to accept patients for fast-track evaluation as part of their standard procedures, due to the unique contribution they can offer in the clinical management of this life-threatening disease.

Background: Cytomegalovirus (CMV) infection can lead to significant morbidity and mortality in pediatric hematopoietic stem cell transplant recipients. Early detection of CMV infection is crucial for managing its impact.

Aim: This study aims to evaluate the effectiveness of QuantiFERON-CMV^® (QF-CMV) and QuantiFERON-Monitor^® (QFM) tests in predicting CMV infection and graft-versus-host disease (GvHD) in pediatric hematopoietic stem cell transplant recipients to enhance patient outcomes and support personalized prevention strategies.

Methods: The QF-CMV and QFM tests were used to predict CMV pp65 antigen and GvHD in 24 pediatric hematopoietic stem cell transplant recipients.

Results: Data showed that positive CMV antigenemia (CMV-Ag) increased the risk of GvHD by 21.2%. QF-CMV and QFM were associated with CMV-Ag, with QF-CMV inversely predicting GvHD. Lymphocyte and neutrophil counts were positively linked to both tests.

Conclusion: The findings suggest that QF-CMV and QFM tests could predict GvHD and CMV infection risk and help identify high-risk patients, contributing to personalized prevention strategies and improving CMV treatment. Despite the small sample size, this study is an essential proof of concept due to the unique patient population of pediatric bone marrow stem cell transplant recipients. Further multicenter studies are needed to validate these results.

Background: Adult T-cell leukemia/lymphoma (ATL) is a neoplasm with a high prevalence in certain regions such as southwestern Japan, the Caribbean, sub-Saharan Africa, South America, and Australia. In Colombia, the seroprevalence of human T-cell lymphotropic virus type 1 (HTLV-1) has been reported in specific populations, but there is limited information about the clinical course and management of ATL in the country.

Objectives: To describe the clinical characteristics, treatment patterns, and outcomes of patients diagnosed with HTLV-1-positive ATL in a high-complexity healthcare institution in Colombia and compare these findings with reports from other geographic regions.

Design: Observational retrospective cohort study conducted in a single high-complexity healthcare institution in Cali, Colombia, including patients diagnosed between 2011 and January 2022.

Methods: This study presents an observational retrospective cohort of patients diagnosed with HTLV-1-positive ATL and managed at a high-complexity institution in Cali, Colombia. Eligible patients were adults diagnosed with ATL and HTLV-1 seropositivity, receiving treatment between 2011 and January 2022. Demographic, clinical, and treatment-related variables were collected and analyzed using descriptive and survival analyses.

Results: Thirty-three patients diagnosed with ATL between 2011, and January 2022 were identified and included in the study. Most patients were female (52%) with a median age of 54 years. Acute presentation was the most common (64%), and most patients were identified at Ann Arbor stage 4. Treatment mainly consisted of various chemotherapy protocols, with cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (CHOP)-like regimens being the most frequently used. However, the overall response rate to chemotherapy was low, and most patients experienced complications and toxicities associated with treatment.

Conclusion: This study provides insights into the clinical course and management of ATL in a Colombian population. The findings highlight the predominance of acute presentations, advanced disease stages at diagnosis, and challenges in achieving a complete response with conventional chemotherapy. Further research is needed to improve treatment strategies, identify prognostic markers, and develop more effective therapies for ATL patients in Colombia.

This report describes the cases of two patients with mycosis fungoides and Sézary syndrome (MF/SS) who achieved clinical benefit with mogamulizumab combination therapies. Case 1 is a 56-year-old male with stage IIIB (T4NxM0B1) MF, which later progressed into SS, with ongoing skin symptoms (erythema, lichenified skin, and pruritis) and axillary and inguinal lymphadenomegaly. Skin-directed and systemic therapies failed to achieve a long-lasting response in this patient. Mogamulizumab (1 mg/kg once weekly for 4 weeks; once every 2 weeks thereafter) yielded temporary improvement in skin symptoms, but progression in the skin was confirmed after ~2 months. Subsequently, the combination of mogamulizumab with psoralen plus ultraviolet light A (PUVA) yielded a partial response; however, PUVA was discontinued due to phototoxicity and mogamulizumab was continued as monotherapy. At the latest evaluation, clinical improvement in the skin and reduced lymphadenomegaly were evident with ongoing mogamulizumab monotherapy; the patient is awaiting allogeneic hematopoietic stem cell transplantation. Case 2 is an 80-year-old male with stage IIIB (T4NxM0B1) granulomatous variant MF who presented with diffuse erythema with desquamation, ectropion, and inguinal lymphadenopathy. Treatment with oral prednisone and bexarotene failed to achieve adequate, long-lasting responses. Mogamulizumab (1 mg/kg once weekly for 4 weeks; once every 2 weeks thereafter) monotherapy yielded an initial improvement, characterized by less intense erythema, but the improvement was not sustained. Mogamulizumab was supplemented with oral prednisone and then PUVA; this combination resulted in improvement in the skin. PUVA was stopped due to unavailability, and methotrexate (10 mg once weekly) was initiated alongside continued mogamulizumab; this led to improvement in erythema. The patient continued mogamulizumab plus methotrexate with improving clinical status, prior to their death, which was deemed to be unlikely to be related to treatment. Our experience suggests that, in principle, mogamulizumab can be used in combination with other therapies; however, further research is needed.

Background: The occurrence of adverse events after immunochemotherapy in patients with diffuse large B-cell lymphoma (DLBCL) frequently affects the course of chemotherapy, leading to a further decline in quality of life and survival.

Objectives: The primary objective of this study was to investigate the association between Chinese visceral adiposity index (CVAI), lipid accumulation product (LAP) index and skeletal muscle mass index (SMI) at initial diagnosis and the risk of haematological toxicity following immunochemotherapy in patients with DLBCL.

Design: Retrospective, single-centre study.

Methods: CVAI, LAP and SMI were calculated by combining clinical data of the patients. This study included 213 patients, of whom 117 (55%) patients experienced grades 3-4 haematological toxicity after immunochemotherapy. Participants were divided into four groups (Q1, Q2, Q3, Q4) based on the quartiles of CVAI, LAP and SMI.

Results: In the fully adjusted model, the risk of grades 3-4 haematological toxicity in group with the highest CVAI and LAP was reduced by 75.1% (OR: 0.249, 95% CI: 0.102-0.606, p = 0.002) and by 77.3% (OR: 0.227, 95% CI: 0.095-0.542, p = 0.001) compared to the group with the lowest CVAI and LAP. For SMI, the risk of grades 3-4 haematological toxicities in the group with the highest SMI was reduced by 62.9% compared with the lowest SMI group in the unadjusted model. The multivariable-adjusted restricted cubic spline curves and subgroup interaction analyses further confirmed the robustness of these findings.

Conclusion: The results indicate that DLBCL patients with relatively high CVAI, LAP and SMI at initial diagnosis have a lower risk of severe haematological toxicity following chemotherapy. Therefore, CVAI, LAP and SMI at initial diagnosis are reliable and effective biomarkers for predicting severe haematological toxicity after immunochemotherapy in DLBCL patients.

Trial registration: This is a retrospective study, and no registration on ClinicalTrials.gov.

Background: Macrofocal multiple myeloma (MFMM) is characterized by clonal plasma cells comprising less than 20% of the bone marrow, multiple lytic bone lesions, and the absence of anemia, renal insufficiency, and hypercalcemia. This subtype of multiple myeloma (MM) has a relatively low incidence. Prognostic staging and cytogenetic guidance for MFMM are often insufficient due to the low tumor burden in the bone marrow. Large cohort studies on this subgroup during the era of novel agents are limited.

Objectives: We aim to describe the clinical characteristics and prognostic markers of MFMM patients undergoing treatment with novel agents.

Methods: Consecutive cases of MM patients diagnosed at Peking University People's Hospital and Fu Xing Hospital of Capital Medical University from 2011 to 2023 were screened. A propensity score matching was conducted with a 2:1 ratio, matching classic MM patients to MFMM patients based on clinical variables of age and year of diagnosis.

Results: We identified 91 cases (4%) of MFMM and 182 matched classic MM among 2291 MM patients. The MFMM cohort had a higher proportion of male patients, those with <90% clonal plasma cells in the bone marrow by multiparameter flow cytometry, and patients with extramedullary disease, along with a lower proportion of patients with high-risk cytogenetics or advanced disease staging. MFMM patients demonstrated better overall responses compared to the control cohort (p = 0.027) in those not receiving upfront autologous stem cell transplantation (ASCT). During a median follow-up of 42.8 months for the entire cohort, the MFMM cohort exhibited significantly superior progression-free survival (PFS) and overall survival (OS) compared to the control cohort. In multivariate analysis of the entire cohort, exposure to immunomodulatory drugs and ASCT consolidation in frontline therapy were independently associated with improved PFS and OS. For the MFMM cohort, a Ki-67 index ⩾20% was associated with inferior PFS, providing valuable prognostic information in a group where staging and cytogenetic guidance are often inadequate.

Conclusion: We concluded that treatment strategies for MFMM patients should align with those for standard MM, and a Ki-67 index ⩾20% in biopsy samples of plasmacytoma is associated with inferior PFS.