Hematological Oncology最新文献

Given the paucity of age-specific data about biology, presentation, and treatment outcomes in adults with MZL, we sought to evaluate differences between younger (≤ 70 years) and older (> 70 years) patients with MZL in a large retrospective cohort treated in the contemporary era (2010 onwards). The primary objective was progression-free survival (PFS), while secondary objectives included the evaluation of overall survival (OS) and the cumulative incidence of transformation between the 2 groups. A total of 598 patients were included in the analysis and among these 32% were > 70 years of age. There were no age-based differences in the prevalence of NMZL, SMZL, and EMZL. Older patients had a higher incidence of adverse prognostic features at diagnosis such as worse performance status, advanced stage disease, and bone marrow involvement, yet were more likely to be treated with single-agent rituximab than chemoimmunotherapy. Age > 70 years was associated with inferior PFS and OS after controlling for clinically relevant risk factors and accounting for differences in first-line treatment. Receipt of rituximab monotherapy was associated with significantly inferior PFS overall, however, the type of first-line therapy did not impact OS in any group. Our data suggests that despite the development of new drugs for MZL, age remains an independent predictor of inferior outcomes. Investigation of targeted therapy combinations in the first-line setting may yield the required balance of efficacy and toxicity in older adults with MZL.

Immunochemotherapy has demonstrated high cure rates in primary mediastinal large B-cell lymphoma (PMBCL). Recent findings from the IELSG 37 study show that certain specific dose-dense treatment regimens are more likely to eliminate the need for consolidative radiation therapy, thereby reducing long-term toxicity. Here, we report our experience with DA-R-EPOCH in a cohort of 70 patients treated at our cancer center. This retrospective, observational, single-center study includes patients treated between 2013 and 2021. Treatment response was evaluated using positron emission tomography-computed tomography (PET-CT) scans and assessed according to the Deauville Score. With a median follow-up of 36.4 months, 29% of patients achieved a complete metabolic response (CMR) on interim PET-CT, while 71% achieved CMR at the end of treatment. Despite these results, 3-year overall survival (OS) and progression-free survival (PFS) rates were 99% and 93%, respectively. Our findings highlight the importance of tailoring treatment regimens, allowing for reduced reliance on consolidative therapies in line with recent advancements. Notably, none of the patients who achieved CMR on interim PET-CT experienced relapse, and no disease progression was observed beyond 1 year after completing DA-R-EPOCH. Additionally, our results indicate that dose intensification beyond level 2 does not appear to improve survival, emphasizing the important implications for minimizing treatment-related toxicity. We also analyzed the management and outcomes of refractory and relapsed cases, underscoring the challenges in treating non-responding patients identified by interim PET-CT, the limited efficacy of salvage immunochemotherapy, and the interesting role of radiation therapy in these cases.

Localized light chain amyloidosis (loc-AL) is a rare disorder characterized by localized deposition of misfolded AL fibrils. There are limited data on patterns of disease presentation and long-term outcomes. In this study, we retrospectively reviewed 146 patients with loc-AL at our institution between January 1, 2010, and March 1, 2024. We excluded patients with evidence of systemic AL amyloidosis. We calculated local (PFS_L) and systemic (PFS_s) progression free survival (PFS) and overall survival (OS) using the Kaplan-Meier method. We found that loc-AL most commonly involved the respiratory (26%), gastrointestinal (17%), head and neck (17%) and genitourinary (10%) systems. Overall, 51% patients were asymptomatic at presentation, and 16% had a co-existent autoimmune disease. First line management included observation (52%), surgical resection (39%), chemotherapy (3%), and radiation (2%). Most patients (59%) had a response with first-line therapy. The median PFS_L was ∼15 years (10-year PFS_L 68%), and median OS was not reached (10-year OS 83%). None of the patients had progression to systemic amyloidosis. Seventeen patients had local recurrence and required second line therapy. In conclusion, loc-AL has an excellent prognosis and does not progress to systemic AL amyloidosis. Observation and/or surgical removal are usually adequate first-line approaches; however, a small proportion of patients can relapse locally requiring repeated interventions for symptom control.

Daratumumab in combination with lenalidomide and dexamethasone (DRd) and bortezomib in combination with lenalidomide and dexamethasone (VRd) are guideline-recommended preferred regimens for initial treatment of transplant-ineligible (TIE) patients with newly diagnosed multiple myeloma (NDMM). This study aimed to systematically identify evidence on the clinical effectiveness of DRd and VRd as first-line treatments for patients with TIE NDMM and to conduct a meta-analysis. Ovid MEDLINE, Embase, and Cochrane Library were searched from January 2019 to June 2023, along with key congresses from January 2018 to June 2023. Bibliographies of relevant systematic literature reviews (SLR) were hand-searched. Randomized controlled trials and appropriately adjusted non-randomized studies comparing DRd versus VRd as first-line treatment for TIE NDMM were included. Overall, five records from three unique studies were identified. The fixed-effects meta-analysis showed a lower risk of disease progression or death with DRd versus VRd using the naïve approach (hazard ratio [HR]: 0.60; 95% confidence interval [CI]: 0.46, 0.77) as well as with the adjusted approach, which accounted for both double counting (i.e., two studies shared one comparison) and variance inflation due to studies with moderate and high risk of bias (HR: 0.56; 95% CI: 0.39, 0.82). In the absence of clinical trials with head-to-head comparison of these treatment regimens, these results could help inform the selection of optimal first-line treatment for TIE NDMM patients.

Myelofibrosis (MF) is characterized by anemia, constitutional symptoms, hepatosplenomegaly and bone marrow fibrosis, and is associated with poor survival. The janus kinase inhibitor (JAKi) ruxolitinib has been the mainstay of treatment for over a decade. Despite demonstrated symptomatic and quality of life improvement, unmet clinical needs persist. A literature review identified promising novel targeted treatment options in MF using pre-set selection criteria (available Phase 2 or 3 data, minimum enrollment of 50 patients, trial end date within the last 5 years). Available data for novel and approved therapies were extracted, tabulated, and analyzed for clinical relevancy. From an initial shortlist of 48, 16 retained molecules were selected for inclusion. Other JAKi (pacritinib, momelotinib, jaktinib) address treatment-related cytopenia, expanding the therapeutic utility of this class of agents to patients with baseline anemia or thrombocytopenia. Novel candidates exploit multiple molecular pathways, and offer the potential to improve the management of MF-associated cytopenia (imetelstat, pelabresib, navitoclax, selinexor, luspatercept, sotatercept, elritercept, LCL161, bomedemstat) and recover bone marrow fibrosis (imetelstat, pelabresib, navitoclax and bomedemstat). It remains to be seen if these newer agents can induce any remission in MF and enable patients to come off therapy, but the future is beginning to look much brighter.