Blood Cancer Journal最新文献

This multicenter retrospective study by GETH-TC validates the prognostic value of the Allo-HCT Refined ELN 2022 risk classification in allografted AML patients. The new classification refines the ELN 2022 risk classification, dividing adverse-risk patients into two subgroups: Adv-Plus (AdvP), including those with complex karyotype, MECOM (EVI1) rearrangement, or TP53 mutations/del(17p), and an additional adverse group (Adv*). The study included 651 AML patients treated with at least one line of anthracycline-based induction therapy and in complete remission. According to the Allo-HCT Refined ELN 2022 risk classification, 19.4% (n = 126) patients were classified into the Favorable (Fav) risk, 38.1% (n = 248) into the Intermediate (Int) risk, 27.2% (n = 177) in the Adv* and 15.4% (n = 100) in the AdvP. Outcomes were significantly poorer for patients allocated in the AdvP risk group (5-year OS rate: 32.3%, 5-year LFS rate: 24.3%, both p < 0.001 with the rest of subgroups) and a higher CIR (5-year CIR: 64.3%, p < 0.001). Patients in the Adv* risk group had similar outcomes than patients in the Int risk group (5-year OS rate: 70.2% vs. 66.7%, p = 0.69, 5-year LFS rate: 63.8% vs. 55.9%, p = 0.33). Multivariate analysis confirmed the dismal outcomes for AdvP patients for OS: Hazard Ratio (HR) = 3.05, and LFS: HR = 2.66, both p < 0.001. Our findings validate the Allo-HCT Refined ELN 2022 classification as a robust prognostic tool, particularly highlighting the poor outcomes for the AdvP subgroup.

The persistence of high relapse rates and therapy resistance continues to challenge the effective management of multiple myeloma (MM). The identification of novel MM-specific molecular markers could ameliorate risk-stratification tools and accurately identify high-risk patients towards personalized prognosis and therapy. miRNA-seq analysis of CD138+ plasma cells (n = 24) unveiled miR-221-3p and miR-222-3p (miR-221/222 cluster) as the most downregulated miRNAs in R-ISS III compared to R-ISS I/II patients. Subsequently, miR-221/222 levels were quantified by RT-qPCR in CD138+ plasma cells of our screening cohort (n = 141), assessing patients’ mortality and disease progression as clinical endpoints. Internal validation was performed by bootstrap analysis, while clinical benefit was estimated by decision curve analysis. Kryukov et al. (n = 149) and Aass et al. (n = 86) served as institutional-independent validation cohorts. Loss of miR-221/222 cluster was strongly associated with patients’ short-term progression and poor overall survival, which was confirmed by Kryukov et al. and Aass et al. validation cohorts. Intriguingly, miR-221/222-fitted multivariate models offered superior risk-stratification within R-ISS staging and risk-based cytogenetics. Moreover, miR-221/222 loss could effectively discriminate optimal 1st-line treatment responders with inferior treatment outcome. Our study identified the loss of miR-221/222 cluster as a powerful independent predictor of patients’ post-treatment progression, ameliorating prognosis and supporting precision medicine in MM.

Treatment of Burkitt Lymphoma/Leukemia (BL/L) in adults has evolved from the use of pediatric inspired regimens (CODOX-M/IVAC, hyper-CVAD, GMALL) to the use of lower intensity EPOCH regimens. The addition of rituximab has led to improvements in overall survival. Survival with these regimens in the real world was shown to be inferior as compared to those found in the prospective trials. In low- and middle-income country (LMIC) settings, unique problems like delays in seeking care, treatment-related toxicities, and treatment abandonment may hamper outcomes. We performed this retrospective multicenter analysis amongst eight centers in India, to study the disease characteristics, treatment patterns, outcomes, and prognostic factors for BL/L. Between 2012–2019, 265 patients were treated at these centers. Common regimens were methotrexate-based (N – 108(40.7%)) and EPOCH-based (N – 103(38.8%)). After a median follow-up of 42 months, 3-year event-free and overall survival were 58% (95% CI: 55–61%) and 66% (95%CI: 63–69%) respectively. In a propensity matched analysis comparing methotrexate-based protocol and EPOCH-based protocol, the EFS and OS were similar with both the protocols. EPOCH based protocol yielded inferior outcomes in patients with bone marrow, and central nervous system involvement. Factors like rituximab incorporation, baseline ECOG PS 0–2, lower serum LDH, early stage(I/II), achievement of complete response (CR) and low/intermediate BL-IPI risk scores were associated with better survival. However, on multivariable analysis, major factor impacting outcome was achievement of CR.

Although treatment with standard frontline therapies, including a FLT3 inhibitor (FLT3i) reduces AML burden and achieves clinical remissions, most patients with AML with FLT3 mutation relapse due to therapy-resistant stem/progenitor cells. The core ATPases, BRG1 (SMARCA4) and BRM (SMARCA2) of the canonical (c) BAF (BRG1/BRM-associated factor) complex is a dependency in AML cells, including those harboring FLT3 mutations. We have previously reported that treatment with FHD-286, a BRG1/BRM ATPases inhibitor, induces differentiation and loss of viability of AML stem/progenitor cells. Findings of present studies demonstrate that treatment with FHD-286 induces lethality in AML cells, regardless of sensitivity or resistance to FLT3i. This efficacy is associated with the induction of gene-expression perturbations responsible for growth inhibition, differentiation, as well as a reduced AML-initiating potential of the AML cells. Additionally, co-treatment with FHD-286 and FLT3i exerts superior pre-clinical efficacy against AML cells and patient-derived (PD) xenograft (PDX) models of AML with FLT3 mutations.

The treatment landscape for transplant-eligible patients with newly diagnosed multiple myeloma (TE-NDMM) has evolved with the introduction of daratumumab-based quadruplet regimens. Adding daratumumab to traditional triplet regimens has demonstrated improved response rates and progression-free survival (PFS). However, the impact on long-term outcomes, particularly overall survival (OS), remains uncertain. This systematic review and meta-analysis aimed to compare the survival outcomes of these quadruplet regimens with triplets. Conducted in adherence to Cochrane Collaboration and PRISMA guidelines and registered on PROSPERO (CRD42024571946), the study involved searching PubMed, Embase, and Cochrane databases, from inception to June 2024. We included randomized clinical trials (RCT) and non-randomized controlled studies (NRCS) that compared daratumumab-based quadruplet regimens to triplets, focusing on OS and PFS, with a minimum follow-up of 18 months. The meta-analysis included 3327 TE-NDMM patients from four studies, comprising three RCT and one NRCS. Daratumumab-based regimens were administered to 1328 (40%) patients. The analysis revealed that daratumumab-based quadruplet regimens significantly improved both OS (pooled HR 0.60; 95% CI 0.48–0.75; P < 0.00001; I² = 0%) and PFS (pooled HR 0.49; 95% CI 0.37–0.65; P < 0.00001; I² = 52%). A per-protocol subgroup analysis comparing D-VRD to VRD further confirmed these benefits, with significant improvements in both OS (pooled HR 0.68; 95% CI 0.48–0.97; P = 0.03; I² = 0%) and PFS (pooled HR 0.41; 95% CI 0.31–0.54; P < 0.00001; I² = 0%). This meta-analysis consolidates evidence that daratumumab-based quadruplet regimens significantly improve OS, compared to triplet regimens for TE-NDMM patients.

While initial trials led to the accelerated approval of belantamab mafodotin, a BCMA-directed antibody-drug conjugate, confirmatory trials failed to establish benefit from this therapy for patients with relapsed refractory multiple myeloma (RRMM), eventually leading to its withdrawal from commercial use. With an imminent approval as an effective combination therapy, as seen in recent randomized trials, we report real-world clinical outcomes with belantamab mafodotin in 81 RRMM patients. With a median of 5 (range 2–15) prior lines of therapy, 92, 45, and 15% of the patients were triple-class refractory, penta-class refractory, and BCMA-refractory. More than half (57%) of the patients had high-risk cytogenetics, 37% had extramedullary disease (EMD), and 67% of the patients would have been considered ineligible for the DREAMM-2 trial. The best overall response (ORR) and complete response rates were 40.0 and 15.0%, respectively. ORRs were lower in patients with EMD, BCMA-refractory, and penta-refractory disease at 23, 17, and 24%, respectively. All-grade ocular toxicity was seen in 69% of patients, with grade 3+ events in 43%. Grade 3+ hematological toxicities included neutropenia (20%), anemia (28%), and thrombocytopenia (31%). With a median follow-up of 11.3 (0.3–44.6) months for the entire population, median PFS and OS were 5 (1–20) months and 12 (3–28) months, respectively. Presence of EMD was the only predictor of both PFS and OS on multivariable analysis. Compared to the pivotal trial and despite several high-risk disease features, belantamab mafodotin demonstrated comparable efficacy and safety in this real-world patient population.