Erythropoiesis and iron metabolism are closely interconnected, under both physiological and pathological conditions. Polycythemia vera (PV) is a myeloproliferative neoplasm (MPN) caused by a Janus kinase-2 (JAK2) mutation, resulting in uncontrolled red blood cell production and elevated hemoglobin and hematocrit levels. In PV, iron deficiency is common and may be due to several factors, including chronic gastrointestinal bleeding, chronic inflammation, dysregulated hepcidin signaling, and therapeutic phlebotomy. Many patients exhibit low serum ferritin and low to normal hepcidin levels despite erythroid proliferation, suggesting a maladaptive iron-restricted state. This functional iron deficiency may limit erythropoiesis to some extent, but also contributes to burdensome symptoms such as fatigue, cognitive impairment, and restless leg syndrome. Novel therapeutic approaches, including hepcidin mimetics or ferroportin inhibitors, aim to restore iron homeostasis, improving quality of life and potentially reducing the need for cytoreductive therapy (drugs used to treat MPNs by reducing blood cell production) in low-risk PV patients. In secondary forms of erythrocytosis (both congenital and acquired), iron homeostasis has been less often investigated. However, exploring it may be of great interest since in these affections, iron overload could act as a hidden driver of erythrocytosis by stimulating erythroblast proliferation. Hereditary hemochromatosis (HH) is a well-known cause of iron overload. While its association with erythrocytosis has been a subject of interest, it remains incompletely understood. In this review, we will explore the complex relationship between iron (deficiency or overload, including HH) and erythrocytosis (including PV), discussing underlying mechanisms and potential therapeutic applications.

Addition of Bruton's tyrosine kinase inhibitor (BTKi) to first-line (1 L) bendamustine-rituximab (BR) improved progression-free survival (PFS) in patients with mantle cell lymphoma (MCL) in the SHINE and ECHO trials. We investigated whether sequential treatment with 1 L BR and second-line (2 L) BTKi can result in similar cumulative PFS compared to BR-BTKi combination therapy, using a multicenter cohort of 755 patients treated with 1 L BR between 2014 and 2020. Event-free survival (EFS), EFS2, and overall survival (OS) were analyzed. By intention-to-treat (ITT), EFS2 was defined as time from 1 L BR start to progression/relapse or retreatment following 2 L BTKi or death. After a median follow-up of 61.4 (95% CI 56.4-65.9) months, the median EFS after 1 L BR was 34.2 (95% CI 31.5-38.4) months. The median EFS2 following 1 L BR and 2 L BTKi by ITT analysis was 64.8 (95% CI 56.7-82.8) months, and the 5-year OS rate after 1 L BR was 57.9% (95% CI 54.1-62.0%), close to SHINE and ECHO results. Patients without high-risk features (high simplified MIPI, high Ki-67, blastoid/pleomorphic morphology, TP53 mutation, or complex karyotype) had more favorable survival outcomes. These results suggest that sequential treatment with 1 L BR and 2 L BTKi remains reasonable for select patients with MCL, particularly those without high-risk features.

There is a clear link between type 2 diabetes mellitus (DM) and overall cancer risk. However, studies evaluating type 2 DM and multiple myeloma (MM) risk are limited, and the association is less clear. Understanding the impact of longstanding type 2 DM on organ systems and symptomatology in patients with a subsequent MM diagnosis, alongside potential overlapping toxicities from MM treatment, is crucial. This review summarizes the role of type 2 DM on MM risk and outcomes and explores the various mechanisms underlying these associations. A better understanding of this association will help improve outcomes in diabetic MM patients through lifestyle and drug related interventions. Clinical trial registration: Not applicable.

There is limited systemic data on the dynamics of BCMA-target antigen expression with BCMA CAR-T at relapse. We analyzed 76 patients receiving standard-of-care BCMA-directed CAR-T who underwent real-time BCMA expression evaluation at baseline (n = 50), relapse (6), or both (20) using flow cytometry (FC) and/or immunohistochemistry (IHC). BCMA was universally expressed at baseline with significant heterogeneity in expression level. No concordance was seen between FC and IHC in categorizing high vs. low expression (Spearman: 0.07, Cohen kappa: 0). Plasma cell BCMA expression by FC correlated with clinical outcomes, whereas IHC did not. High BCMA expression by FC was associated with increased likelihood for VGPR/CR (p = 0.007) and longer time to progression (p = 0.005), including the ciltacabtagene autoleucel cohort (median: 23.0 vs. 7.7 months, p = 0.02). Relapsed patients retained BCMA expression by FC, though 29% (5/16) had BCMA loss by IHC, with 4/5 showing concurrent positive BCMA expression by FC. BCMA expression at relapse by FC was significantly lower than baseline (p = 0.04); downregulation (≥25% decrease) occurred in 50% (8/16) with paired samples. Higher BCMA expression by FC correlated with higher likelihood of deep, durable responses following BCMA-directed CAR-T. While BCMA loss is rare, decreased expression is common at relapse, with implications for sequencing BCMA-directed therapies.

The CAR-HEMATOTOX (CAR-HT) score can assess hematotoxicity risk, but its utility in guiding supportive care remains underexplored. We analyzed 224 multiple myeloma patients treated with BCMA-directed CAR-T therapy (2016-2024), stratified by CAR-HT score (low <2 vs high ≥2). We evaluated the incidence and timing of early immune effector cell-associated hematotoxicity (ICAHT), other cytopenias, transfusion burden, cytopenia-directed interventions (growth factors and stem cell boosts), infections, and survival outcomes. High CAR-HT scores (58%) were associated with more grade 3 ICAHT (45.4% vs 23.3%) and grade 4 ICAHT (5.4% vs 1.2%; p = 0.0069), higher rates of grade ≥3 anemia (43.1% vs 24.4%, p < 0.0001) and thrombocytopenia (50.8% vs 27.9%, p < 0.0001). These patients were 7 times more likely to require red cell and platelet transfusions (p < 0.0001). G-CSF and TPO agonists were variably effective. Stem cell boosts (4%) led to rapid trilineage recovery. Infections occurred more frequently among high CAR-HT patients and those receiving intensive cytopenia-directed interventions. There were no significant differences in progression-free or overall survival between CAR-HT groups. Cytopenia-directed interventions did not affect survival. The CAR-HT score is a practical clinical risk tool that predicts transfusion burden and helps guide supportive care after BCMA CAR-T therapy.

Patients with peripheral T cell lymphoma (PTCL) who achieved tumor response with first-line standard therapy were at high risk of disease relapse. We explored golidocitinib (150 mg once daily) as maintenance therapy for this group of patients (JACKPOT26, NCT06511869). This study included two cohorts: patients achieving a complete response (Cohort 1 (CR), N = 30) and a partial response (Cohort 2 (PR), N = 18) during induction stage. All enrolled patients were transplant ineligible or did not have a transplant plan. All dosed patients were included in the efficacy and safety analysis. In Cohort 1, the 24-month disease free survival (DFS) rate was 74.2% with golidocitinib treatment. In nodal subtypes (AITL, NOS, ALK- ALCL), the 24-month DFS rate was 62.7%. In Cohort 2, median progression free survival (PFS) was 17.4 months, and 24-month PFS rate was 48.6%. Nine out of 18 patients with initial PR achieved complete response, leading to a complete response rate of 50.0%, and median duration of response of 23.9 months. The most common ≥grade 3 treatment-related treatment-emergent adverse events (TRAEs) were hematological adverse events in nature, including neutrophil count decreased (47.9%), white blood cell count decreased (31.3%), lymphocyte count decreased (14.6%) and leukopenia (12.5%). The majority of these TRAEs were reversible and clinically manageable. TRAEs leading to treatment interruption and discontinuation occurred in 60.4% and 10% of patients, respectively. No TRAEs leading to fatal outcomes were reported. This study suggests the potential of golidocitinib as maintenance therapy for patients with PTCL.

Genome-wide association studies (GWAS) have identified germline genetic variants for follicular lymphoma (FL) susceptibility. We conducted a GWAS of prognosis in FL patients to identify genetic predictors of event-free survival (EFS) as well as failure within the first 24 months after treatment initiation (EFS24) using patients treated with rituximab-based immunochemotherapy from three clinical trials and one prospective observational study (N = 1054). Statistical approaches consisted of a pooled GWAS of the four cohorts and a leave-one-cohort-out (LOCO) strategy to identify robust findings that replicated across the four cohorts. The top SNPs for EFS and EFS24 were marked by rs72625024 at 3q27.3 near FETUB and HRG (P = 9.37 × 10-8) and rs114695031 at 14q32.13 near TCL6 (P = 1.93 × 10-8), respectively. These two loci, which were discovered and validated in all 4 LOCO rounds, map near long-non-coding RNAs with putative tumor suppressor functions. Our results pinpoint potential novel biology and the contribution of host genetics to prognosis in FL.