Introduction Testicular plasmacytoma (TP) is a rare manifestation of plasma cell neoplasms (PCNs), with limited data regarding its presentation, management, and prognosis. We evaluated the clinicopathologic characteristics, treatment, and survival outcomes of TP in the largest single-institution cohort to date, supplemented by a contemporary literature review. Materials and Methods We retrospectively reviewed 26,523 patients with PCNs treated between 2000 and 2025. Patients with TP confirmed by imaging, biopsy, or orchiectomy were included. A focused literature review of TP published during the same period was performed. Demographic, clinicopathologic, treatment, and survival outcomes were analyzed. Results In our institutional cohort, 17 of 759 patients (2.2%) with extramedullary disease (EMD) had testicular involvement; no cases of solitary TP were identified. Median age at TP diagnosis was 58 years, and 82% had relapsed or refractory MM. IgG and IgA were the predominant immunoglobulin subtypes (50% each). High-risk histopathologic features, including plasmablastic morphology and c-MYC expression, were identified in a small subset of patients. Systemic anti-myeloma therapy following TP diagnosis was documented in 59% of patients, and 71% underwent autologous stem cell transplantation. Concurrent bone marrow involvement was present in 35% and was associated with significantly shorter overall survival (median overall survival, 6 vs 55 months; log-rank p= 0.002). Median progression-free and overall survival from TP diagnosis for the overall cohort were 6 and 36 months, respectively. The literature review also identified 35 TP cases, including 6 solitary TP and 29 cases associated with multiple myeloma (MM). Solitary TP demonstrated favorable outcomes following orchiectomy. Conclusions TP comprises two clinically distinct entities. Solitary TP has been associated with favorable short-term outcomes after orchiectomy alone. In contrast, TP associated with MM carries poor outcomes, particularly with concurrent bone marrow involvement, and requires early systemic therapy and multidisciplinary management.
Background Mogamulizumab is an established treatment option for relapsed/refractory mycosis fungoides (MF) and Sézary syndrome (SS); however, large-scale real-world outcome data remain limited. Methods We conducted a retrospective cohort study on patients with MF or SS who received treatment with mogamulizumab using TriNetX. Results A total of 394 patients were included [182 (46.2%) MF, 212 (53.8%) SS]. The median follow-up was 31.5 months. The 1- and 3-year OS rates were 85.7% and 73.4%, respectively. Corresponding rates among MF and SS patients were 82.0% versus 88.2% and 69.3% versus 76.7%. In univariable analyses, SS was associated with improved OS (HR 0.75, 95% CI 0.57–0.98; p=0.032), whereas nodal involvement predicted inferior survival (HR 1.36, 95% CI 1.01–1.93; p=0.043). Following adjustment, both associations were attenuated to non-significant trends (SS: aHR=0.70, p=0.067; nodal involvement: aHR 1.40, 95% CI 0.95–2.06; p=0.089). Overall, 154 patients (39.1%) required subsequent systemic therapy, with the 1- and 3-year cumulative incidence being 31.1% (95% CI: 25.7-35.7%) and 41.0% (95% CI: 35.1-46.9%), respectively. Elevated LDH independently predicted shorter TTNT (acsHR 1.62, 95% CI 1.29–2.03; p<0.001). The 12-month incidences of infection, sepsis, hospitalization, and emergency department visits were 39.8%, 13.5%, 34.3%, and 20.6%, respectively, with similar incidences between MF and SS. Conclusions In this large real-world cohort, mogamulizumab was associated with durable survival, prolonged treatment-free intervals, and the outcomes observed were consistent with the pattern seen in the MAVORIC trial. Micro-Abstract Real-world evidence on mogamulizumab for mycosis fungoides (MF) and Sézary syndrome (SS) remains limited. We conducted a retrospective analysis of 394 patients with MF/SS treated with mogamulizumab within TriNetX. Three-year OS was 73.4%, while the 3-year cumulative incidence of subsequent systemic therapy was 41.0%. Twenty-five (16.2%) patients proceeded to stem cell transplant; the median interval from last mogamulizumab dose was 314 days, with a 48.0% incidence of any-grade graft-versus-host disease. Elevated lactate dehydrogenase independently predicted earlier treatment transition. Overall, mogamulizumab provides favorable real-world outcomes and durable clinical benefit in patients with MF and SS.
INTRODUCTION/BACKGROUND:T-cell-engaging bispecific antibodies (BsAbs) are effective for relapsed/refractory (R/R) B-cell non-Hodgkin lymphomas (B-NHLs). Radiation therapy (RT) is increasingly used for palliation or bridging/cytoreduction in patients receiving BsAbs, but data on the safety of RT delivered in close temporal proximity to BsAbs are limited. We report the largest series to date evaluating RT and BsAbs in B-NHL. PATIENTS AND METHODS:We retrospectively identified patients with B-NHL who received RT ≤ 3 months before, during, or ≤ 3 months after BsAb at a single institution between 2018 and 2024. Timing was categorized as pre-, peri-, or post-BsAb. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded per ASTCT criteria; other toxicities per CTCAE v5.0. In-field responses were assessed per Lugano criteria. RESULTS:Twenty-nine patients underwent 31 BsAb courses and received RT to 52 sites (50% pre-, 13% peri-, 37% post-BsAb). Common histologies included DLBCL (52%), follicular lymphoma (FL) (26%), and transformed FL (16%). All RT-related toxicities were grade 1 to 2, with no RT-related hospitalizations. CRS occurred in 7 BsAb courses and ICANS in 4, with no apparent relationship to RT timing or dose. Early post-RT lymphopenia was common across groups, but its frequency and severity did not differ by RT timing. Among 44 evaluable lesions, the in-field overall response rate was 84% (CR 45%, PR 39%). CONCLUSION:RT before, during, or after BsAb was well tolerated, without apparent additive toxicity, and achieved high in-field response rates, supporting the safe integration of RT with BsAbs for R/R B-NHL.
The treatment landscape of multiple myeloma (MM) is evolving rapidly, driven by the approval of new therapies and the increasing integration of advanced response-assessment tools, including measurable residual disease (MRD). These developments have made treatment algorithms increasingly complex. Furthermore, access to novel therapies is often delayed and varies from one country to another, necessitating national-level treatment guidelines. Under the auspices of the Turkish Society of Hematology, we have been publishing national treatment guidelines. The first national myeloma guideline was published in 2020 and subsequently updated in 2024. Building on recently published registrational data and the 2025 EHA–EMN guidelines, we present the second update of the Turkish Myeloma Treatment Guidelines.We aim to include all currently approved therapies as well as emerging therapies likely to be approved in the near future. This approach guides Turkish hematologists in daily routine practice when needed. This guidance aligns with internationally accepted standards and explicitly considers reimbursement protocols and their impact on local implementation. This effort aims to support new drug approvals and facilitate the implementation of diagnostic and response-assessment tools in routine clinical practice in Türkiye. Our objective is to promote consistent, equitable, and adaptable myeloma care across Türkiye.
BACKGROUND:Chimeric antigen receptor (CAR) T-cell therapies offer substantial survival benefits for relapsed and/or refractory multiple myeloma (RRMM). However, access remains limited across the US. We examined geographic variation in MM burden and key drivers of CAR T access disparities to inform targeted strategies to close these gaps. PATIENTS AND METHODS:Patients with MM and CAR T recipients from January 2021-August 2024 were identified from the Komodo Patient-Level Analytics and Insights Derivative claims database. MM prevalence at the ZIP-3 level came from the US Cancer Statistics database. Drive-times to the nearest authorized treatment center (ATC) for patients with MM and to ATCs for CAR T recipients were calculated and compared nationally and by region. RESULTS:There were 106,593 prevalent patients over the study period. The South had the second highest MM burden (66.1/100,000 people) but the lowest proportion of patients within 1 hour of an ATC (55.7%). CAR T recipients in the South also traveled the longest to their ATC (median, 1.5 hours). Multivariable analysis with socio-economic and demographic covariates indicated that ≥ 2 hour potential drive-time to nearest ATC versus < 1 hour (adjusted odds ratio [or] = 0.43; 95% confidence interval (CI), 0.27-0.69), household income < $50k versus ≥ $100k (or = 0.19; 95% CI, 0.05-0.69), and residence in nonmetropolitan areas versus metropolitan (or = 0.41; 95% CI, 0.28-0.60) were significantly associated with reduced odds of CAR T use. CONCLUSIONS:There were substantial geographic and socioeconomic disparities in CAR T access, with long drive‑times, lower household income, and non‑metro residence limiting uptake and underscoring the need for targeted ATC expansion.
INTRODUCTION:Azacitidine-venetoclax (AZA-VEN) has become a standard treatment in older or chemotherapy-ineligible AML patients. While the registration trial showed a median overall survival (OS) of 14.7 months, most real-world studies have not reproduced this result. PATIENTS AND METHODS:We analyzed treatment patterns, adverse events, responses and outcomes in 199 patients treated with AZA-VEN in the DATAML registry. RESULTS:The median age was 75.6 years, 48.7% had secondary AML (11% post-MPN); 11.7% had another cancer, and 9% had received AZA for prior myelodysplastic syndrome. Cytogenetic risk was intermediate (55.8%) or adverse (43.7%). The most frequent gene mutations were ASXL1 (33%), TET2 (27%), TP53 (26%), RUNX1 (24%) and SRSF2 (24%). The first cycle was performed on an outpatient basis in 39.4% of patients. The median number of cycles was 4 and 37% received > 6 cycles. Beyond cycle 6, reductions in treatment dose or duration were attributed to VEN in 55% of patients and to AZA for 43%. The complete remission (CR) plus CR with incomplete hematologic recovery (CRi) rate was 58.5%, and day-30 death rate was 3%. Median OS was 8.9 months. mPRS and refined-ELN2024 classifications were significantly associated with response and OS. In CR/CRi patients, G-CSF use was significantly and independently associated with improved OS (median, 10.1 months without versus 20.3 with G-CSF; P = .001). In an external cohort, G-CSF was also associated with a trend towards improved OS. CONCLUSION:In real-world clinical practice, patients with more severe characteristics are typically selected for AZA-VEN, which could explain suboptimal outcomes. G-CSF should be prospectively explored in AZA-VEN treated patients.
Myelofibrosis (MF) is a biologically heterogeneous myeloproliferative neoplasm characterized by constitutive activation of the JAK-STAT pathway, progressive marrow fibrosis, cytopenias, splenomegaly, and systemic inflammation. Ruxolitinib, a JAK1/JAK2 inhibitor, remains the standard frontline therapy for intermediate- and high-risk MF, providing significant improvements in splenomegaly, constitutional symptoms, and survival. However, responses are highly variable, and a substantial proportion of patients experience suboptimal benefit, early discontinuation, or disease progression, underscoring the need for reliable predictors of treatment outcome. This review summarizes current evidence on clinical, molecular, cytogenetic, and dynamic predictors of ruxolitinib response in MF. Clinical variables, including cytopenic phenotype, peripheral blasts, baseline spleen size, symptom burden, prognostic risk category, timing of treatment initiation, and dose intensity, consistently influence treatment efficacy and durability. Notably, inadequate dose intensity emerges as the most relevant modifiable determinant of response. Molecular profiling further refines risk stratification: high-molecular-risk mutations, increased mutational burden, RAS/CBL pathway alterations, and adverse cytogenetics are associated with inferior outcomes, while driver mutation status alone has limited predictive value. The emergence of dynamic prognostic models such as RR6, iRR6, and STR-PM has enabled the integration of early treatment-related variables, including spleen response, transfusion dependence, and dose intensity, to identify patients at higher risk of treatment failure. These tools represent a shift from static baseline prognostication toward adaptive, response-oriented management. Emerging approaches integrating multi-omics profiling, circulating biomarkers, and artificial intelligence are warranted to further improve individualized decision-making among the expanding JAK inhibitor-based strategies in MF.
Mediastinal gray zone lymphoma (MGZL) is a very rare aggressive B-cell non-Hodgkin lymphoma characterized by clinical, pathologic, and molecular features that overlap between nodular sclerosis Hodgkin lymphoma (NSHL) and primary mediastinal B-cell lymphoma (PMBL). While these are clinically related lymphomas, recent molecular profiling studies demonstrated similarities between these 3 entities, including alterations in the nuclear factor-κB pathway, JAK2/STAT signaling, copy number alterations in 9p24.1, and immune evasion. In the most recent WHO-5 and ICC classifications, the definition of GZL was restricted to mediastinal GZL (MGZL), which remains as a separate entity between NSHL and PMBL; however, non-mediastinal GZL was classified under diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS). Given the rarity of the disease, evolving definition, and diagnostic challenges, few prospective studies have been undertaken to evaluate treatment outcomes. Response rates and survival with frontline chemotherapy are inferior compared to PMBL, and retrospective studies suggest superiority of dose-intensive regimens compared to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in MGZL. Despite recent therapeutic advancements in PMBL and classical Hodgkin lymphoma (cHL), most clinical trials have excluded patients with MGZL, leading to uncertainty regarding the best therapeutic strategy in both the frontline and relapsed/refractory settings.
Chronic myeloid leukemia (CML) is a leading example of how targeted therapy can transform cancer outcomes. Since the introduction of tyrosine kinase inhibitors (TKIs), survival in high-income countries has approached that of the general population. Large-scale access initiatives have demonstrated that sustained delivery of TKIs is also feasible in low- and middle-income countries (LMICs), with comparable outcomes, challenging assumptions about the limits of cancer care in resource-constrained settings.As treatment access has expanded in LMICs, the central challenge in CML care has shifted to delivery of optimized, sustainable care. Achieving optimal outcomes requires timely diagnosis, sustained adherence, regular molecular monitoring, and the ability to adjust treatment based on individual patients’ tolerance and response to therapy. However, gaps in diagnostic capacity, lack of coordination in care delivery, and persistent socioeconomic barriers continue to limit continuity of care and constrain the full benefits of therapy.Here we review the evidence on the evolving landscape of CML care in LMICs, including treatment access, molecular monitoring, adherence, and treatment-free remission (TFR). Molecular monitoring represents the critical bottleneck linking treatment access to optimized care and long-term outcomes, requiring innovative tools and approaches to scale up access to molecular diagnostics in resource-limited settings.Advancing equitable outcomes in CML will require multiple partners, including industry, government, academia, and non-profit entities. Access barriers for CML are a global concern, and lessons learned in addressing these challenges in LMICs may inform program strategies in other contexts, including marginalized communities in high-income countries.
INTRODUCTION:Growing data support interactions between host-gut microbes and treatment responses in multiple myeloma (MM), where a higher abundance of Eubacterium hallii in stool samples has been found among MM patients with negative minimal residual disease after induction therapy. Here, we evaluated changes in the gut microbiome associated with daratumumab (dara) based therapy in 40 MM patients, before and after therapy. PATIENTS AND METHODS:Patients with relapsed MM and prior autologous transplantation who had received 1 to 4 prior lines of therapy were eligible. Two stool samples were collected, one within 1 week prior to dara (predara) and one immediately after 4 doses of dara (postdara). Metagenomics sequencing was conducted. Microbiome taxonomic analyses were performed using MetaPhlAn4, and microbial functional pathway analyses were conducted using HUMAnN3.6. QIIME2 was used for compositional and statistical analyses. RESULTS:Of 40 participants enrolled, there were 5 nonresponders; 35 patients achieved partial response (PR) or better (responders). Among responders, 10 patients achieved complete remission (CR), and 25 patients achieved either very good partial response (VGPR) or PR. There were no statistically significant differences between overall pre and postdara gut microbiomes. Differential abundance analysis (ANCOM-BC) showed statistically significant (q ≤ 0.05) overgrowth of Alistipes finegoldii and Acidaminococcus intestini species in responders and Ruminococcus torques, Sellimonas intestinalis and Clostridium symbiosum in nonresponders. Compared to non-CR, CR samples showed enrichment of Faecalibacterium prausnitzii; non-CR samples were enriched in Segatella copri and Faecalimonas umbilicata. DISCUSSION/CONCLUSION:Our results suggest differences in species between clinical responders and nonresponders, but larger prospective studies are needed to confirm these results.
Menin inhibitors (MIs) represent a novel class of targeted agents that disrupt the interaction between the nuclear protein menin and the KMT2A (MLL) complex, thereby interrupting a crucial oncogenic transcriptional program in acute myeloid leukemias (AML) with KMT2A rearrangements and NPM1 mutations. Robust preclinical data have shown that menin inhibition suppresses HOXA/MEIS1 expression, induces differentiation, and reduces the fitness of leukemic cells, including the stem-like compartment. These findings rapidly led to phase I/II clinical trials with oral MIs such as revumenib and ziftomenib, which demonstrated CR+CRh rates of 22% to 23% in refractory/relapsed patients, with conversion to measurable residual disease (MRD) negativity in 61% to 68% of responders and early use as a bridge to allogeneic transplantation. However, the median duration of response remains limited (approximately 4-5 months), suggesting that menin inhibition as monotherapy may be insufficient to ensure durable disease control. Key emerging clinical issues include specific adverse events (QTc prolongation in 12%-44%, differentiation syndrome in 10%-29%), drug-drug interactions mediated by CYP3A4 metabolism, resistance dynamics (on-target mutations in 39% of cases), and the definition of the optimal role in combination with venetoclax, hypomethylating agents, and intensive chemotherapy. This review synthesizes molecular mechanisms, preclinical and clinical data, discusses use within MRD-guided and transplant pathways, and proposes translational priorities for integrating MIs into future therapeutic paradigms, pending confirmation from randomized studies.
Dasatinib 100 mg once daily is effective for chronic-phase chronic myeloid leukemia (CP-CML), but dose-related toxicity may limit long-term tolerability. We therefore evaluated whether dasatinib 50 mg once daily as an initial dose strategy preserves efficacy while improving safety compared with 100 mg once daily. We performed a systematic review and meta-analysis of adults with CP-CML treated with initial dasatinib 50 mg once daily. MEDLINE via PubMed, Embase, Cochrane CENTRAL, and Web of Science were searched from inception to March 15, 2026. Direct comparative studies of dasatinib 50 mg versus 100 mg were included in the primary analysis; whereas single-arm 50 mg cohorts were summarized as supportive evidence. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using random-effects models. Among 613 records identified, 10 reports met eligibility criteria and 7 nonoverlapping analytic reports were retained. Two studies directly compared frontline dasatinib 50 mg versus 100 mg. Twelve-month major molecular response was similar between doses (RR 1.07, 95% CI, 0.92-1.24), while complete cytogenetic response favored 50 mg in unadjusted analysis (RR 1.09, 95% CI, 1.02-1.16). Dasatinib 50 mg reduced pleural effusion (RR 0.20, 95% CI, 0.08-0.50) and thrombocytopenia (RR 0.71, 95% CI, 0.52-0.96). Supportive frontline single-arm data showed pooled 12-month MMR and CCyR proportions of 70.6% and 95.0%, respectively.Overall, initial dasatinib 50 mg once daily may preserve key efficacy outcomes while improving tolerability in CP-CML. Prospective controlled studies are needed.
Background The CAR-HEMATOTOX score has been associated with hematologic toxicity after chimeric antigen receptor T-cell therapy, but it is usually assessed shortly before lymphodepletion, when hematopoietic reserve may already be affected by bridging therapy. We investigated whether the CAR-HEMATOTOX score assessed at leukapheresis, before bridging therapy initiation (Pre-CAR-HEMATOTOX), could predict delayed platelet recovery after idecabtagene vicleucel (ide-cel) in relapsed/refractory multiple myeloma. Patients and Methods We conducted a single-center retrospective cohort study of consecutive patients with relapsed/refractory multiple myeloma who underwent leukapheresis and subsequently received ide-cel between November 2022 and March 2026. The primary endpoint was time to platelet recovery to ≥ 100 × 109/L without platelet transfusion or thrombopoietin receptor agonist support. Secondary endpoints included time to platelet recovery to ≥ 75 × 109/L, time to neutrophil recovery to ≥ 1.0 × 109/L without granulocyte colony-stimulating factor support, and platelet transfusion burden. Results Among 96 patients, median time to platelet recovery to ≥ 100 × 109/L was significantly shorter in the Pre-CAR-HEMATOTOX low group than in the high group (1.8 vs. 15.8 months, P < .001). Similar findings were observed for recovery to ≥ 75 × 109/L (1.3 vs. 6.3 months, P = .005). High Pre-CAR-HEMATOTOX remained independently associated with delayed platelet recovery in both the primary and exploratory multivariable models. High Pre-CAR-HEMATOTOX was also associated with greater platelet transfusion burden. In contrast, intensive BT, rather than Pre-CAR-HEMATOTOX, was independently associated with delayed neutrophil recovery. Conclusions Pre-CAR-HEMATOTOX assessed at leukapheresis predicted delayed platelet recovery after ide-cel and may support early risk stratification before BT selection.
PURPOSE:BCMA-directed bispecific antibodies (BsAbs) have improved outcomes in relapsed/refractory multiple myeloma (rrMM), but early toxicities often require close hospital monitoring. We evaluated the feasibility and safety of BsAb administration through a Hospital at Home (HaH) model. PATIENTS AND METHODS:We conducted a retrospective multicenter real-world study including consecutive triple-class or penta-refractory rrMM patients treated with teclistamab or elranatamab between July 2022 and January 2024. Outcomes of patients receiving at least one HaH administration were descriptively evaluated alongside those of patients managed exclusively in conventional hospital settings. Safety and survival outcomes were assessed using a 68-day landmark analysis corresponding to the median time to HaH transition. RESULTS:Among 201 patients, 46 received HaH administration and 155 were managed exclusively in hospital. Baseline characteristics were broadly comparable, with differences consistent with clinical selection for HaH, notably performance status. After the landmark, no grade ≥ 3 infection was observed in the HaH group, whereas severe infectious events continued to accumulate in the No HaH group. Rates of post-landmark bacterial, respiratory, opportunistic, and fungal infections were broadly similar across care pathways. Overall survival, progression-free survival, and time to treatment failure did not suggest inferior outcomes in the HaH group. CONCLUSION:In selected rrMM patients, HaH administration of BsAb therapy was feasible and was not associated with inferior survival outcomes. The lower observed rate of severe infections supports further evaluation of this model, while accounting for clinical selection and supportive-care differences.
BACKGROUND:The prognostic significance of the proportion of normal metaphases detected at diagnosis in acute myeloid leukemia (AML) has not been systematically evaluated. PATIENTS AND METHODS:We conducted a retrospective cohort study of 893 adult AML patients treated at Cleveland Clinic between January 2015 and September 2023 who underwent conventional cytogenetic analysis. Normal karyotype fraction (NKF) was defined as the proportion of normal metaphases among all metaphases analyzed at diagnosis. NKF was evaluated as a continuous measure and categorized using three-group (NKF = 0, 0 < NKF < 1, NKF = 1) and 5-group functional classification systems. Primary outcomes included overall survival (OS), event-free survival (EFS), composite complete remission (CR/CRi), and relapse. Multivariable Cox proportional hazards and logistic regression models were adjusted for established prognostic covariates. RESULTS:NKF demonstrated a bimodal distribution across the cohort. Patients with NKF = 1 achieved the highest CR/CRi rate (64%) and longest median OS (16 months) and EFS (11 months). In multivariable analyses, NKF = 1 was independently associated with improved OS (hazard ratio [HR], 0.77, 95% confidence interval [CI], 0.61-0.97) and EFS (HR, 0.73, 95% CI, 0.58-0.91), and higher odds of achieving CR/CRi (odds ratio 1.72, 95% CI, 1.10-2.70) compared with NKF = 0. EFS was significantly associated with NKF categories in both classification systems (P < .05). CONCLUSION:NKF is a readily obtainable cytogenetic parameter that was associated with treatment response and survival in this cohort. External validation and prospective studies are warranted to support its use in clinical risk stratification frameworks.
