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In this prospective study involving 37 Duchenne muscular dystrophy (DMD) patients aged 8–18 years and older, we examined the impact of neurological and cardiac factors on quality of life (QoL). Our findings revealed a negative correlation between upper limb movement and overall mobility, self-service, and usual activities. Ambulatory and non-ambulatory DMD patients showed significant differences in mobility-related parameters. Cardiac evaluations demonstrated associations between mitral annular plane systolic excursion (MAPSE) and mobility-related aspects. The PEDSQL 3.0 neuromuscular model questionnaire further highlighted age-related and movement-related correlations with QoL. The loss of ambulatory status and reduced upper limb movement were negatively associated with QoL, while upper limb movement positively correlated with septal MAPSE. However, no significant associations were found between MAPSE and anxiety/depression. These findings underscore the multifaceted impact of DMD on QoL and emphasize the importance of considering both neurological and cardiac factors in comprehensive patient care. [ABSTRACT FROM AUTHOR]

Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): 1. European Regional Development Fund - Project ENOCH (No. CZ.02.1.01/0.0/0.0/16_019/0000868) 2. Specific University Research provided by MŠMT, No.: MUNI/A/1462/2021 Background Cardiac magnetic resonance feature tracking (CMR-FT) allows a quantitative analysis of regional heart deformation and understanding several diseases' underlying mechanisms. Paroxysmal atrial fibrillation (PAF), defined as recurrent arrhythmic episodes that terminate spontaneously, may induce early changes in the left atrial (LA) wall, which CMR-FT can detect. Thus, the LA function assessment may help early identification of PAF via imaging markers. Purpose Evaluate the left atrial volumetric change rate in PAF patients during the reservoir and contractile LA phases. Methods The local Ethics Committee approved the study following the Declaration of Helsinki (2000) of the World Medical Association. A group of 50 subjects (27 PAF patients and 23 controls (CG)) were examined with CMR. The analyses were performed using CMR-FT commercial software (2D CPA MR, TomTec v4.6.4.40, Germany). Left ventricle (LV) and left atrial (LA) volume curves were obtained from analyzing long-axis cine images (50 frames per cardiac cycle). Corresponding slopes in the reservoir-LV emptying (LVemp) and LA filling (LAfill) volume rate-and contractile-LV filling (LVfill) and LA emptying (LAemp) volume rate-phases were calculated. Negative slope values imply blood volume decreasing with time. The LA longitudinal strain (LS) was also assessed. All statistical data analyses were done in RStudio (R, v4.0.3). Results PAF patients have a significatively higher LAfill and lower LAemp than controls in the reservoir and contractile phases (LAfill 129.1±32.6 ml/s vs 101.4±22.8 ml/s, P<0.001 and LAemp -154.1±54.0 ml/s  vs -116.2±40.4 ml/s, P=0.007). In contrast, the LV volumetric rates were similar in both phases (LVemp -311.3±79.2 ml/s vs -280.3±62.1 ml/s, P=0.128 and LVfill 199.4±75.6 ml/s vs 190.0±62.8 ml/s, P=0.631, respectively). The volumetric rates significantly correlated for PAF patients (reservoir (LVemp and LAfill) r = -0.54, P = 0.003 and contractile (LVfill and LAemp) r = -0.64, P < 0.001), but not for controls. The LS was also impaired in PAF patients vs controls (reservoir 26.1% (21.5% to 30.5%) vs 32.7% (28.1% to 39.1%), P = 0.001 and contractile 10.5% (8.8% to 13.3%) vs 14.9% (12.1% to 19.7%), P = 0.003). Conclusion The LA volumetric rates suggest a possible compensation mechanism that allows the LA to deform faster or slower enough to receive or release blood volume during the LA phases; PAF patients' LA receives more blood in a fixed time interval. Their LA cavity could experience pressure or volume overload, allowing LA enlargement. Likewise, the LA emptying (contractile) was slower in PAF patients, which means they release less blood than controls in a given time. Consequently, the PAF patient's LA holds a higher blood volume during the whole cardiac cycle. However, other explanatory factors should be independently assessed. The volumetric rates assessment through CMR-FT could help identify early changes in the LA deformation in PAF patients. [ABSTRACT FROM AUTHOR]

Abstract: Rising blast percentage or secondary acute myeloid leukemia (sAML) transformation in myeloproliferative neoplasms (MPNs) leads to JAK1/2 inhibitor (JAKi) therapy resistance and poor survival. Here, we demonstrate that treatment with the CDK7 inhibitor (CDK7i) SY-5609 depletes phenotypically characterized post-MPN sAML stem/progenitor cells. In cultured post-MPN sAML SET2, HEL and patient-derived (PD) post-MPN sAML cells, SY-5609 treatment inhibited growth and induced lethality while sparing normal cells. RNA-sequencing analysis after SY-5609 treatment reduced mRNA expression of MYC, MYB, CDK4/6, PIM1, and CCND1 but increased expression of CDKN1A and BCL2L1. Mass spectrometry of SY-5609-treated MPN-sAML cells also reduced c-Myc, c-Myb, PIM1, and CDK4/6 but increased p21, caspase-9, and BAD protein levels. CRISPR-mediated CDK7 depletion also reduced cell viability of HEL cells. Cytometry by time of flight (CyTOF) analysis of SY-5609-treated PD post-MPN sAML stem/progenitor cells showed reduced c-Myc, CDK6, and PU.1 but increased protein levels of CD11b, p21, and cleaved caspase-3. Cotreatment with SY-5609 and ruxolitinib was synergistically lethal in HEL, SET2, and PD post-MPN sAML cells. A CRISPR screen in sAML cells revealed BRD4, CBP, and p300 as codependencies with CDK7i. Accordingly, cotreatment with SY-5609 and the bromodomain and extra-terminal protein inhibitor (BETi) OTX015 or pelabresib or the CBP/p300 inhibitor GNE-049 was synergistically lethal in MPN-sAML cells (including those exhibiting TP53 loss). Finally, in the HEL-Luc/GFP xenograft model, compared with each agent alone, cotreatment with SY-5609 and OTX015 reduced sAML burden and improved survival without host toxicity. These findings demonstrate promising preclinical activity of CDK7i-based combinations with BETi or CBP/p300 inhibitor against advanced MPNs, including post-MPN sAML., (© 2025 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: The MD Anderson Institutional Review Board approved this study. All patients provided written informed consent according to the Declaration of Helsinki.

Competing Interests: Competing interests: ATK had a consultancy with GSK, CTI Biopharma, Imago Biosciences, received honoraria from Incyte, MorphoSys, BMS, received travel support from Abbvie and MorphoSys, and participated on a Data Safety Monitoring Board or Advisory Board for Incyte. DAS had a consultancy with Abbvie, Gilead, Agios, Celyad, Foghorn, Incyte, Intellisphere, Kite, Magenta, Novartis, Affimed, Molecular Partners, PGEN Therapeutics, Takeda, and Zentalis. DAS served on the advisory board for Syros, Shattuck Labs, Jasper Therapeutics, Dark Blue Therapeutics, BMS, Syndax, Servier, Rigel Pharmaceuticals, AvenCell, Kite, Magenta, Novartis, Astellas, BlueBird Bio, Intellia, BMS, and Nkarta. DAS received research funding from Jazz Pharmaceuticals. MP had a consultancy with received honoraria from ION Pharma, Jansen Oncology, Olema Pharmaceuticals, Daiichi Sankyo, Kura Oncology, Accutar Biotech, and Nurix. AP received research funding from Monte Rosa Therapeutics, Frontier Med, Valerio, Abbvie, Immuneering, and Arvinas. LM participated on the advisory board for MorphoSys. GK received honoraria from Astellas and research funding from Prelude, Sumitomo Pharam, Schrodinger, Cyteir, and Abbvie. AV is a current equity holder in Stelexis, Clinstreet, and Bioconvergent health. AV received research funding from Prelude, BMS, Curis, and Halia. AV is a member of the board of directors or advisory committee of Stelexis, Curis and Calico. NB, MW, JR, AM, DH, SR, and WJH are current employees and equity holders of Prelude Therapeutics. OA-W is a founder and scientific advisor of Codify Therapeutics, holds equity in this company, and receives research funding from this company. OA-W has served as a consultant for Foundation Medicine Inc., Merck, Prelude Therapeutics, Amphista Therapeutics, MagnetBio, and Janssen, and is on the Scientific Advisory Board of Envisagenics Inc., Harmonic Discovery Inc., and Pfizer Boulder; OA-W has received prior research funding from H3B Biomedicine, Nurix Therapeutics, Minovia Therapeutics, and LOXO Oncology unrelated to the current manuscript. EMS received research funding from Bayer; was a consultant for Amgen, AbbVie, Seattle Genetics, and Biotheryx; served as a consultant and received research funding from Syndax; was a member of the Board of Directors or advisory committee for PTC Therapeutics and Syros; served as a consultant and was member of the Board of Directors or advisory committee for Astellas Pharmaceutical, Agios Pharmaceuticals, and Genentech; served as a consultant, received research funding, and was a member of the Board of Directors or advisory committee for Daiichi-Sankyo, Celgene Pharmaceuticals, and Novartis; and is a current equity holder in privately held Auron Therapeutics. All other authors have no conflicts of interest to declare. All conflicts of interest declared are unrelated to the content of this manuscript. Ethics approval and consent to participate: All methods were performed in accordance with the relevant guidelines and regulations. The study was approved by the review boards at the participating institutions. The names of these boards can be found in Supplementary Table 9. All patients provided written informed consent prior to enrollment in the study.

Background: All-trans retinoic acid (ATRA) and arsenic trioxide (ATO) combinations have produced excellent outcomes in patients with standard-risk acute promyelocytic leukemia (APL). Herein, the authors update their long-term results with the regimen of ATO-ATRA and gemtuzumab ozogamicin (GO) in standard-risk and high-risk APL., Methods: This was a phase 2 trial of patients with newly diagnosed APL. Induction comprised ATRA 45 mg/m 2 and ATO 0.15 mg/kg daily. GO 6-9 mg/m 2 was added for high-risk patients and for standard-risk patients who developed leukocytosis >10 × 10 9 /L. Consolidation consisted of four courses of ATO-ATRA, with GO for patients who had PML::RARA persistence., Results: One hundred forty-six patients (median age, 53.0 years; range, 19.3-83.9 years) were treated, including 106 patients (72.6%) with standard-risk APL and 40 (27.4%) with high-risk APL. GO was administered to 68 standard-risk patients (64.2%) for leukocytosis. The complete remission rate was 93.8% (95% confidence interval [CI], 92.2%-98.5%). Negative measurable residual disease status was achieved in 97.1% of patients who attained complete remission. At a median follow-up of 61.8 months (95% CI, 4.7-128.4 months), the 5-year event-free survival, disease-free survival, and overall survival rates were 92.4% (95% CI, 87.9%-97.1%), 93.6% (95% CI, 89.5%-97.8%), and 93.1% (95% CI, 88.9%-97.7%), respectively. Induction mortality was 2.7%. The most common severe adverse events were elevated transaminases in 41.0% of patients and infection in 13.7%. There were no cases of veno-occlusive disease., Conclusions: The combination of ATO-ATRA and GO was curative in 94% of patients who had APL with a favorable safety profile (ClinicalTrials.gov identifier NCT01409161)., (© 2024 American Cancer Society.)

The oral Janus kinase (JAK) 1/JAK2 inhibitor ruxolitinib was approved by the US Food and Drug Administration in 2014 for treatment of patients with polycythemia vera (PV) who have an inadequate response to or intolerance of hydroxyurea (HU). PV is a chronic myeloproliferative neoplasm defined by primary absolute erythrocytosis, bone marrow hypercellularity, and JAK mutations such as JAK2V617F. Patients with PV experience burdensome symptoms and are at risk of thromboembolic events, in particular those with resistance to or intolerance of initial treatments such as HU. Other risks for patients with PV include progression of disease to more aggressive forms with worse prognoses, such as myelofibrosis or blast-phase myeloproliferative neoplasms. This review summarizes the efficacy and safety of ruxolitinib from key phase 2 and 3 trials (MAJIC-PV, RESPONSE, RESPONSE-2, RELIEF, and Ruxo-BEAT), large real-world studies, and a decade of postmarketing surveillance safety data. The authors focus on improved blood count control, rates of thromboembolic events, symptom improvement, and markers of disease modification such as reduction of JAK2V617F allele burden in patients treated with ruxolitinib. They also discuss the well-characterized safety profile of ruxolitinib regarding hematologic and other adverse events of interest. In the 10 years since its approval, ruxolitinib remains a safe and effective standard-of-care treatment for PV. As the treatment landscape for PV continues to evolve in the coming years, the efficacy and safety profiles of ruxolitinib suggest it will remain a preferred treatment as monotherapy and as a potential backbone of future combination regimens., (© 2024 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Despite the study of BCR::ABL1-positive and -negative myeloproliferative neoplasms (MPNs) providing seminal insights into cancer biology, tumor evolution and precision oncology over the past half century, significant challenges remain. MPNs are clonal hematopoietic stem cell-derived neoplasms with heterogenous clinical phenotypes and a clonal architecture which impacts the often-complex underlying genetics and microenvironment. The major driving molecular abnormalities have been well characterized, but debate on their role as disease-initiating molecular lesions continues. The introduction of the ABL1 tyrosine kinase inhibitors have been extremely successful in the treatment of chronic myeloid leukemia with most patients having a near-normal life expectancy. Similar success has, however, not been achieved for BCR::ABL1-negative MPNs in terms of disease course modification and most patients remain incurable. In both disease categories, genomic instability seems to increase the risk of disease progression to accelerated/blast phase, which is resistant/refractory to conventional treatment and associated with a poor prognosis. To address some of these issues, the late John Goldman and Tariq Mughal founded a scientific and clinical platform in 2006, the Post-American Society of Hematology (ASH) MPN workshop, to appraise novel cancer biology, candidate therapeutic targets, treatments and other clinical challenges and pay tribute to all the many scientists and clinicians around the world instrumental to the progress made and continuing advances being made. This paper summarizes some of the recent data discussed at the 18 th edition of the workshop and includes reference to some data presented or published after the workshop, including the 26 th John Goldman CML conference., (© 2025 John Wiley & Sons Ltd.)

Introduction: Treatment discontinuation and treatment-free remission (TFR) emerged as the new goal of therapy in patients with chronic myeloid leukemia in chronic phase (CML-CP). Although uncommon, some patients may still experience molecular or hematologic relapse after treatment discontinuation, even after a prolonged duration of remission., Case Presentation: In this case series, we report the outcome of 3 patients with CML-CP who were treated with tyrosine kinase inhibitors and achieved a deep molecular response for ≥8 years, but eventually experienced disease relapse after treatment discontinuation. We discuss the importance of regular monitoring after treatment discontinuation as well as future strategies to increase the chances of TFR in patients with CML-CP., Conclusion: Despite the high chances of TFR after TKI discontinuation in patients with CML-CP who remain in sustained and prolonged DMR, relapses can still occur. Regular monitoring with RT-PCR is recommended to detect any recurrence of the disease., (© 2024 S. Karger AG, Basel.)

Background/Objectives: Red blood cell transfusions for anemia impose high financial and healthcare resource utilization burdens on patients with myelofibrosis (MF). This study estimates projected differences in medical costs and transfusion-related cost and time burdens with momelotinib vs. ruxolitinib or best available therapy (BAT) in Janus kinase (JAK) inhibitor-naive and -experienced patients. Methods: Analyses used 24-week transfusion data from the phase 3 SIMPLIFY-1 and SIMPLIFY-2 trials and cost estimates from a study of adult patients with MF using the US IBM MarketScan Commercial database. The analyses were stratified by transfusion status at baseline (transfusion dependent [TD], transfusion independent/requiring [TI/TR]). Subgroup analyses were conducted among patients with anemia (moderate anemia, hemoglobin ≥ 8 to <10 g/dL; moderate-to-severe anemia, hemoglobin < 10 g/dL) and for patients aged ≥65 years. Cost estimates for patients aged ≥65 years were extracted from a study using the Medicare Fee-for-Service database. Results: In JAK inhibitor-naive patients, momelotinib was projected to result in cost and time savings vs. ruxolitinib in both TD and TI/TR patients across all populations evaluated. Projected cost and time savings were also observed with momelotinib vs. BAT in JAK inhibitor-experienced patients across all populations evaluated, primarily in TD patients. Conclusions: These results suggest that momelotinib may provide medical and transfusion-related cost and time burden offsets for both JAK inhibitor-naive and -experienced patients with MF.

The outcomes of patients with acute myeloid leukemia (AML) and bone marrow fibrosis (MF) are not well defined. The study objectives were to evaluate the degrees of MF in AML, and corresponding response rates and outcomes. We performed a retrospective review of 2302 patients with AML. We annotated the clinical and molecular characteristics, response to therapy, and survival outcomes of patients with bone marrow fibrosis. Overall, 492 patients (21.4%) had a reported microscopic evaluation of MF: 344 (69.9%) had MF grade 0-1 and 148 (30.1%) had MF grade 2-3. Patients with MF 2-3 had a higher proportion of complex cytogenetics (39.2% vs. 24.7%, p = 0.002) JAK2 mutations (25.7% vs. 18%, p = 0.07) and lower proportion of IDH2 (16.9% vs. 25.9%, p = 0.03) and CEBPA (15.5% vs. 27.6%, p = 0.006) mutations. 64% were treated with low-intensity chemotherapy (LIT) and 36.1% with intensive chemotherapy (IT). The complete remission (CR)/CR with incomplete count recovery (CRi) rates were 63.5% with IC versus 37.9% with LIT (p = 0.007). In patients aged 60 or older 4-week mortality was 12.5% with IC vs. 9.3% with LIT (p = 0.8). The median overall survival (OS) was 14.2 with MF 0-1 versus 7.5 months with MF 2-3 (p < 0.005). In patients aged 60 or older with MF 2-3 median OS was 6.5 months with IT versus 7.0 months with LIT (p = 0.19). In a multivariate analysis, grade 2-3 MF (HR 2.0, 95%CI 1.59-2.51) was the strongest prognostic factor for survival. In summary, grade 2-3 MF in AML is associated with worse outcomes., Competing Interests: Declarations Ethical approval This study was approved by the MD Anderson Review Board. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Twenty adults with newly diagnosed (ND) or relapsed/refractory (RR) Ph-positive acute lymphoblastic leukemia (ALL), or chronic myeloid leukemia in lymphoid blast phase (CML-LBP), were treated with mini-hyperCVD, ponatinib, and blinatumomab. Complete molecular response was achieved in 78% of ND patients, while CR/CRi was achieved in 100% of RR and CML-LBP. The 3-year overall survival rate was 76% (95% CI, 47%-90%)., (© 2024 Wiley Periodicals LLC.)

There has been remarkable progress in the development of novel therapeutic approaches for patients with polycythemia vera (PV). Historically, therapy goals in PV were to mitigate thrombotic risks and control blood counts and symptoms. There is now increased focus on disease modification through progressive attrition of JAK2 -mutant stem/progenitor cells. The approval of ropeginterferon, a novel monoPEGylated interferon, coupled with findings from LOW-PV and longer-term data from CONTINUATION-PV that strongly support a disease-modifying effect for interferon therapy, have transformed the treatment paradigm for this disorder. Results from MAJIC-PV demonstrate that disease modification can also be induced with JAK inhibitors, suggesting an urgent need to incorporate prospective molecular monitoring into PV trials. Novel agents, such as hepcidin mimetics, aim to help patients with PV restore normal hematocrit levels and become phlebotomy-free. In this review, we will summarize past, current and future approaches to PV management and highlight findings from key clinical studies.

Abstract: With emerging new drugs in myelofibrosis (MF), a robust and harmonized framework for defining the severity of anemia and response to treatment will enhance clinical investigation and facilitate interstudy comparisons. Accordingly, the lead authors on the 2013 edition of the International Working Group-European LeukemiaNet (IWG-ELN) response criteria in MF were summoned to revise their document with the intent to (1) account for gender-specific differences in determining hemoglobin levels for eligibility criteria; (2) revise the definition of transfusion-dependent anemia (TDA) based on current restrictive transfusion practices; and (3) provide a structurally simple and easy to apply response criteria that are sensitive enough to detect efficacy signals (minor response) and also account for major responses. The initial draft of the 2024 IWG-ELN proposed criteria was subsequently circulated around a wider group of international experts and their feedback incorporated. The proposed articles include new definitions for TDA (≥3 units in the 12 weeks before study enrollment) and hemoglobin thresholds for eligibility criteria (<10 g/dL for women and <11 g/dL for men). The revised document also provides separate (TDA vs non-TDA) and graded (major vs minor response) response criteria while preserving the requirement for a 12-week period of screening and observation on treatment., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

The advent of JAK inhibitors (JAKi) inaugurated a novel era in the treatment of myelofibrosis (MF), a myeloproliferative neoplasm with heterogeneous clinical manifestations. Four JAKi have been approved for intermediate or high-risk MF, in the US. Regulatory approval of the first JAK1/2 inhibitor, ruxolitinib, in 2011 transformed the landscape of MF by markedly controlling splenomegaly and constitutional symptoms, improving patients' lives, and prolonging survival. Fedratinib, the second approved JAKi, is preferred in the second-line setting. Ruxolitinib and fedratinib can cause myelosuppression and are recommended for patients with myeloproliferative MF. Approval of 2 less myelosuppressive JAKi, pacritinib and momelotinib, provided essential treatment options for patients with severe thrombocytopenia and anemia, respectively. Pacritinib and momelotinib are potent ACVR1 inhibitors, resulting in significant anemia benefits. Transfusion independence was achieved with momelotinib in severely anemic patients, and association of transfusion independence with prolonged overall survival was demonstrated. Judicious treatment decisions of JAKi can be made with in-depth understanding of the pivotal clinical trials on JAKi and their therapeutic attributes and should be guided by the dominant clinical manifestations and the type/degree of cytopenia(s). This article reviews our clinical approach to treatment with JAKi and their sequencing in MF patients by presenting 3 clinical vignettes., (Copyright © 2024 American Society of Hematology.)

CXCR4 cell surface expression is critical for the homing of T regulatory (Treg) cells to the bone marrow (BM). We hypothesize that CXCR4 enrichment on Tregs cell surface may abbreviate their transit time to reach BM. Umbilical cord-blood CD25 + Tregs underwent CXCR4 dual enrichment and ex vivo expansion using the CRANE process to generate CXCR4-enriched Tregs (Treg CXCR4 ) cells, which showed a faster migration across the Transwell membrane toward CXCL12/stromal cell-derived factor 1α (SDF1α) at 15, 30, and 60 min, when compared to unmanipulated Treg control cells ( p  < 0.0001). Treg CXCR4 exhibited preferential homing to BM in vivo at 12 and 24 h. Metacluster analysis of BM showed a decrease in CD8 + and an increase in CD39 and CD73 and CXCR5 when compared to Treg control . Treg CXCR4 decreased plasma TGF-β1/β2 and IFN-γ levels. When compared to control, Treg CXCR4 cells decreased in CD8 + T cell, IFN-γ, and TNF-α expression in BM. We conclude that Treg CXCR4 show enhanced migration toward CXCL12/SDF1α and a preferential homing to BM resulting in resolution of inflammation., Competing Interests: S.P. has an equity interest in, holds patents for, receives royalties and research funding from, and is a member of the board of directors/advisory committee for Cellenkos Inc. C.R.F. received research funding from 4D, AbbVie, Acerta, Adaptimmune, Allogene, Amgen, Bayer, Celgene, Cellectis, Cellenkos, EMD, Gilead, Genentech/Roche, Guardant, Iovance, Janssen Pharmaceutical, Kite, MorphoSys, Nektar, Novartis, Pfizer, Pharmacyclics, Sanofi, Takeda, TG Therapeutics, Xencor, Ziopharm, Burroughs Wellcome Fund, Eastern Cooperative Oncology Group, National Cancer Institute, and Cancer Prevention and Research Institute of Texas: CPRIT Scholar in Cancer Research and consulting fees from AbbVie, Bayer, BeiGene, CelgeneDenovo Biopharma, Epizyme, Genentech/Roche, Genmab, Gilead, Karyopharm, Pharmacyclics/Janssen, Seagen, and Spectrum. T.S. is an employee of Cellenkos Inc. L.M. is a consultant/advisor/speaker: Cogent, GlaxoSmithKline, MorphoSys, and PharmaEssentia. The authors declare that this study received funding from Cellenkos Inc., (© 2024 The Author(s).)

Background: The dual inhibition of the BCR::ABL1 tyrosine kinase and BCL-2 could potentially deepen the response rates of chronic myeloid leukemia in chronic phase (CML-CP). This study evaluated the safety and efficacy of the combination of dasatinib and venetoclax., Methods: In this phase 2 trial, patients with CML-CP or accelerated phase (clonal evolution) received dasatinib 50 mg/day for three courses; venetoclax was added in course 4 for 3 years. The initial venetoclax dose was 200 mg/day continuously but reduced later to 200 mg/day for 14 days, and to 100 mg/day for 7 days per course once a molecular response (MR)4.5 was achieved. After 3 years of combination, patients were maintained on single-agent dasatinib. The primary end point was the rate of major molecular response (MMR) by 12 months of combination., Results: Sixty-five patients were treated. Their median age was 46 years (range, 23-73). By 12 months of combination, the MMR, MR4, and MR4.5 rates were 86%, 53%, and 45%, respectively. After a median follow-up of 42 months, the 4-year event-free and overall survival rates were 96% and 100%, respectively. Outcomes with the combination were comparable to historical outcomes with single-agent dasatinib (cumulative 12-months MMR rate of 79% with both strategies). The incidence of grade 3-4 neutropenia was 22% with the combination and 11% with single-agent dasatinib (p < .001)., Conclusions: Treatment with dasatinib and venetoclax was safe and effective in CML-CP. The cumulative response rates with the combination were similar to those with single-agent dasatinib. Further follow-up is needed to evaluate the rates of durable deep molecular response and treatment-free remission., (© 2024 American Cancer Society.)

Myeloproliferative neoplasms (MPN) are characterized by a clonal proliferation of myeloid lineage cells within the bone marrow. The classical BCR-ABL negative MPNs are comprised of polycythaemia vera, essential thrombocythaemia and primary myelofibrosis. Historically, the majority of MPNs are diagnosed in adults older than 60 years of age; however, in recent years, there has been recognition of MPNs in the adolescent and young adult (AYA) population. AYAs with MPN, typically defined as between the ages of 15 and 39 years old, may comprise up to 20% of patients diagnosed with MPN. They demonstrate unique patterns of driver mutations and thrombotic events and remain at risk for progression to more aggressive disease states. Given the likely long length of time they will live with their disease, there is a significant unmet need in identifying well-tolerated and effective treatment options for these patients, particularly with the advent of disease modification. In this review, we provide a comprehensive overview of the clinical features, disease course and management of AYA patients with MPN and, in doing so, highlight key characteristics that distinguish them from their older counterparts., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Background: An inflammatory bone marrow microenvironment contributes to acquired bone marrow failure syndromes. CK0801, an allogeneic T regulatory (Treg) cell therapy product, can potentially interrupt this continuous loop of inflammation and restore hematopoiesis., Methods: In this phase 1 dose-escalation study of CK0801 Treg cells, we enrolled patients with bone marrow failure syndromes with suboptimal response to their prior therapy to determine the safety and efficacy of this treatment for bone marrow failure syndromes., Results: We enrolled nine patients with a median age of 57 years (range, 19 to 74) with an underlying diagnosis of aplastic anemia (n=4), myelofibrosis (n=4), or hypoplastic myelodysplasia (n=1). Patients had a median of three prior therapies for a bone marrow failure syndrome. Starting dose levels of CK0801 were 1 × 10 6 (n=3), 3 × 10 6 (n=3), and 10 × 10 6 (n=3) cells per kg of ideal body weight. No lymphodepletion was administered. CK0801 was administered in the outpatient setting with no infusion reactions, no grade 3 or 4 severe adverse reactions, and no dose-limiting toxicity. At 12 months, CK0801 induced objective responses in three of four patients with myelofibrosis (two had symptom response, one had anemia response, and one had stable disease) and three of four patients with aplastic anemia (three had partial response). Three of four transfusion-dependent patients at baseline achieved transfusion independence. Although the duration of observation was limited at 0.9 to 12 months, there were no observed increases in infections, no transformations to leukemia, and no deaths., Conclusions: In previously treated patients, CK0801 demonstrated no dose-limiting toxicity and showed evidence of efficacy, providing proof of concept for targeting inflammation as a therapy for bone marrow failure. (Funded by Cellenkos Inc.; Clinicaltrials.gov number, NCT03773393.).

Mastocytosis is a heterogeneous group of disorders comprising cutaneous mastocytosis, systemic mastocytosis, and mast cell sarcoma. It is associated with a variety of symptoms related to the release of mast cell mediators and mast cell tissue infiltration. Referral to specialized centers with expertise in the management of mastocytosis and multidisciplinary collaboration with subspecialists (eg, allergists for the management of anaphylaxis and drug hypersensitivities, anesthesiologists for invasive procedures or surgery, high-risk obstetrician for pregnancy) is recommended. The NCCN Guidelines for Systemic Mastocytosis provide evidence- and consensus-based recommendations for the diagnosis and comprehensive care of patients with systemic mastocytosis. The multidisciplinary panel of experts convenes at least once a year to review requested changes to the guidelines from both internal and external entities as well as to discuss data on existing and new therapies. These NCCN Guidelines Insights focus on some of the recent updates to the guidelines.

Background: Hypomethylating agents combined with venetoclax are effective regimens in patients with acute myeloid leukaemia who are ineligible for intensive chemotherapy. Decitabine and cedazuridine (ASTX727) is an oral formulation of decitabine that achieves equivalent area-under-curve exposure to intravenous decitabine. We performed a single centre phase 2 study to evaluate the efficacy and safety of ASTX727 plus venetoclax., Methods: This study enrolled patients with newly diagnosed (frontline treatment group) acute myeloid leukaemia who were ineligible for intensive chemotherapy (aged ≥75 years, an Eastern Cooperative Oncology Group [ECOG] performance status of 2-3, or major comorbidities) or relapsed or refractory acute myeloid leukaemia. Being aged 18 years or older and having an ECOG performance status of 2 or less were requirements for the relapsed or refractory disease treatment cohort, without any limits in the number of previous lines of therapy. Treatment consisted of ASTX727 (cedazuridine 100 mg and decitabine 35 mg) orally for 5 days and venetoclax 400 mg orally for 21-28 days in 28-day cycles. The primary outcome was overall response rate of ASTX727 plus venetoclax. Living patients who have not completed cycle one were not evaluable for response. Safety was analysed in all patients who started treatment. This study was registered on ClinicalTrials.gov (NCT04746235) and is ongoing. The data cutoff date for this analysis was Sept 22, 2023., Findings: Between March 16, 2021, and Sept 18, 2023, 62 patients were enrolled (49 frontline and 13 relapsed or refractory) with a median age of 78 years (IQR 73-82). 36 (58%) were male; 53 (85%) were White, 4 (6%) Black, 2 (3%) Asian and 3 (5%) other or did not answer. 48 (77%) of 62 patients were European LeukemiaNet 2022 adverse risk, 24 (39%) had antecedent myelodysplastic syndromes, 12 (19%) had previously failed a hypomethylating agent, ten (16%) had therapy-related acute myeloid leukaemia, and 11 (18%) had TP53 mutations. The median follow-up time was 18·3 months (IQR 8·8-23·3). The overall response rate was 30 (64%) of 47 patients (95% CI 49-77) in frontline cohort and six (46%) of 13 patients (19-75) in relapsed or refractory cohort. The most common grade 3 or worse treatment-emergent adverse events were febrile neutropenia in 11 (18%) of 62 patients, pneumonia in eight (13%), respiratory failure in five (8%), bacteraemia in four (6%), and sepsis in four (6%). Three deaths occurred in patients in remission (one sepsis, one gastrointestinal haemorrhage, and one respiratory failure) and were potentially treatment related., Interpretation: ASTX727 plus venetoclax is an active fully oral regimen and safe in most older or unfit patients with acute myeloid leukaemia. Our findings should be confirmed in larger multicentric studies., Funding: MD Anderson Cancer Center Support Grant, Myelodysplastic Syndrome/Acute Myeloid Leukaemia Moon Shot, Leukemia SPORE, Taiho Oncology, and Astex Pharmaceuticals., Competing Interests: Declaration of interests GG-M declares grants from Astex, Novartis, AbbVie, Genentech, Aprea, Curis, and Gilead; consulting fees from Astex, Acceleron, and BMS; and payment or honoraria from Astex, Acceleron, AbbVie, Gilead, Curis, Genentech, and BMS. NS declares research funding from Takeda Oncology, Astellas Pharma, Xencor, Stemline Therapeutics, and NextCure; consulting fees from Pfizer, GlaxoSmithKline, NKARTA, Autolus, and Sanofi; and payment or honoraria from Adaptive Biotechnologies, Novartis, Amgen, Takeda Oncology, Pfizer, Astellas Pharma, Sanofi, and BeiGene. GI declares grants from Celgene, Kura Oncology, Syndax, Merck, Cullinan, and Novartis and consulting fees from Novartis, Kura Oncology, and Nuprobe. NJ declares research funding from Pharmacyclics, AbbVie, Genentech, AstraZeneca, BMS, Pfizer, ADC Therapeutics, Cellectis, Adaptive Biotechnologies, Precision Biosciences, Fate Therapeutics, Kite and Gilead, Mingsight, Takeda, Medisix, Loxo Oncology, Novalgen, Dialectic Therapeutics, Newave, TransThera Sciences, Novartis, Carna Biosciences, Sana Biotechnology, and Kisoji Biotechnology and honoraria or advisory board participation from Pharmacyclics, Janssen, AbbVie, Genentech, AstraZeneca, BMS, Adaptive Biotechnologies, Kite and Gilead, Precision Biosciences, Beigene, Cellectis, MEI Pharma, Ipsen, CareDX, MingSight, and Novalgen. AM declares research funding from Lin Biosciences and Chimeric Therapeutics and travel support from Cero Bio. EJ declares grants from AbbVie, Adaptive Biotechnologies, Amgen, Pfizer, and Takeda and consulting fees from AbbVie, Adaptive Biotechnologies, Amgen, BMS, Genentech, Incyte, Novartis, Pfizer, and Takeda. CDD declares grants from AbbVie, Astex, ImmuneOnc, BMS, Cleave, Foghorn, Loxo, Rigel, and Servier; consulting fees from Amgen, AbbVie, Astellas, BMS, Genmab, GSK, Gilead, Jazz, Shrodinger, Servier, and Stemline; payment or honoraria from AbbVie, Astellas, BMS, Jazz, and Servier; travel support from Servier; and participation on a data safety board for Genmab. TK declares grants from BMS, AbbVie, Amgen, Ascentage Pharma Group, Astellas Pharma, DrenBio, Astex, AstraZeneca, BMS, Celgene, Incyte, Cellenkos, Cyclacel, Delta-Fly Pharma, Genentech, Genfleet, Glycomimetics, Iterion, Janssen, Jazz Pharmaceuticals, Pfizer, Pulmotect, Regeneron, and SELLAS; consulting fees from AbbVie, Agios, Daiichi Sankyo, Genentech, Genzyme, Jazz Pharmaceuticals, Liberum, Novartis, Pfizer, PinotBio, Pulmotect, Sanofi-Aventis, and Servier; and payment or honoraria from AbbVie, Agios, Daiichi Sankyo, DAVA Oncology, Delta-Fly, DrenBio, Genentech, Genfleet, Genzyme, Jazz Pharmaceuticals, Liberum, Novartis, Pfizer, Rigel, Sanofi-Aventis, SELLAS, and Servier. ND declares grants from Daiichi-Sankyo, BMS, Pfizer, Gilead, Servier, Genentech, Astellas, AbbVie, ImmunoGen, Amgen, Trillium, Hanmi, Trovagene, FATE Therapeutics, Novimmune, Glycomimetics, and KITE and consulting fees from Daiichi-Sankyo, BMS, Pfizer, Gilead, Servier, Genentech, Astellas, AbbVie, ImmunoGen, Amgen, Trillium, Arog, Novartis, Jazz, Celgene, Syndax, Shattuck Labs, Agios, KITE, and Stemline and Menarini. MK declares grants from AbbVie, Genentech, Gilead, ImmunoGen, MEI Pharma, Precision Biosciences, Rafael Pharmaceutical, Sanofi-Aventis, and Stemline Therapeutics; consulting fees from AbbVie, AstraZeneca, Boehringer, Hoffman-La Roche, Genentech, Gilead, Janssen, Legend Biotech, MEI Pharma, Redona, Sanofi-Aventis, Sellas, Stemline Therapeutics, and Vincerx; participation on an advisory board for AbbVie, Auxenion, GmbH, Bakx Therapeutics, Dark Blue Therapeutics, Hoffman-La Roche, Genentech, Gilead, Stemline Therapeutics, and Vincerx; has a board of directors role for Immune Oncology; clinical trial support from AbbVie, AstraZeneca, Cellectis, Genentech, Janssen, Pfizer, Sanofi-Aventis, and Stemline Therapeutics; and intellectual property from Reata Pharmaceuticals. HK declares grants from AbbVie, Amgen, Ascentage, BMS, Daiichi-Sankyo, Immunogen, Jazz, and Novartis and payment or honoraria from AbbVie, Amgen, Amphista, Ascentage, Astellas, Biologix, Curis, Ipsen Biopharmaceuticals, KAHR Medical, Labcorp, Novartis, Pfizer, Shenzhen Target Rx, Stemline, and Takeda. FR declares clinical trial support from Astex and Taiho Oncology and payment or honoraria from Taiho Oncology. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In the recent years, landmark advancements in the treatment of polycythemia vera (PV) have been achieved. We witnessed the regulatory approval of ropeginterferon and the advanced clinical development of other novel agents that may affect the underlying pathophysiological mechanisms of the disease. Agents with the potential of disease modification may soon overtake preceding treatment options that were based on the patient's age and history of thrombosis. Recent studies using ropeginterferon in low-risk PV patients earlier in the disease course challenge the current treatment paradigm and shift the focus on modifying the course of the disease. Hepcidin mimetics offer an excellent alternative to phlebotomy, providing better quality of life, and may lead to improved outcomes in PV by tight hematocrit control. Novel agents, such as histone deacetylase inhibitors, hold promise to complement the therapeutic landscape of PV and might be particularly promising in rationale combinations. Ruxolitinib is well established as an approved second-line treatment for PV. In the frontline setting, the precise role of ruxolitinib, which also represents an appealing agent in combination regimens, will be determined in ongoing research studies. Longer follow-up is necessary to assess whether novel agents/regimens elicit fewer thromboembolic/ hemorrhagic events and halt disease progression to myelofibrosis and acute myeloid leukemia. We aspire that disease-modifying approaches in PV are on the horizon, and that we will be empowered to ultimately change the natural course of the disease and profoundly impact the lives of PV patients in the near future., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Hypomethylating agents are approved in higher-riskmyelodysplastic syndromes. The combination of a hypomethylating agent with venetoclax is standard of care in acute myeloid leukaemia. We investigated the safety and activity of the first totally oral combination of decitabine plus cedazuridine and venetoclax in patients with higher-risk-myelodysplastic syndromes and chronic myelomonocytic leukaemia., Methods: We did a single-centre, dose-escalation and dose-expansion, phase 1/2, clinical trial. Patients with treatment-naive higher-risk-myelodysplastic syndromes or chronic myelomonocytic leukaemia (risk level categorised as intermediate-2 or higher by the International Prognostic Scoring System) with excess blasts (>5%). Treatment consisted of oral decitabine 35 mg plus cedazuridine 100 mg on days 1-5 and venetoclax (variable doses of 100-400 mg, day 1 to 14, 28-day cycle). The primary outcomes were safety for the phase 1 part and the overall response for the phase 2 part of the study. The trial is ongoing and this analysis was not prespecified. This study is registered with ClinicalTrials.gov, NCT04655755, and is currently enrolling participants., Findings: Between Jan 21, 2021, and Jan 20, 2023, we enrolled 39 patients (nine in phase 1 and 30 in phase 2). The median age was 71 years (range 27-94), 28 (72%) patients were male, and 11 (28%) were female. The maximum tolerated dose was not reached, and the recommended phase 2 dose was established as oral decitabine 35 mg plus cedazuridine 100 mg for 5 days and venetoclax (400 mg) for 14 days. The most common grade 3-4 adverse events were thrombocytopenia (33 [85%] of 39), neutropenia (29 [74%]), and febrile neutropenia (eight [21%]). Four non-treatment-related deaths occurred on the study drugs due to sepsis (n=2), lung infection (n=1), and undetermined cause (n=1). The median follow-up time was 10·8 months (IQR 5·6-16·4). The overall response rate was 95% (95% CI 83-99; 37/39). 19 (49%) patients proceeded to hematopoietic stem-cell transplantation., Interpretation: This early analysis suggests that the combination of oral decitabine plus cedazuridine with venetoclax for higher-risk-myelodysplastic syndromes and chronic myelomonocytic leukaemia is safe in most patients, with encouraging activity. Longer follow-up will be needed to confirm these data., Funding: MD Anderson Cancer Center, MDS/AML Moon Shot, Genentech/AbbVie, and Astex Pharmaceuticals., Competing Interests: Declaration of interests GM-B declares research support from Takeda, Rigel, and IFN Therapeutics. KSC declares research funding from Amgen and consultancy fees from AbbVie. JI declares funding from the US National Institutes of Health, the Leukemia Research Foundation, and the US Department of Defense, and honoraria from AstraZeneca. KS declares consultancy fees from Novartis and honoraria from Otsuka Pharmaceuticals and Amgen. NS declares grants from Takeda Oncology, Astellas Pharma, Xencor, Stemline Therapeutics, and Nexcure; consultancy fees from Pfizer, GSK, NKARTA, and Sanofi; and honoraria from Adaptive Biotechologies, Novartis, Amgen, Takeda, Pfizer, Astellas Pharma, Sanofi, and BeiGene. GCI declares consultancy fees from Novartis, Kura Oncology, and Nuprobe; and research funding from Celgene, Kura Oncology, Syndax, Merck, Cullinan, and Novartis. ND declares grants from Daiichi-Sankyo, Bristol Myers Squibb (BMS), Pfizer, Gilead, Servier, Genentech, Astellas, AbbVie, ImmunoGen, Amgen, Trillium, Hanmi, Trovagene, FATE Therapeutics, Novimmune, Glycomimetics, and KITE; and consultancy fees from Daiichi-Sankyo, BMS, Pfizer, Gilead, Servier, Genentech, Astellas, AbbVie, ImmunoGen, Amgen, Trillium, Arog, Novartis, Jazz Pharmaceuticals, Celgene, Syndax, Shattuck Labs, Agios, KITE, and Stemline/Menarini. TMK declares grants from BMS, Abbvie, Amgen, Ascentage Pharma Group, Astellas Pharma, DrenBio, Astex, AstraZeneca, Celgene, Incyte, Cellenkos, Cyclacel, Delta-Fly Pharma, Genentech, Genfleet, Glycomimetics, Iterion, Janssen, Jazz Pharmaceuticals, Pfizer, Pulmotect, Regeneron, and SELLAS; consultancy fees from AbbVie, Agios, Daiichi Sankyo, Genentech, Genzyme, Jazz Pharmaceuticals, Liberum, Novartis, Pfizer, PinotBio, Pukmotect, Sanofi-Aventis, Servier; and honoraria from AbbVie, Agios, Daiichi Sankyo, DAVA Oncology, Delta-Fly, DrenBio, Genentech, Genfleet, Genzyme, Jazz Pharmaceuticals, Liberum, Novartis, Pfizer, Rigel, Sanofi-Aventis, SELLAS, and Servier. FR declares research funding from ASTEX and TAIHO. EJ received research grants from AbbVie, Adaptive Biotechnologies, Amgen, Pfizer, and Takeda; and consultancy fees from AbbVie, Adaptive Biotechnologies, Amgen, BMS, Genentech, Incyte, Novartis, Pfizer, and Takeda. HMK declares research funding from Abbvie, Amgen, Ascentage, BMS, Daiichi Sankyo, Immunogen, Jazz Pharmaceuticals, and Novartis; and honoraria from Abbvie, Amgen, Amphista, Ascentage, Astellas, Biologix, Curis, Ipsen Biopharmaceuticals, KAHR Medical, Labcorp, Novartis, Pfizer, Precision Biosciences, Shenzhen Target Rx, Stemline, and Takeda. GG-M declares research funding from Astex Pharmaceuticals, Novartis, Abbvie, BMS, Genentech, Aprea Therapeutics, Curis, and Gilead Sciences; consultancy fees from Astex Pharmaceuticals, Acceleron Pharma, and BMS; and honoraria from Astex Pharmaceuticals, Acceleron Pharma, Abbvie, Novartis, Gilead Sciences, Curis, Genentech, and BMS. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Interferons are cytokines with immunomodulatory properties and disease-modifying effects that have been used to treat myeloproliferative neoplasms (MPNs) for more than 35 years. The initial use of interferons was limited due to difficulties with administration and a significant toxicity profile. Many of these shortcomings were addressed by covalently binding polyethylene glycol to the interferon structure, which increases the stability, prolongs activity, and reduces immunogenicity of the molecule. In the current therapeutic landscape, pegylated interferons are recommended for use in the treatment of polycythemia vera, essential thrombocythemia, and primary myelofibrosis. We review recent efficacy, molecular response, and safety data for the two available pegylated interferons, peginterferon alfa-2a (Pegasys) and ropeginterferon alfa-2b-njft (BESREMi). The practical management of interferon-based therapies is discussed, along with our opinions on whether to and how to switch from hydroxyurea to one of these therapies. Key topics and questions related to use of interferons, such as their safety and tolerability, the significance of variant allele frequency, advantages of early treatment, and what the future of interferon therapy may look like, will be examined. Pegylated interferons represent an important therapeutic option for patients with MPNs; however, more research is still required to further refine interferon therapy., Competing Interests: PV: Consulting fees (AbbVie, Amgen, Blueprint Medicines, Cogent Biosciences, Incyte, CTI BioPharma Corp, Daiichi Sankyo, GlaxoSmith Kline, Karyopharm, Novartis, Pfizer, Genentech, Servier, Stemline, MorphoSys, LAVA Therapeutics); honoraria for lectures/advisory boards (Incyte, Blueprint Medicines, CTI Biopharma). JM: Grants (PharmaEssentia, Novartis, Roche, Geron, Abbie, Kartos, Karyopharm); consulting fees (PharmaEssentia, CTI, Incyte, Roche, Novartis, Merck, Geron, AbbVie, BMS, Kartos, MorphoSys, Galecto, Imago); honoraria for lectures/advisory boards (BMS); monitoring or advisory board (Incyte, Galecto); meeting/travel support (Kartos). PB: Grants (Incyte, CTI, MorphoSys, Kartos, Telios, Ionis, Disc, Blueprint, Cogent, Geron, Janssen, Sumitomo, BMS, Karyopharm); consulting fees (Incyte, BMS, CTI, GSK, AbbVie, MorphoSys, Karyopharm, PharmaEssentia, Blueprint, Cogent, Novartis, Jubilant, Morphic, Ono, Sumitomo); honoraria for lectures/advisory boards (Incyte, Blueprint, GSK, CTI, AbbVie, Sumitomo, PharmaEssentia). GH: Grants (Incyte); consulting fees (PharmaEssentia, Protagonist, AbbVie, GSK, Pfizer, Novartis, MorphoSys, Cogent, Pharmaxis); monitoring or advisory board (PharmaEssentia, Protagonist, AbbVie, GSK, Pfizer, Novartis, MorphoSys); stock/stock options (Regeneron Pharmaceuticals). AY: Consulting fees (Incyte, CTI Pharma, PharmaEssentia, Pfizer, Novartis, Acceleron Pharma, Servier, AbbVie, Apellis, Gilead, Notable Labs); meeting/travel support (Incyte). JMP: Consulting fees (Sierra Oncology, MorphoSys, CTI, Protagonist). ATG: Consulting fees (PharmaEssentia, MorphoSys, CTI, Biopharma, Bristol-Meyers Squibb, Sierra Oncology/GSK, Kartos, AbbVie, Imago Biosciences). LM: Advisory board (MorphoSys). ATK: Grants (BMS, Protagonist, Janssen, GSK, MorphoSys); consulting fees (GSK, AbbVie, Incyte); honoraria for lectures/advisory boards (PharmaEssentia, Novartis, BMS); monitoring or advisory board (Incyte). RKR: Grants (Incyte, Ryvu, MorphoSys, Zentalis); consulting fees (MorphoSys, CTI, GSK, Stemline, Blueprint, SDP, Servier, Zentalis, BMS, Galectco, AbbVie, PharmaEssentia, Cogent, Kartos); honoraria for lectures/advisory boards (Protagonist, Karyopharm, GSK); monitoring or advisory board (Kartos). RM: Consulting fees (Incyte, PharmaEssentia, CTI, AbbVie, GSK, BMS, Genentech). SV: The author declares that there is no conflict of interest., (© The Author(s), 2024.)

Abstract: The detection of measurable residual disease (MRD) is the strongest predictor of relapse in acute lymphoblastic leukemia (ALL). Using inotuzumab ozogamicin in the setting of MRD may improve outcomes. Patients with ALL in first complete remission (CR1) or beyond (CR2+) with MRD ≥ 1 × 10-4 were enrolled in this phase 2 trial. Inotuzumab was administered at 0.6 mg/m2 on day 1 and 0.3 mg/m2 on day 8 of cycle 1, then at 0.3 mg/m2 on days 1 and 8 of cycles 2-6. Twenty-six consecutive patients with a median age of 46 years (range, 19-70 years) were treated. Nineteen (73%) were in CR1 and seven (27%) in CR2+; 16 (62%) had Philadelphia chromosome-positive ALL. Fifteen (58%) had baseline MRD ≥ 1 × 10-3. A median of 3 cycles (range, 1-6) were administered. Eighteen (69%) patients responded and achieved MRD negativity. After a median follow-up of 24 months (range, 9-43), the 2-year relapse-free survival rate was 54% and the 2-year overall survival rate was 60% in the entire cohort. Most adverse events were low grade; sinusoidal obstruction syndrome was noted in 2 patients (8%). In summary, inotuzumab ozogamicin resulted in favorable survival, MRD negativity rates, and safety profiles for patients with ALL and MRD-positive status. This study was registered at www.ClinicalTrials.gov as #NCT03441061., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Aim: To estimate projected US-based cost and time burden for patients with myelofibrosis and anemia treated with momelotinib compared with danazol. Methods: Cost and time burden were calculated based on the transfusion status of patients in the MOMENTUM trial and estimates extracted from previous studies. Results: Reductions in transfusion associated with momelotinib are projected to result in cost and time savings compared with danazol in transfusion-dependent and transfusion-independent/requiring patients with myelofibrosis, respectively: annual medical costs ($53,143 and $46,455 per person), outpatient transfusion costs ($42,021 and $8,370 per person) and annual time savings (173 and 35 h per person). Conclusion: Fewer transfusions with momelotinib are projected to result in cost and time savings in patients with myelofibrosis and anemia compared with danazol.