Toward a more patient-centered drug development process in clinical trials for patients with myelodysplastic syndromes/neoplasms (MDS): Practical considerations from the International Consortium for MDS (icMDS).

Notable treatment advances have been made in recent years for patients with myelodysplastic syndromes/neoplasms (MDS), and several new drugs are under development. For example, the emerging availability of oral MDS therapies holds the promise of improving patients' health-related quality of life (HRQoL). Within this rapidly evolving landscape, the inclusion of HRQoL and other patient-reported outcomes (PROs) is critical to inform the benefit/risk assessment of new therapies or to assess whether patients live longer and better, for what will likely remain a largely incurable disease. We provide practical considerations to support investigators in generating high-quality PRO data in future MDS trials. We first describe several challenges that are to be thoughtfully considered when designing an MDS-focused clinical trial with a PRO endpoint. We then discuss aspects related to the design of the study, including PRO assessment strategies. We also discuss statistical approaches illustrating the potential value of time-to-event analyses and their implications within the estimand framework. Finally, based on a literature review of MDS randomized controlled trials with a PRO endpoint, we note the PRO items that deserve special attention when reporting future MDS trial results. We hope these practical considerations will facilitate the generation of rigorous PRO data that can robustly inform MDS patient care and support treatment decision-making for this patient population.

Race/ethnic associations with comprehensive cancer center access and clinical trial enrollment for acute leukemia.

BACKGROUND: Clinical trial participation at Comprehensive Cancer Centers (CCC) is inequitable for minoritized race/ethnic groups with acute leukemia. CCCs care for a high proportion of adults with acute leukemia. It is unclear if participation inequities are due to CCC access, post-access enrollment, or both. METHODS: We conducted a retrospective cohort study of adults with acute leukemia (2010-2019) residing within Massachusetts, the designated catchment area of the Dana-Farber/Harvard Cancer Center (DF/HCC). Individuals were categorized as non-Hispanic Asian (NHA), Black (NHB), White (NHW), Hispanic White (HW), or Other. Decomposition analyses assessed covariate contributions to disparities in (1) access to DF/HCC care and (2) post-access enrollment. RESULTS: Of 3698 individuals with acute leukemia, 85.9% were NHW, 4.5% HW, 4.3% NHB, 3.7% NHA, and 1.3% Other. Access was lower for HW (age- and sex-adjusted OR 0.64 95%CI 0.45,0.90) and reduced post-access enrollment for HW (aOR 0.54 95%CI 0.34,0.86) and NHB (aOR 0.60 95%CI 0.39,0.92) compared to NHW. Payor and socioeconomic status (SES) accounted for 25.2% and 21.2% of the +1.1% absolute difference in HW access. Marital status and SES accounted for 8.0% and 7.0% of the -8.8% absolute disparity in HW enrollment; 76.4% of the disparity was unexplained. SES and marital status accounted for 8.2% and 7.1% of the -9.1% absolute disparity in NHB enrollment; 73.0% of the disparity was unexplained. CONCLUSIONS: A substantial proportion of race/ethnic inequities in acute leukemia trial enrollment at CCCs are from post-access enrollment, the majority of which was not explained by sociodemographic factors.

Treatment completion, asparaginase completion, and oncologic outcomes among children, adolescents and young adults with acute lymphoblastic leukemia treated with DFCI Consortium Protocols.

Adolescents and young adult (AYA) patients with acute lymphoblastic leukemia (ALL) face worse outcomes than children. While pediatric-inspired protocols have improved outcomes, the ability of patients to complete these intensive regimens and the reasons for discontinuation are unknown. We analyzed a cohort of 332 AYA patients (aged 15-49 years) and 1159 children (aged 1-14 years) with Ph-negative ALL treated on DFCI consortium protocols. We found that AYA patients completed treatment at lower rates than children (60.8% vs. 89.7%, p < 0.001), primarily due to higher rates of early treatment failure (14.5% vs. 2.4%, p < 0.001). Withdrawal from treatment for toxicity, social/personal, or unknown reasons was uncommon, but higher among AYA patients (9.3% vs 4.7%, p = 0.001). Patients who remained on assigned therapy for one year had favorable overall survival (AYA 5-year OS 88.9%; children 5-year OS 96.4%; p < 0.001). Among patients who continued treatment for 1 year, AYA patients completed asparaginase (defined as receiving 26+ weeks) at lower rates than children (79.1% vs. 89.6%, p < 0.001). Patients who received more weeks of consolidation asparaginase had higher overall and event-free survival. Efforts should focus on identifying patients at risk for early treatment failure and optimizing asparaginase delivery.

In-Hospital and readmission outcomes of patients with myeloproliferative neoplasms and atrial fibrillation: insights from the National Readmissions Database.

INTRODUCTION: Patients with myeloproliferative neoplasms (MPNs) and atrial fibrillation (AF) are at increased risk of thrombosis and bleeding. However, the risk of thrombosis and bleeding in patients with AF and MPN compared with the general population with AF is unclear. Additionally, traditional risk scores (CHA2DS2-VASC and HAS-BLED) for risk/benefit estimation of thromboprophylaxis in AF do not account for MPN status. Therefore, we aimed to investigate bleeding and thrombosis risk in patients with MPN hospitalized for AF. METHODS: We utilized the National Readmission Database (NRD) to identify patients with AF with and without MPN. Primary bleeding and thrombosis outcomes were in-hospital or 30-day readmission for bleeding or thrombosis, respectively. We propensity score (PS) matched patients with and without MPN. Risk of primary outcomes in MPN was assessed in PS matched cohort using logistic regression. Receiver operating characteristic (ROC) curve used to evaluate predictive ability of CHA2DS2-VASC and HAS-BLED of primary thrombosis and bleeding outcomes, respectively. RESULTS: 24,185 patients without MPN were matched with 1,617 patients with MPN and variables were balanced between groups. Patients with MPN were at increased risk of meeting the thrombosis (OR 1.98, 95% CI 1.23-3.21) but not bleeding (OR 0.87, 95% CI 0.63-1.19) primary outcomes. In MPN, CHA2DS2-VASC predicted thrombosis (C-statistic 0.66, 95% CI 0.54-0.78) but HAS-BLED was a poor predictor of bleeding (C-statistic 0.55, 95% CI 0.46-0.64). CONCLUSION: In patients with AF, MPN was associated with increased risk of bleeding and thrombosis. HAS-BLED scores did not accurately predict bleeding in MPN. Further investigation is needed to refine risk scores in MPN.

Phase Ib study of sabatolimab (MBG453), a novel immunotherapy targeting TIM-3 antibody, in combination with decitabine or azacitidine in high- or very high-risk myelodysplastic syndromes.

The safety and efficacy of sabatolimab, a novel immunotherapy targeting T-cell immunoglobulin domain and mucin domain-3 (TIM-3), was assessed in combination with hypomethylating agents (HMAs) in patients with HMA-naive revised International Prognostic System Score (IPSS-R) high- or very high-risk myelodysplastic syndromes (HR/vHR-MDS) or chronic myelomonocytic leukemia (CMML). Sabatolimab + HMA had a safety profile similar to that reported for HMA alone and demonstrated durable clinical responses in patients with HR/vHR-MDS. These results support the ongoing evaluation of sabatolimab-based combination therapy in MDS, CMML, and acute myeloid leukemia.

Are We Ready For "Triplet" Therapy in Higher-Risk MDS?

Higher-risk Myelodysplastic Syndromes/Neoplasms (MDS) represent an ongoing therapeutic challenge, with few effective therapies, many of which may have limited use in this older patient population often with considerations around comorbidities. Outside of transplant, azacitidine and decitabine remain the only disease-modifying therapies, and are palliative in nature. Recent interest has grown in extending combination chemotherapies used to treat acute myeloid leukemia (AML) to patients with MDS, including novel combination chemotherapy "doublets" and "triplets." In this review, we discuss considerations around combination chemotherapy in MDS, specifically as relates to study design, appropriate endpoints, supportive considerations, and how to integrate these into the current treatment paradigm. New therapies in MDS are desperately needed but also require considerations particular to this unique patient population.

Phase 1 study of JNJ-64619178, a protein arginine methyltransferase 5 inhibitor, in patients with lower-risk myelodysplastic syndromes.

Splicing factor (SF) gene mutations are frequent in myelodysplastic syndromes (MDS), and agents that modulate RNA splicing are hypothesized to provide clinical benefit. JNJ-64619178, a protein arginine methyltransferase 5 (PRMT5) inhibitor, was evaluated in patients with lower-risk (LR) MDS in a multi-part, Phase 1, multicenter study. The objectives were to determine a tolerable dose and to characterize safety, pharmacokinetics, pharmacodynamics, and preliminary clinical activity. JNJ-64619178 was administered on a 14 days on/7 days off schedule or every day on a 21-day cycle to patients with International Prognostic Scoring System (IPSS) Low or Intermediate-1 risk MDS who were red blood cell transfusion-dependent. Twenty-four patients were enrolled; 15 (62.5 %) patients had low IPSS risk score, while 18 (75.0 %) had an SF3B1 mutation. Median duration of treatment was 3.45 months (range: 0.03-6.93). No dose limiting toxicities were observed. The 0.5 mg once daily dose was considered better tolerated and chosen for dose expansion. Twenty-three (95.8 %) patients experienced treatment-emergent adverse events (TEAE). The most common TEAEs were neutropenia (15 [62.5 %]) and thrombocytopenia (14 [58.3 %]). JNJ-64619178 pharmacokinetics was dose-dependent. Target engagement as measured by plasma symmetric di-methylarginine was observed across all dose levels; however, variant allele frequency of clonal mutations in bone marrow or blood did not show sustained reductions from baseline. No patient achieved objective response or hematologic improvement per International Working Group 2006 criteria, or transfusion independence. A tolerable dose of JNJ-64619178 was identified in patients with LR MDS. However, no evidence of clinical benefit was observed.

Temporal trend in survival for chronic myelomonocytic leukemia in the US: a population-based study.

Outcomes for chronic myelomonocytic leukemia (CMML) are insufficiently characterized at the population level. We analyzed epidemiological trends for patients between 2001 and 2017, focusing on age, sex, race, and long-term survivors. Using the Surveillance, Epidemiology, and End Results Program, we studied 3929 patients, in four time-period (tp) cohorts, based on year of diagnosis [2001-2004 (tp1); 2005-2009 (tp2); 2010-2013 (tp3); 2014-2017 (tp4)]. Stable incidence overall, male predominance, and higher incidence for White versus Black and 'Other' races were noted. Three-year relative survival (RS) increased from 27.9% to 36.9% between tp1 and tp4. The most pronounced increase occurred between tp1 and tp2. All subgroups generally experienced RS improvements over time, except notably Black patients. Improvements for patients aged 85+ (3-year RS 8.4-23.6% between tp1 and tp4) and increases in long-term survivors (5-year OS from 13.2-22.3%) were observed. Additional study is warranted to explore these associations, particularly for Black patients.

Classification, risk stratification and response assessment in myelodysplastic syndromes/neoplasms (MDS): A state-of-the-art report on behalf of the International Consortium for MDS (icMDS).

The guidelines for classification, prognostication, and response assessment of myelodysplastic syndromes/neoplasms (MDS) have all recently been updated. In this report on behalf of the International Consortium for MDS (icMDS) we summarize these developments. We first critically examine the updated World Health Organization (WHO) classification and the International Consensus Classification (ICC) of MDS. We then compare traditional and molecularly based risk MDS risk assessment tools. Lastly, we discuss limitations of criteria in measuring therapeutic benefit and highlight how the International Working Group (IWG) 2018 and 2023 response criteria addressed these deficiencies and are endorsed by the icMDS. We also address the importance of patient centered care by discussing the value of quality-of-life assessment. We hope that the reader of this review will have a better understanding of how to classify MDS, predict clinical outcomes and evaluate therapeutic outcomes.

Economic burden during remission and after relapse among older patients with newly diagnosed acute myeloid leukemia without hematopoietic stem cell transplant: A retrospective study using the SEER-Medicare database.

Acute myeloid leukemia (AML) is associated with a substantial clinical and economic burden. This study characterized the magnitude of this burden following initial treatment with standard or less intensive therapies (hypomethylating agents [HMAs]) and throughout different treatment phases post-remission. The Surveillance, Epidemiology, and End Results (SEER) cancer registry (2007-2016) linked with Medicare beneficiary claims (2007-2015) was analyzed. Patients were ≥ 65 years old with AML who initiated chemotherapy or HMAs and achieved remission. Outcomes included baseline characteristics, treatment patterns, clinical outcomes, healthcare resource utilization (HRU), and costs (2019 United States dollar). Economic impacts were stratified by treatment phase (initial treatment, early post-remission, late post-remission, and post-relapse). Early and late post-remission were defined as treatment initiated ≤ 60 days and > 60 days following initial treatment, respectively. A subgroup analysis of patients receiving only HMAs as initial treatment was also conducted. Overall, 530 patients were included (mean age: 74.1 years; 53.6 % male). In the overall analysis, 68.1 % of patients received post-remission treatment; 31.9% had no post-remission treatment. Mean monthly per patient healthcare costs by treatment phase were $45,747 (initial treatment), $30,248 (early post-remission), $23,173 (late post-remission), and $37,736 (post-relapse), driven predominantly by inpatient visits. The HMA subgroup analysis comprised 71 patients (mean age: 78.8 years; 50.7 % male); mean monthly per patient healthcare costs were highest post-relapse. The economic burden of AML among older patients is substantial across all treatment phases. AML treatments that induce and prolong remission may reduce HRU and the economic burden of disease.

Prognostic impact of secondary versus de novo ontogeny in acute myeloid leukemia is accounted for by the European LeukemiaNet 2022 risk classification.

Secondary AML (sAML), defined by either history of antecedent hematologic disease (AHD) or prior genotoxic therapy (tAML), is classically regarded as having worse prognosis than de novo disease (dnAML). Clinicians may infer a new AML diagnosis is secondary based on a history of antecedent blood count (ABC) abnormalities in the absence of known prior AHD, but whether abnormal ABCs are associated with worse outcomes is unclear. Secondary-type mutations have recently been incorporated into the European LeukemiaNet (ELN) 2022 guidelines as adverse-risk features, raising the question of whether clinical descriptors of ontogeny (i.e., de novo or secondary) are prognostically significant when accounting for genetic risk by ELN 2022. In a large multicenter cohort of patients (n = 734), we found that abnormal ABCs are not independently prognostic after adjusting for genetic characteristics in dnAML patients. Furthermore, history of AHD and tAML do not confer increased risk of death compared to dnAML on multivariate analysis, suggesting the prognostic impact of ontogeny is accounted for by disease genetics as stratified by ELN 2022 risk and TP53 mutation status. These findings emphasize the importance that disease genetics should play in risk stratification and clinical trial eligibility in AML.

Effect of BMI on toxicities and survival among adolescents and young adults treated on DFCI Consortium ALL trials.

Adolescent and young adults (AYAs) with acute lymphoblastic leukemia (ALL) treated with asparaginase-containing pediatric regimens are commonly overweight or obese. We studied the association of body mass index (BMI) on outcomes of 388 AYAs aged 15 to 50 years treated on Dana-Farber Cancer Institute (DFCI) consortium regimens (2008-2021). BMI was normal in 207 (53.3%) and overweight/obese in 181 (46.7%). Patients who were overweight or obese experienced higher nonrelapse mortality (NRM; 4-year, 11.7% vs 2.8%, P = .006), worse event-free survival (4-year, 63% vs 77%, P = .003), and worse overall survival (OS; 4-year, 64% vs 83%, P = .0001). Because younger (aged 15-29 years) AYAs more frequently had a normal BMI (79% vs 20%, P < .0001), we conducted separate analyses in each BMI group. We found excellent OS among younger and older (30-50 years) AYAs with normal BMI (4-year OS, 83% vs 85%, P = .89). Conversely, in AYAs who were overweight/obese, worse outcomes were seen in older AYAs (4-year OS, 55% vs 73%, P = .023). Regarding toxicity, AYAs who were overweight/obese experienced higher rates of grade 3/4 hepatotoxicity and hyperglycemia (60.7% vs 42.2%, P = .0005, and 36.4% vs 24.4%, P = .014, respectively) but had comparable rates of hypertriglyceridemia (29.5% vs 24.4%, P = .29). In a multivariable analysis, higher BMI was associated with worse OS, hypertriglyceridemia was associated with improved OS, and age was not associated with OS. In conclusion, among AYAs treated on DFCI Consortium ALL regimens, elevated BMI was associated with increased toxicity, increased NRM, and decreased OS. The deleterious effect of elevated BMI was more pronounced in older AYAs.

Multicenter Phase I Trial of Ivosidenib as Maintenance Treatment Following Allogeneic Hematopoietic Cell Transplantation for IDH1-Mutated Acute Myeloid Leukemia.

PURPOSE: Isocitrate dehydrogenase 1 (IDH1) mutations occur in 5% to 10% of patients with acute myeloid leukemia (AML). Ivosidenib is an IDH1 inhibitor, approved for use in patients with IDH1-mutated AML. PATIENTS AND METHODS: We conducted a multicenter, phase I trial of maintenance ivosidenib following allogeneic hematopoietic cell transplantation (HCT) in patients with IDH1-mutated AML. Ivosidenib was initiated between days 30 and 90 following HCT and continued for up to 12 28-day cycles. The first dose level was 500 mg daily, with level reduction to 250 mg daily, if needed, in a 3 × 3 de-escalation design. Ten additional patients would then receive the MTD or recommended phase 2 dose (RP2D). The primary endpoint was establishing the MTD or RP2D of ivosidenib. RESULTS: Eighteen patients were enrolled, of whom 16 initiated post-HCT ivosidenib. One dose-limiting toxicity, grade(g) 3 QTc prolongation, was observed. The RP2D was established at 500 mg daily. Attributable g≥3 adverse events were uncommon, with the most common being QTc prolongation in 2 patients. Eight patients discontinued maintenance, with only one due to adverse event. Six-month cumulative incidence (CI) of gII-IV aGVHD was 6.3%, and 2-year CI of all cGVHD was 63%. Two-year CI of relapse and nonrelapse mortality (NRM) were 19% and 0%, respectively. Two-year progression-free (PFS) was 81%, and 2-year overall survival (OS) was 88%. CONCLUSIONS: Ivosidenib is safe and well-tolerated as maintenance therapy following HCT. Cumulative incidence of relapse and NRM, as well as estimations of PFS and OS, were promising in this phase I study.

Current landscape of translational and clinical research in myelodysplastic syndromes/neoplasms (MDS): Proceedings from the 1st International Workshop on MDS (iwMDS) Of the International Consortium for MDS (icMDS).

Biological events that contribute to the pathogenesis of myelodysplastic syndromes/neoplasms (MDS) are becoming increasingly characterized and are being translated into rationally designed therapeutic strategies. Herein, we provide updates from the first International Workshop on MDS (iwMDS) of the International Consortium for MDS (icMDS) detailing recent advances in understanding the genetic landscape of MDS, including germline predisposition, epigenetic and immune dysregulation, the complexities of clonal hematopoiesis progression to MDS, as well as novel animal models of the disease. Connected to this progress is the development of novel therapies targeting specific molecular alterations, the innate immune system, and immune checkpoint inhibitors. While some of these agents have entered clinical trials (e.g., splicing modulators, IRAK1/4 inhibitors, anti-CD47 and anti-TIM3 antibodies, and cellular therapies), none have been approved for MDS. Additional preclinical and clinical work is needed to develop a truly individualized approach to the care of MDS patients.

Consensus proposal for revised International Working Group 2023 response criteria for higher-risk myelodysplastic syndromes.

Myelodysplastic syndromes/myelodysplastic neoplasms (MDS) are associated with variable clinical presentations and outcomes. The initial response criteria developed by the International Working Group (IWG) in 2000 have been used in clinical practice, clinical trials, regulatory reviews, and drug labels. Although the IWG criteria were revised in 2006 and 2018 (the latter focusing on lower-risk disease), limitations persist in their application to higher-risk MDS (HR-MDS) and their ability to fully capture the clinical benefits of novel investigational drugs or serve as valid surrogates for longer-term clinical end points (eg, overall survival). Further, issues related to the ambiguity and practicality of some criteria lead to variability in interpretation and interobserver inconsistency in reporting results from the same sets of data. Thus, we convened an international panel of 36 MDS experts and used an established modified Delphi process to develop consensus recommendations for updated response criteria that would be more reflective of patient-centered and clinically relevant outcomes in HR-MDS. Among others, the IWG 2023 criteria include changes in the hemoglobin threshold for complete remission (CR), the introduction of CR with limited count recovery and CR with partial hematologic recovery as provisional response criteria, the elimination of marrow CR, and specific recommendations for the standardization of time-to-event end points and the derivation and reporting of responses. The updated criteria should lead to a better correlation between patient-centered outcomes and clinical trial results in an era of multiple emerging new agents with novel mechanisms of action.

Novel immune directed therapies in myelodysplastic syndromes and acute myeloid leukemia.

PURPOSE OF REVIEW: Therapies that target the immune system are increasingly used across oncology, including in hematologic malignancies such as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). While allogeneic transplant has been a key therapy in these cancers, new approaches that target the immune system are being explored including immune checkpoint therapies, antibody-drug conjugates, and cellular therapies. RECENT FINDINGS: This review outlines updates in the preclinical rationale for immune directed therapies in MDS and AML, as well as recent clinical trials exploring these therapies. This manuscript summarizes the development of therapies targeting T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) and CD47, which are being evaluated in late phase studies in MDS and AML. It also reviews the landscape of other immune based therapies including antibody-drug conjugates, chimeric antigen receptor-T cells, bispecific antibodies, and tumor vaccines. SUMMARY: The treatment landscape in MDS and AML is rapidly changing; with a goal of improving the quality and duration of responses, a number of immune based therapies are under investigation. This review outlines recent advances with these therapies as well as some of the challenges that remain to incorporate them into leukemia care.

Psychological mobile app for patients with acute myeloid leukemia: A pilot randomized clinical trial.

BACKGROUND: Patients with acute myeloid leukemia (AML) experience a substantial decline in quality of life (QoL) and mood during their hospitalization for intensive chemotherapy, yet few interventions have been developed to enhance patient-reported outcomes during treatment. METHODS: We conducted a pilot randomized trial (ClinicalTrials.gov identifier NCT03372291) of DREAMLAND, a psychological mobile application for patients with a new diagnosis of AML who are receiving intensive chemotherapy. Patients were randomly assigned to DREAMLAND or usual care. DREAMLAND included four required modules focused on: (1) supportive psychotherapy to help patients deal with the initial shock of diagnosis, (2) psychoeducation to manage illness expectations, (3) psychosocial skill-building to promote effective coping, and (4) self-care. The primary end point was feasibility, which was defined as ≥60% of eligible patients enrolling and 60% of those enrolled completing ≥60% of the required modules. We assessed patient QoL (the Functional Assessment of Cancer Therapy-Leukemia), psychological distress (the Hospital Anxiety and Depression Scale and the Patient Health Questionnaire-9), symptom burden (the Edmonton Symptom Assessment Scale), and self-efficacy (the Cancer Self-Efficacy Scale) at baseline and at day 20 after postchemotherapy. RESULTS: We enrolled 60 of 90 eligible patients (66.7%), and 62.1% completed ≥75% of the intervention modules. At day 20 after chemotherapy, patients who were randomized to DREAMLAND reported improved QoL scores (132.06 vs. 110.72; p =.001), lower anxiety symptoms (3.54 vs. 5.64; p = .010) and depression symptoms (Hospital Anxiety and Depression Scale: 4.76 vs. 6.29; p = .121; Patient Health Questionnaire-9: 4.62 vs. 8.35; p < .001), and improved symptom burden (24.89 vs. 40.60; p = .007) and self-efficacy (151.84 vs. 135.43; p = .004) compared with the usual care group. CONCLUSIONS: A psychological mobile application for patients with newly diagnosed AML is feasible to integrate during hospitalization for intensive chemotherapy and may improve QoL, mood, symptom burden, and self-efficacy.

Nelarabine combination therapy for relapsed or refractory T-cell acute lymphoblastic lymphoma/leukemia.

Nelarabine, an antimetabolite prodrug, is approved as monotherapy for children and adults with relapsed and refractory T-cell acute lymphoblastic leukemia and lymphoma (R/R T-ALL/LBL), although it is often used in combination regimens. We sought to understand differences in efficacy and toxicity when nelarabine is administered alone or in combination. We retrospectively analyzed 44 consecutive patients with R/R T-ALL/LBL; 29 of whom were treated with combination therapy, most with cyclophosphamide and etoposide (23, 79%) and 15 with monotherapy. The median age was 19 years (range, 2-69), including 18 children (<18 years). After a median of 1 (range, 1-3) cycle of treatment, 24 patients (55%) achieved complete remission, 62% (18/29) with combination therapy and 40% (6/15) with monotherapy (P = .21). Most responders (21, 88%) pursued allogeneic stem cell transplant (alloSCT). Overall survival (OS) was 12.8 months (95% confidence interval, 6.93-not reached) in the entire cohort and was higher in the combination therapy than in the monotherapy group (24-month OS, 53% vs 8%; P = .003). The rate of neurotoxicity was similar between groups (27% vs 17%; P = .46) and grade 3/4 anemia and thrombocytopenia were more frequent in the combination group (76% vs 20%; P < .001% and 66% vs 27%; P = .014, respectively). In a multivariate analysis, nelarabine combination therapy and alloSCT post nelarabine were associated with improved OS (hazard ratio, 0.41; P = .04 and hazard ratio, 0.25; P = .008, respectively). In conclusion, compared with monotherapy, nelarabine combination therapy was well tolerated and associated with improved survival in pediatric and adult patients with R/R T-ALL/LBL.

Hematopoietic Cell Transplantation in the Management of Myelodysplastic Syndrome: An Evidence-Based Review from the American Society for Transplantation and Cellular Therapy Committee on Practice Guidelines.

The sole curative therapy for myelodysplastic syndrome (MDS) is allogeneic hematopoietic cell transplantation (HCT). Here this therapeutic modality is reviewed and critically evaluated in the context of the evidence. Specific criteria were used for searching the published literature and for grading the quality and strength of the evidence and the strength of the recommendations. A panel of MDS experts comprising transplantation and nontransplantation physicians developed consensus treatment recommendations. This review summarizes the standard MDS indications for HCT and addresses areas of controversy. Recent prospective trials have confirmed that allogeneic HCT confers survival benefits in patients with advanced or high-risk MDS compared with nontransplantation approaches, and the use of HCT is increasing in older patients with good performance status. However, patients with high-risk cytogenetic or molecular mutations remain at high risk for relapse. It is unknown whether administration of novel therapies before or after transplantation may decrease the risk of disease relapse in selected populations. Ongoing and future studies will investigate revised approaches to disease risk stratification, patient selection, and post-transplantation approaches to optimize allogeneic HCT outcomes for patients with MDS.

Comparison of demographics, disease characteristics, and outcomes between Black and White patients with myelodysplastic syndromes: A population-based study.

Racial disparities in cancer care and outcomes have been well documented in various malignancies, with Black patients having the highest death rate and shortest survival of any racial/ethnic group in the United States (US) for most cancers. However, there have been limited studies on racial/ethnic disparities in myelodysplastic syndromes (MDS). Our study characterized and compared differences in baseline demographics, clinical characteristics, socioeconomic factors, and overall survival (OS) between Black and White patients with MDS in the US. We used the Surveillance, Epidemiology, and End Results (SEER) Program and included 37,562 patients (Black, 8.1 %; White, 91.9 %) diagnosed between 2001 and 2013. We observed significant differences in baseline characteristics between cohorts. In a univariate analysis, Black race was associated with longer survival (hazard ratio [HR]: 0.83; 95 % confidence interval [CI], 0.79-0.86; p < 0.001). The association between race and survival was attenuated but remained significant in various models to adjust for differences in baseline characteristics (HR in multivariable analysis, 0.92; 95 % CI, 0.87-0.96); p < 0.001). Subgroup analysis by histology revealed differences in the association between race and OS. Refractory anemia (RA), RA with ring sideroblasts, and MDS-not otherwise specified, a category in SEER representing a poorly defined MDS subset for 52 % of cases in our study, favored Black patients. RA with excess blasts favored White patients. The overall finding that Black race is associated with better OS outcomes, when compared with White patients, needs to be interpreted with caution and nuanced by histology. Additional research to explore these associations is warranted.