Low-dose decitabine plus venetoclax as post-transplant maintenance for high-risk myeloid malignancies.

Relapse remains a major cause of treatment failure following allogeneic stem cell transplantation (allo-SCT) for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We retrospectively investigated low-dose decitabine and venetoclax (DEC/VEN) as post-transplant maintenance in 26 older patients with AML and MDS. The cumulative incidence of day 100 gIII-IV acute graft versus host disease (GVHD) and 1-year moderate-severe chronic GVHD was 5% and 26%, respectively. One patient relapsed 14 m after transplant. The 1-year non-relapse mortality and survival were 11% and 84%, respectively. DEC/VEN is a safe and potentially effective strategy to reduce the risk of post-transplant relapse.

The impact of race and ethnicity on diffuse large B-cell lymphoma outcomes within the veterans health administration (VHA).

We performed a retrospective chart review of 6266 randomly selected DLBCL patients treated in the VHA nationwide between 1/1/2011 and 12/31/2021. The 3178 patients who met inclusion criteria were predominantly male (97%) and white (75%). Median age of diagnosis for Black patients was 63 years vs 69 years for the entire cohort (p < 0.001). However, patients in each race/ethnicity subgroup presented with similar rates of stage I/II and III/IV disease, IPI score, cell of origin and HIT status. Outcomes analysis revealed similar treatment, response rates, median overall survival, and 1-, 3-, and 5-year survival across all subgroups. Hispanic patients had a 21% lower risk of death (HR = 0.79) than white patients, and Black patients had no significant difference in survival (HR = 0.98). This large retrospective study shows that when standard of care therapy is given within an equal access system, short-term treatment and survival outcomes are the same for all races.

Addition of single dose gemtuzumab ozogamicin to intensive induction chemotherapy in core-binding factor acute myeloid leukemia.

In a meta-analysis of 5 trials, the addition of gemtuzumab ozogamicin (GO) to intensive induction chemotherapy led to a survival benefit in patients with core-binding factor (CBF) acute myeloid leukemia (AML). Given the heterogeneous incorporation of GO in clinical trials, the ideal dose and schedule remains unclear. We conducted a single-center retrospective analysis to compare outcomes of patients with CBF-AML treated with intensive induction chemotherapy, with or without a single dose of GO 3 mg/m2, during induction only. We included 87 patients (GO=32, control=55). The composite complete remission (cCR) rate was higher in the control group (93%) compared to the GO group (82%) (p<0.001). The rate of measurable residual disease (MRD) negative cCR, by flow cytometry, was similar between both groups. There were no significant differences between the two groups in terms of toxicity. The 3-year relapse-free survival (RFS) for both groups was similar (71% vs 68%, p=0.5). The 3-year overall survival (OS) for the GO group was 68%, compared to 66% for the control group (p=0.9).In multivariable analysis, age and MRD positive status were risk factors for inferior outcomes. We find that survival of patients with CBF-AML is favorable in the real-world setting. The addition of single-dose GO, during induction, did not lead to a higher remission rate or survival benefit, when compared to intensive chemotherapy without GO. Further investigation into the incorporation of GO in the treatment algorithm for CBF-AML is needed.

Factors Associated with Cancer Prevention/Risk Reduction Behaviors among Latinos.

Improving understanding of behaviors that increase or reduce cancer risk for different Hispanic groups is a public health priority; such knowledge is sparse in new gateway immigration locations such as Indiana. The aims of this study were to: 1) describe cancer beliefs and cancer preventive/risk reduction behaviors (physical activity, tobacco, and alcohol use) among Hispanic adults; 2) examine differences in cancer beliefs and preventive behaviors by country/territory of birth, socioeconomic status, and area of residence (urban vs. rural); and 3) determine predictors of engagement in cancer prevention and risk reduction behaviors in this population. A cross-sectional online survey targeted adult Indiana residents who identified as Latino, Hispanic, or Spanish recruited using Facebook-targeted advertising. Complete survey data from 1520 respondents were analyzed using descriptive, unadjusted, and adjusted models. The majority of respondents believed they were unlikely to get cancer but held many other fatalistic beliefs about cancer. Only 35.6% of respondents had received the HPV vaccine, 37.6% reported they were currently smoking cigarettes, and 64% reported occasional or frequent drinking of alcohol. Respondents spent an average of 3.55 days per week engaged in moderate exercise. Differences were observed by country/territory of birth, income, and education but not by rural residence status. Predictors of cancer risk/risk reduction behaviors were identified. The Hispanic population in Indiana is diverse and effective interventions for cancer prevention should be culturally targeted based on country/territory of birth and individually tailored based on cancer-related beliefs.

Thrombotic Events Are Unusual Toxicities of Chimeric Antigen Receptor T-Cell Therapies.

Chimeric antigen receptor (CAR) T-cell therapy has greatly transformed the treatment and prognosis of B-cell hematological malignancies. As CAR T-cell therapy continues to be more readily adopted and indications increase, the field's recognition of emerging toxicities will continue to grow. Among the adverse events associated with CAR T-cell therapy, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS) are the most common toxicities, while thrombotic events represent an under-reported, life-endangering complication. To determine thrombosis incidence post CAR T-cell therapy, we performed a multi-center, retrospective study on CAR T-cell therapy adult patients (N = 140) from Indiana University Simon Cancer Center and the University of North Carolina Medical Center treated from 2017 to 2022 for relapsed and refractory B-cell acute lymphoblastic leukemia (B-ALL, N = 3), diffuse large B-cell lymphoma (DLBCL, N = 92), follicular lymphoma (FL, N = 9), mantle cell lymphoma (MCL, N = 2), and multiple myeloma (MM, N = 34). We report 10 (7.14%) thrombotic events related to CAR T-cell therapy (DLBCL: N = 8, FL: N = 1, MM: N = 1) including 9 primary venous events and 1 arterial event that occurred with median time of 23.5 days post CAR T-cell infusion. In search of parameters associated with such events, we performed multivariate analyses of coagulation parameters (i.e., PT, PTT, and D-Dimer), scoring for adverse events (Padua Score and ISTH DIC Score) and grading for CAR T-cell toxicity severity (CRS grade and ICANS grade) and found that D-Dimer peak elevation and ICANS grade were significantly associated with post-CAR T-cell infusion thrombosis. While the pathophysiology of CAR T-cell associated coagulopathy remains unknown, our study serves to develop awareness of these emerging and unusual complications.

Cancer-related knowledge, beliefs, and behaviors among Hispanic/Latino residents of Indiana.

BACKGROUND: Cancer is the leading cause of death for Hispanics in the USA. Screening and prevention reduce cancer morbidity and mortality. METHODS: This study administered a cross-sectional web-based survey to self-identified Hispanic residents in the state of Indiana to assess their cancer-related knowledge, beliefs, and behaviors, as well as to identify what factors might be associated with cancer screening and prevention. Chi-square and Fisher's exact test were used to compare associations and logistic regression used to develop both univariate and multivariate regression models. RESULTS: A total of 1520 surveys were completed, median age of respondents was 53, 52% identified as men, 50.9% completed the survey in Spanish, and 60.4% identified the USA as their country of birth. Most were not able to accurately identify ages to begin screening for breast, colorectal, or lung cancer, and there were significant differences in cancer knowledge by education level. US-born individuals with higher income and education more often believed they were likely to develop cancer and worry about getting cancer. Sixty eight percent of respondents were up-to-date with colorectal, 44% with breast, and 61% with cervical cancer screening. Multivariate models showed that higher education, lack of fatalism, older age, lower household income, and unmarried status were associated with cervical cancer screening adherence. CONCLUSIONS: Among a Hispanic population in the state of Indiana, factors associated with cervical cancer screening adherence were similar to the general population, with the exceptions of income and marital status. Younger Hispanic individuals were more likely to be adherent with breast and colorectal cancer screening, and given the higher incidence of cancer among older individuals, these results should guide future research and targeted outreach.

A case report of the metagenomics next-generation sequencing for early detection of central nervous system mucormycosis with successful rescue in patient with recurrent chronic lymphocytic leukemia.

Background: Central nervous system (CNS) mucormycosis is insidious and difficult to diagnose. It progresses rapidly and causes high mortality. Rare cases have been reported during ibrutinib use, which have poor prognosis. Through this case, we share the experience of successful diagnosis and treatment. We also emphasize the importance of focusing on high-risk groups, early diagnosis and prompt management. Case Description: In this case, a 52-year-old patient was diagnosed with chronic lymphocytic leukemia (CLL) for more than 5 years. He was in remission after rituximab plus fludarabine and cyclophosphamide (RFC) regimen, and relapsed in the fourth year. During the ibrutinib monotherapy, the patient presented with sudden headache. Cranial imaging examination revealed a definite right occipitoparietal lobe mass with extensive edema. A rapid diagnosis of mucormycosis infection was made using metagenomic next-generation sequencing (mNGS). The patient at that time didn't have neutropenia, but he had hypogammaglobulinemia. The infection was treated with amphotericin B cholesteryl sulfate complex, posaconazole, and interventional surgery, and the treatment was successful. At the same time, we considered the control of disease progression in this relapsed patient with, as well as to the drug interaction with posaconazole. We chose the next generation Bruton's tyrosine kinase (BTK) inhibitor zanubrutinib as the treatment, whose safety has been identified. As of the submission date, the patient has been followed up for nearly 1 year, and his disease is stable. Conclusions: When new clinical problems arise in recurrent CLL patients, it is important to identify multiple factors, especially the insidious fungal infections. In particular, the immunocompromised patients should be concerned. CNS mucormycosis is extremely deadly, the early diagnosis will improve the prognosis. In clinical practice, the gold standard diagnosis of mucormycosis is difficult to obtain through pathology. In this case, mNGS was applied to quickly diagnose mucormycosis, enabling earlier treatment and ameliorating the prognosis. Thus, it will help us to early detect this group of people who may be potentially infected. Current guidelines do not recommend the prophylactic use of antifungal agents in treated CLL patients. However, in patients with prior severe infection or hypogammaglobulinemia, intravenous immunoglobulin is recommended to reduce the associated infection rate.

Immune-Based Therapeutic Interventions for Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is an aggressive, clonally heterogeneous, myeloid malignancy, with a 5-year overall survival of approximately 27%. It constitutes the most common acute leukemia in adults, with an incidence of 3-5 cases per 100,000 in the United States. Despite great advances in understanding the molecular mechanisms underpinning leukemogenesis, the past several decades had seen little change to the backbone of therapy, comprised of an anthracycline-based induction regimen for those who are fit enough to receive it, followed by risk-stratified post-remission therapy with consolidation cytarabine or allogeneic stem cell transplantation (allo-SCT). Allo-SCT is the most fundamental form of immunotherapy in which donor cytotoxic T and NK cells recognize and eradicate residual AML in the graft-versus-leukemia (GvL) effect. Building on that, several alternative or synergistic approaches to exploit both self and foreign immunity against AML have been developed. Checkpoint inhibitors, for example, CTLA-4 inhibitors, PD-1 inhibitors, and PD-L1 inhibitors block proteins found on T cells or cancer cells that stop the immune system from attacking the cancer cells. They have been used with limited success in both the AML relapsed/refractory (R/R) and post SCT settings. AML tumor mutational burden is low compared to solid tumors and thus, it is less likely to generate neoantigens and respond to antibody-mediated checkpoint blockade that has shown unprecedented results in solid tumors. Therefore, alternative therapeutic strategies that work independently of the T cell receptor (TCR) specificity have been developed. They include bispecific antibodies, which recruit T cells through CD3 engagement, and in AML have shown an overall response rate ranging between 14 and 30% in early phase trials. Chimeric Antigen Receptor (CAR) T cell therapy is a type of treatment in which T cells are genetically engineered to produce a recombinant receptor that redirects the specificity and function of T lymphocytes. However, lack of cell surface targets exclusively expressed on AML cells including Leukemic Stem Cells (LSCs) combined with clonal heterogeneity represents the biggest challenge in developing CAR therapy for AML. Antibody-Drug Conjugates (ADC) constitute the only FDA-approved immunotherapy to treat AML with Gemtuzumab Ozogamicin, a CD33-specific ADC used in CEBPα-mutated AML. The identification of additional cell surface targets is critical for the development of other ADC's potentially useful in the induction and maintenance regimens, given the ease at which these reagents can be generated and managed. Here, we will review those immune-based therapeutic interventions and highlight active areas of research investigations toward fulfillment of the great promise of immunotherapy to AML.

CD123-targeted therapy in acute myeloid leukemia.

INTRODUCTION: Acute myeloid leukemia (AML) results from the neoplastic transformation of a hematopoietic stem cell. While therapeutic progress has stagnated for several decades, recent progress in the genomic classification of AML has paved the way for multiple new drug approvals. These long-awaited achievements represent a paradigm shift in the approach to a disease that has largely been managed with conventional chemotherapy since the 1970s. With the evolution of targeted AML therapies, novel agents continue to be developed with the goal to improve efficacy while minimizing toxicity. Monoclonal antibodies targeting AML-specific surface markers have emerged as promising candidates to improve outcomes. CD123, interleukin-3 receptor alpha chain [IL-3 Rα], is highly expressed in AML, particularly within the AML stem cell compartment. Several CD123-targeted strategies are currently being evaluated in clinical trials. AREAS COVERED: The authors herein discuss recent clinical data in CD123-directed therapy in AML. A computerized PubMed search was conducted using key words relevant to the various sections of this article. Relevant abstracts presented at the American Society of Hematology, the European Hematology Association, and the American Society of Clinical Oncology were also reviewed. EXPERT OPINION: CD123 represents a suitable therapeutic target that has the potential to improve AML patient outcomes.

Outcomes in chronic lymphocytic leukemia patients on novel agents in the US Veterans Health Administration System.

The US veteran population has a high proportion of chronic lymphocytic leukemia (CLL) risk factors. Using the Veterans Health Administration (VHA) population, we conducted a retrospective chart review of 1205 CLL patients who initiated treatment with a novel oral agent. For 1L ibrutinib, 33% (n = 107) discontinued therapy during the study, of which 64% discontinued due to adverse events (AEs). For relapsed/refractory (R/R) ibrutinib, 35% (n = 262) discontinued therapy, of which 63% discontinued due to AEs. For R/R venetoclax, 31% (n = 27) discontinued therapy, of which 41% were due to AEs. For idelalisib, 84% (n = 41) discontinued therapy, of which 54% were due to AEs. This real-world study suggests that AEs play an important role in dose reductions and discontinuations; however, physician inexperience in using these drugs when they were first introduced could be part of what is leading to these negative outcomes.

West Nile Encephalitis, an Unusual Infection in a Chronic Lymphocytic Leukemia Patient.

CNS involvement by CLL is a rare occurrence, usually happening in the context of a transformation to a more aggressive lymphoma in what is known as Richter's transformation. We report a patient with active CLL who developed confusion and was found to have West Nile encephalitis that initially mimicked CNS involvement by CLL. The patient recovered with supportive treatment and later restarted ibrutinib therapy. This case illustrates the importance of maintaining a broad differential among cancer patients with new onset confusion as well as that of questioning malignant infiltration of CNS when there is concomitant active CNS infection.