Hematology/oncology Clinics of North America

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The advent of chimeric antigen receptor (CAR)-T cell therapy has revolutionized the treatment of several hematological malignancies. Although the initial benefit was mainly observed in aggressive leukemias and lymphomas, recent data have resulted in the approval of multiple CAR-T therapies in indolent lymphomas, with ongoing research showing great promise for further improvements and therapeutic optimizations. In this article, we review the published data and approved therapies for CAR-T cell therapy for indolent lymphomas focusing on mantle cell lymphoma and follicular lymphoma while describing the work in chronic lymphocytic leukemia and future strategies...

In locally advanced RCC, 6 phase 3 randomized controlled trials (RCTs) were designed in the perioperative setting with immune checkpoint inhibitor (ICI) monotherapy or combinations. Adjuvant trials with atezolizumab, pembrolizumab, and nivolumab with ipilimumab reported results, as did the only perioperative trial with nivolumab. Of these, only 1 year of adjuvant pembrolizumab improved disease-free survival (DFS) versus placebo, with the other trials showing no improvement in DFS. In the purely neoadjuvant setting, phase 1 b/2 ICI trials have demonstrated safety, efficacy, and dynamic changes of immune infiltrates, and provide a rationale for randomized trial concepts...

Inequity exists along the continuum of cancer and cancer care delivery in the United States. Marginalized populations have later stage cancer at diagnosis, decreased likelihood of receiving cancer-directed care, and worse outcomes from treatment. These inequities are driven by historical, structural, systemic, interpersonal, and internalized factors that influence cancer across the pathologic and clinical continuum. To ensure equity in cancer care, interventions are needed at the level of policy, care delivery, interpersonal communication, diversity within the clinical workforce, and clinical trial accessibility and design...

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Our international partnerships have fostered longstanding collaborative relationships leading to the development of unique, locally-designed, and sustainable training programs that serve as models for global health education and cooperation.

Lifestyle factors play a major role in the risk of breast cancer. This review aimed to examine the size of the effect of select lifestyle factors on risk for breast cancer and assess the quality of existing evidence. The authors performed an umbrella review of systematic reviews. The authors found an increased risk for breast cancer associated with obesity, alcohol intake, and smoking and a decreased risk due to physical activity. The evidence for sleep disruption and duration indicates risk for breast cancer, but it is limited in size, statistical significance, and quality of evidence...

Central America and the Caribbean is a highly heterogeneous region comprising more than 30 countries and territories with more than 200 million inhabitants. Although recent advances in the region have improved access to cancer care, there are still many disparities and barriers for obtaining high-quality cancer treatments, particularly for those from disadvantaged populations, immigrants, and rural areas. In this article, we provide an overview of cancer care in Central America and the Caribbean, with selected examples of issues related to disparities in access to care and suggest solutions and strategies to move forward...

CAR T cell therapy has significantly shaped the treatment landscape for refractory hematologic malignancies including large B-cell lymphomas, multiple myeloma, and leukemias. While response rates for a previously dismal prognosis have improved, certain obstacles still remain to achieving CAR T infallibility. In this article, we review the data surrounding proposed resistance mechanisms of tumors to CAR T, including the implications of target loss, exhausted T cells as effete effectors, the necessity of maximal CAR T expansion to durable response, the negative impact of an inflammatory milieu and a suppressive tumor microenvironment, and the optimal tumor-to-effector ratio that associates with best outcomes...

Climate change is the greatest threat to human health of our time, with significant implications for global cancer control efforts. The changing frequency and behavior of climate-driven extreme weather events results in more frequent and increasingly unanticipated disruptions in access to cancer care. Given the significant threat that climate change poses to cancer control efforts, oncology professionals should champion initiatives that help protect the health and safety of patients with cancer, such as enhancing emergency preparedness and response efforts and reducing emissions from our own professional activities, which has health cobenefits for the entire population...

Waldenström macroglobulinemia is an indolent IgM-secreting B-cell lymphoplasmacytic lymphoma that is preceded by an asymptomatic stage. Clinical and molecular features have been used in risk models to predict progression rates in different asymptomatic subgroups. Risk models used both disease-specific and nonspecific biomarkers for asymptomatic patients. Recently, models that incorporate continuous variables rather than distinct cutoffs have emerged to more accurately predict the risk of progression. Integrating genetic alterations to the clinical models is a promising approach that could improve risk stratification and management of asymptomatic patients...

Multiple myeloma is the second most common hematological malignancy with an approximate incidence of up to 8.5 cases per 100,000 persons per year. Over the last decade, therapy for multiple myeloma has undergone a revolutionary change. Chimeric antigen receptor (CAR) T-cell therapy has played a major role in this evolution. In this review, we discuss the existing state of CAR T-cell therapy in myeloma while evaluating several newer therapies and targets expected in the near future.

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This study investigated whether combining International Ovarian Tumor Analysis (IOTA) Simple Rules with tumor biomarkers would improve the diagnostic accuracy for early detection of adnexal malignancies. Receiver operating characteristic curve analysis of suspected adnexal tumors was performed in 226 women admitted for surgery at the University Clinical Center of Kosovo. Primary outcome was the diagnostic accuracy of the combination of adnexal mass biomarkers and IOTA Simple Rules. IOTA Simple Rules combined with biomarker indications increased the diagnostic accuracy of classifying adnexal masses...

The immunoglobulin M (IgM)-associated peripheral neuropathies (PN) are a heterogeneous group of disorders representing most paraproteinemic neuropathy cases. They are associated with IgM monoclonal gammopathy of undetermined significance (MGUS) or Waldenström macroglobulinemia. Establishing a causal link between a paraprotein and neuropathy can be challenging but is necessary to adopt an appropriate therapeutic approach. The most common type of IgM-PN is Antimyelin-Associated-Glycoprotein neuropathy, but half of the cases are of other causes...

Despite substantial progress in the clinical management of Waldenström's Macroglobulinemia (WM) and the emergence of chemotherapy-free approaches such as BTK inhibitors, WM is still a disease in which current treatments fail to cure and are in part associated with significant toxicities, compromising treatment outcome and quality of life. Thus, the vision for future front-line therapy should be to develop regimens which combine improved efficacy and excellent applicability with a low toxicity profile. Conventional immunochemotherapy such as bendamustine-rituximab is highly active but limited by hematotoxicity and long-lasting immunosuppression...

Bing-Neel syndrome is a rare manifestation of Waldenström macroglobulinemia (WM), which is caused by infiltration of the malignant lymphoplasmacytic cells in the central nervous system. Patients can present with a diverse range of neurologic symptoms, and differentiation with other comorbidities seen in WM, such as immunoglobulin M-related polyneuropathy, can be challenging. Both the rarity of this disorder and the heterogeneity of the clinical presentation often cause a significant diagnostic delay with the risk of permanent neurologic damage...

Waldenström's macroglobulinemia (WM) is an immunoglobulin M monoclonal gammopathy produced by a bone marrow lymphoplasmacytic lymphoma, an indolent non-Hodgkin lymphoma in which the cure is still an unmet challenge. Combinations with alkylating agents, purine analogs, and monoclonal antibodies, Bruton tyrosine kinase, and proteasome inhibitors are used for the treatment of relapsed and refractory patients. Moreover, new additional agents can be seen on the horizon as potential effective therapies. No consensus on a preferred treatment in the relapsed setting is available yet...

The discovery of MYD88 (L265P) mutation led to investigating BTK inhibitors in Waldenström macroglobulinemia (WM). Ibrutinib, the first-in-class agent, was approved based on a phase II trial in relapsed/refractory patients. In the phase III iNNOVATE study, the combination of rituximab and ibrutinib was compared with rituximab and placebo in treatment-naïve and relapsed/refractory patients. Second-generation BTK inhibitor, zanubrutinib, was compared with Ibrutinib in MYD88-mutated WM patients in the phase III ASPEN trial, whereas acalabrutinib was investigated in a phase II trial...

Histologic transformation (HT) to diffuse large B-cell lymphoma occurs rarely in Waldenström macroglobulinemia, with higher incidence in MYD88 wild-type patients. HT is suspected clinically when rapidly enlarging lymph nodes, elevated lactate dehydrogenase levels, or extranodal disease occur. Histologic assessment is required for diagnosis. HT carries a worse prognosis compared with nontransformed Waldenström macroglobulinemia. A validated prognostic score based on three adverse risk factors stratifies three risk groups...