The classification of myeloid neoplasms and acute leukemias was last updated in 2016 within a collaboration between the World Health Organization (WHO), the Society for Hematopathology, and the ...European Association for Haematopathology. This collaboration was primarily based on input from a clinical advisory committees (CACs) composed of pathologists, hematologists, oncologists, geneticists, and bioinformaticians from around the world. The recent advances in our understanding of the biology of hematologic malignancies, the experience with the use of the 2016 WHO classification in clinical practice, and the results of clinical trials have indicated the need for further revising and updating the classification. As a continuation of this CAC-based process, the authors, a group with expertise in the clinical, pathologic, and genetic aspects of these disorders, developed the International Consensus Classification (ICC) of myeloid neoplasms and acute leukemias. Using a multiparameter approach, the main objective of the consensus process was the definition of real disease entities, including the introduction of new entities and refined criteria for existing diagnostic categories, based on accumulated data. The ICC is aimed at facilitating diagnosis and prognostication of these neoplasms, improving treatment of affected patients, and allowing the design of innovative clinical trials.
Progress in the understanding of the biology and therapy of acute myeloid leukemia (AML) is occurring rapidly. Since 2017, nine agents have been approved for various indications in AML. These ...included several targeted therapies like venetoclax, FLT3 inhibitors, IDH inhibitors, and others. The management of AML is complicated, highlighting the need for expertise in order to deliver optimal therapy and achieve optimal outcomes. The multiple subentities in AML require very different therapies. In this review, we summarize the important pathophysiologies driving AML, review current therapies in standard practice, and address present and future research directions.
Recent years have witnessed major advances that have improved outcome of adults with acute lymphoblastic leukemia (ALL). The emergence of the concept of measurable residual disease has fine-tuned our ...prognostic models and guided our treatment decisions. The treatment paradigms of ALL have been revolutionized with the advent of tyrosine kinase inhibitors targeting BCR-ABL1, monoclonal antibodies targeting CD20 (rituximab), antibody-drug conjugates targeting CD22 (inotuzumab ozogamicin), bispecific antibodies (blinatumomab), and CD19 chimeric antigen receptor T cell therapy (tisagenlecleucel). These highly effective new agents are allowing for novel approaches that reduce reliance on intensive cytotoxic chemotherapy and hematopoietic stem cell transplantation in first remission. This comprehensive review will focus on the recent advances and future directions in novel therapeutic strategies in adult ALL.
Background
Several important treatment and supportive care strategies have been implemented over the past 4 decades in the management of acute myeloid leukemia (AML).
Methods
The authors identified ...29,107 patients who were diagnosed with de novo AML between 1980 and 2017 in the National Cancer Institute's Surveillance, Epidemiology, and End Results database. Patients were categorized into 5 age groups (ages birth to 14, 15‐39, 40‐59, 60‐69, and ≥70 years) and 4 calendar periods (1980‐1989, 1990‐1999, 2000‐2009, and 2010‐2017). The outcomes of patients who had AML within these categories were analyzed.
Results
The overall 5‐year survival rates in patients with AML were 9%, 15%, 22%, and 28% in the decades 1980 to 1989, 1990 to 1999, 2000 to 2009, and 2010 to 2017, respectively. Among patients aged 15 to 39 years, the 5‐year survival rates were 24%, 41%, 52%, and 63%, respectively; among those aged ≥70 years, the 5‐year survival rates were 1%, 2%, 3%, and 5%, respectively. Four‐week mortality was surprising high among adults and older patients (range, 20%‐45%), even in modern times. Overall, survival continued to improve over the calendar periods and was best in the period from 2010 to 2017. Survival improvement was noticeable across all age groups except patients aged ≥70 years, in whom the estimated 5‐year survival rate remained 5% even during the period from 2010 to 2017.
Conclusions
The outcomes of patients with AML showed incremental improvement over time in a population‐based study of the Surveillance, Epidemiology, and End Results data. The introduction since 2017 of targeted therapies among older patients and optimizations in supportive care hopefully will continue to improve outcomes in AML, particularly among older patients.
The outcome of patients with acute myeloid leukemia demonstrates incremental improvement over time in a population‐based study of the National Cancer Institute's Surveillance, Epidemiology, and End Results data. For older patients with acute myeloid leukemia, the introduction since 2017 of targeted therapies and optimizations in supportive care hopefully will continue to improve outcomes.
Older patients with acute lymphoblastic leukemia (ALL) have historically had poor outcomes (5-year survival rate, 20%) with standard intensive and dose-adjusted chemotherapy regimens, due to a high ...incidence of adverse biologic features including high-risk cytogenetics, presence of
TP53
mutations, and poor tolerance to intensive therapy. Thus, there is an unmet medical need in this patient population. Inotuzumab ozogamicin is a humanized antibody–drug conjugate that targets CD22-positive leukemic blasts. It is approved for the treatment of relapsed or refractory ALL and has been shown to be effective and tolerable in older patients. Several ongoing trials in older patients with newly diagnosed ALL have yielded encouraging data with inotuzumab ozogamicin in induction alone and in combination with low-intensity chemotherapy. In this podcast, the authors summarize and highlight some of the recent findings on the use of inotuzumab ozogamicin as induction therapy for older adults with newly diagnosed ALL.
Summary
The past decade has witnessed tremendous progress in the treatment of acute lymphoblastic leukaemia (ALL), primarily due to the development of targeted therapies, including tyrosine kinase ...inhibitors targeting BCR‐ABL1 tyrosine kinase, monoclonal antibodies targeting cell surface antigens (CD19, CD20 and CD22), bispecific antibodies and chimeric antigen receptor T‐ cell therapy. A number of new therapies have been approved by the US Food and Drug Administration in the past 5 years, including blinatumomab in 2014, inotuzumab ozagamicin in 2017 and tisagenlecleucel in 2017 for relapsed/refractory ALL. This has led to tremendous improvement in long‐term survival, of more than 50% in patients with precursor B‐ALL 50–70% in patients with Philadelphia chromosome (Ph)‐positive ALL), 50–60% in T‐ALL and 80% in mature B‐ALL. Research is ongoing to optimize the benefit of targeted therapeutics with the goal of decreasing the use of cytotoxic therapies.
Abstract Although imatinib remains the gold standard for first-line treatment of chronic myeloid leukemia (CML), increasing recognition of imatinib resistance and intolerance has led to the ...development of additional tyrosine kinase inhibitors (TKIs), which have demonstrated effectiveness as salvage therapies or alternative first-line treatments. Although additional options represent progress, the availability of 3 second-generation TKIs (dasatinib, nilotinib, and bosutinib) and 1 third-generation TKI (ponatinib) has added complexity to the treatment paradigm for CML, particularly CML in the chronic phase. Two second-generation agents (dasatinib and nilotinib) are approved for use as first-line and subsequent therapy. Thus, the appropriate sequencing of TKIs is a frequent quandary, and is incompletely addressed in clinical guidelines. Here, we review studies that might guide selection of a second- or third-generation TKI after failure of TKI therapy in patients with chronic-phase CML. These studies evaluate prognostic factors such as first-line cytogenetic response and BCR-ABL1 mutation status, which might help physicians identify patients who are likely to respond to second-generation TKIs, and those for whom ponatinib or an investigational agent might be more appropriate. We summarize evidence to date that suggests that use of a second-generation TKI as third-line therapy confers limited value in most CML patients, and we also explore the utility of current event-free survival versus traditional outcomes to predict long-term benefits of sequential TKI use. Finally, we present 3 case studies to illustrate how prognostic factors and other considerations (eg, tolerability) can be used to individualize subsequent therapy in cases of TKI resistance or intolerance.
Despite significant improvements in the signs and symptoms of myelofibrosis (MF), and possible prolongation of patients' survival, some have disease that is refractory to ruxolitinib and many lose ...their response over time. Furthermore, patients with ≥3 mutations are less likely to respond to ruxolitinib. Here we describe outcomes after ruxolitinib discontinuation in MF patients enrolled in a phase 1/2 study at our center. After a median follow-up of 79 months, 86 patients had discontinued ruxolitinib (30 of whom died while on therapy). The median follow-up after ruxolitinib discontinuation for the remaining 56 patients was 32 months, with median survival after discontinuation of 14 months. Platelets <260 × 109/L at the start of therapy or <100 × 109/L at the time of discontinuation were associated with shorter survival after discontinuation. Of 62 patients with molecular data at baseline and follow-up, 22 (35%) acquired a new mutation while receiving ruxolitinib (14 61% in ASXL1). Patients showing clonal evolution had significantly shorter survival after discontinuation (6 vs 16 months). Transfusion dependency was the only clinical variable associated with clonal evolution. These findings underscore the need for novel therapies and suggest that clonal evolution or decreasing platelet counts while on ruxolitinib therapy may be markers of poor prognosis.
•Survival of patients with MF after ruxolitinib discontinuation is poor, with median survival of 14 months.•Low platelets at the start or end of therapy or clonal evolution while on therapy are associated with an even worse prognosis.
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