Author
Jonathan Webster
Bio: Jonathan Webster is an academic researcher from Johns Hopkins University. The author has contributed to research in topics: Medicine & Myeloid leukemia. The author has an hindex of 7, co-authored 20 publications receiving 183 citations.
Papers
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TL;DR: Low-intensity combination therapy response rates appear to be approaching that of induction regimens, and with lower toxicity, low-intensity therapy likely represents the future standard approach in this age group.
Abstract: Acute myeloid leukemia (AML) therapies are rapidly evolving with novel targeted therapies showing high-level responses in a notoriously difficult to treat group of patients – the elderly and unfit. This review will examine the outcomes of older AML patients (>60 years old) with conventional induction strategies, and published literature on risks of pursuit of induction. Low-intensity combination therapy response rates appear to be approaching that of induction regimens, and with lower toxicity, low-intensity therapy likely represents the future standard approach in this age group. Lastly, allogeneic transplant appears to have a role in increasing durable remissions regardless of age and should be considered in patients with limited comorbidities.
47 citations
TL;DR: It is concluded that pharmacologic thromboprophylaxis is frequently administered to hospitalized patients with cancer but that nearly one third of patients are considered to have relative contraindications for prophylactic anticoagulation.
Abstract: Purpose Hospitalized patients with cancer are considered to be at high risk for venous thromboembolism (VTE). Despite strong recommendations in numerous clinical practice guidelines, retrospective studies have shown that pharmacologic thromboprophylaxis is underutilized in hospitalized patients with cancer. Patients and Methods We conducted a prospective, cross-sectional study of hospitalized patients with cancer at five academic hospitals to determine prescription rates of thromboprophylaxis and factors influencing its use during hospitalization. Results A total of 775 patients with cancer were enrolled across five academic medical centers. Two hundred forty-seven patients (31.9%) had relative contraindications to pharmacologic prophylaxis. Accounting for contraindications to anticoagulation, the overall rate of pharmacologic thromboprophylaxis was 74.2% (95% CI, 70.4% to 78.0%; 392 of 528 patients). Among the patients with cancer without contraindications for anticoagulation, individuals hospitalized wi...
45 citations
TL;DR: To assess safety and response to AZA/Pembro after minimum 2 cycles of therapy in relapsed/refractory AML and newly diagnosed (dx) older AML, patients with prior allogeneic stem cell transplant (alloSCT) were included and Cohort 2 started enrollment.
44 citations
TL;DR: Responsibility rates and survival were similar between the two groups in spite of evidence that MK-8776 augmented DNA damage in circulating leukemic blasts, and better than expected results in the control arm using timed sequential AraC and truncated patient enrollment may have limited the ability to detect clinical benefit from the combination.
38 citations
TL;DR: Early results of a multi-center phase I study combining blinatumomab with monoclonal antibodies targeting PD-1 (nivolumab) +/- CTLA-4 (ipilimumab) in R/R CD19+ ALL show blockade of co-inhibitory pathways represents a viable strategy to enhance blinatonomab efficacy.
30 citations
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TL;DR: The current bispecific antibody landscape is reviewed from a mechanistic perspective, including a comprehensive overview of the pipeline, to have the potential for novel functionalities that are not provided by mixtures of monoclonal antibodies.
Abstract: The term bispecific antibody (bsAb) is used to describe a large family of molecules designed to recognize two different epitopes or antigens. BsAbs come in many formats, ranging from relatively small proteins, merely consisting of two linked antigen-binding fragments, to large immunoglobulin G (IgG)-like molecules with additional domains attached. An attractive bsAb feature is their potential for novel functionalities - that is, activities that do not exist in mixtures of the parental or reference antibodies. In these so-called obligate bsAbs, the physical linkage of the two binding specificities creates a dependency that can be temporal, with binding events occurring sequentially, or spatial, with binding events occurring simultaneously, such as in linking an effector to a target cell. To date, more than 20 different commercialized technology platforms are available for bsAb creation and development, 2 bsAbs are marketed and over 85 are in clinical development. Here, we review the current bsAb landscape from a mechanistic perspective, including a comprehensive overview of the pipeline.
654 citations
TL;DR: The authors, a group with expertise in the clinical, pathologic and genetic aspects of these disorders, developed the International Consensus Classification (ICC), aimed at facilitating diagnosis and prognostication of these neoplasms, improving treatment of affected patients, and allowing the design of innovative clinical trials.
444 citations
TL;DR: Practical guidance is offered on how to prevent, diagnose, and treat venous thromboembolism (VTE) in cancer patients, and the management of "challenging" cases of VTE is discussed.
Abstract: Venous thromboembolism (VTE), including deep-vein thrombosis and pulmonary embolism, represents a major cause of morbidity and mortality in cancer patients. Patients with cancer are six times more likely to develop VTE than their noncancer counterparts, and VTE is the second leading cause of death in cancer patients. Despite the publication of major consensus guidelines setting out recommendations for thromboprophylaxis in cancer patients, there remains a gulf between these guidelines and clinical practice. In general, thromboprophylaxis is recommended for most patients hospitalized with active cancer. Furthermore, outpatient thromboprophylaxis may be used in carefully selected high-risk ambulatory patients. Certain areas of controversy still remain. Although low-molecular-weight heparin has been shown to be superior to vitamin K antagonists in cancer patients, the role of direct oral anticoagulants is still uncertain. Moreover, recurrent thromboembolism, bleeding, and thrombocytopenia are frequently seen in cancer patients. Optimal anticoagulation in such instances presents a major challenge to clinicians. Modern computed tomography techniques have resulted in an increase in the detection of "incidental" VTE. Despite a growing body of evidence promulgating standard anticoagulant treatment in such cases, these cases present further challenges for members of the multidisciplinary team. The Oncologist 2017;22:199-207Implications for Practice: This article discusses venous thromboembolism (VTE) in patients with malignancy. Practical guidance is offered on how to prevent, diagnose, and treat VTE in cancer patients. The management of "challenging" cases of VTE is also discussed.
149 citations
01 Mar 2020
TL;DR: The use of ‘immunocompatible’ cytotoxic drugs combined with anti-PD-(L)1 antibodies is a modern approach, not only for increasing the direct killing of cancer cells, but also as a strategy to minimize the activation of immunosuppressive and cancer cell prosurvival program responses.
Abstract: Monoclonal antibodies targeting programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) immune checkpoints have improved the treatments of cancers. However, not all patients equally benefit from immunotherapy. The use of cytotoxic drugs is practically inevitable to treat advanced cancers and metastases. The repertoire of cytotoxics includes 80 products that principally target nucleic acids or the microtubule network in rapidly proliferating tumor cells. Paradoxically, many of these compounds tend to become essential to promote the activity of immunotherapy and to offer a sustained therapeutic effect. We have analyzed each cytotoxic drug with respect to effect on expression and function of PD-(L)1. The major cytotoxic drugs—carboplatin, cisplatin, cytarabine, dacarbazine, docetaxel, doxorubicin, ecteinascidin, etoposide, fluorouracil, gemcitabine, irinotecan, oxaliplatin, paclitaxel and pemetrexed—all have the capacity to upregulate PD-L1 expression on cancer cells (via the generation of danger signals) and to promote antitumor immunogenicity, via activation of cytotoxic T lymphocytes, maturation of antigen-presenting cells, depletion of immunosuppressive regulatory T cells and/or expansion of myeloid-derived suppressor cells. The use of ‘immunocompatible’ cytotoxic drugs combined with anti-PD-(L)1 antibodies is a modern approach, not only for increasing the direct killing of cancer cells, but also as a strategy to minimize the activation of immunosuppressive and cancer cell prosurvival program responses.
123 citations