Authors
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Targeting CD19 With CAR T in R/R DL B-Cell Lymphoma: Brian T. Hill, MD, PhD; Mazyar Shadman, MD, MPHDoctors from University of Washington and Cleveland Clinic discussed targeting CD19 in CAR T-cell therapy for relapsed/refractory DLBCL.
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FasTCAR Cell Therapy Granted Orphan Drug Designation for Multiple MyelomaThe designation follows durable responses seen in a phase 1 study of the agent.
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Dr. Sehgal on the Clinical Implications of CAR T-Cell Therapy in DLBCLAlison R. Sehgal, MD, assistant professor of medicine, hematologist/medical oncologist, University of Pittsburgh School of Medicine, UPMC Hillman Cancer Center, discusses the clinical implications of CAR T-cell therapy in diffuse large B-cell lymphoma (DLBCL).
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Dr. Hou on the Latest Updates With CAR T-Cell Therapy in DLBCLJing-Zhou Hou, MD, PhD, co-chair of the Hematological Malignancies program, and medical oncologist, hematologist, and clinical instructor at University of Pittsburgh Medical Center Hillman Cancer Center, discusses the latest updates with CAR T-cell therapy in diffuse large B-cell lymphoma (DLBCL).
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Outpatient CAR T-Cell Therapy Found Safe, Effective in Large B-Cell LymphomaCarlos R. Bachier, MD, discusses the use of CAR T-cell therapy in the outpatient setting. He also shared insight on the evolving paradigm of graft-versus-host disease.
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Dr. Mei on Investigational CAR T-Cell Therapies and Antibody-Drug Conjugates in Hodgkin LymphomaMatthew G. Mei, MD, assistant clinical professor, Department of Hematology and Hematopoietic Cell Transplantation, and hematologist/oncologist, City of Hope, discusses investigational CAR T-cell therapies and antibody-drug conjugates (ADCs) in Hodgkin lymphoma.
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Axi-cel as Frontline Therapy for High-Risk Large B-cell Lymphoma Produces Encouraging ResponsesIn 37 evaluable patients, the objective response rate in the study was 89% (95% CI, 75%-97%) with complete responses in 78%.
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Dr. Santomasso on Managing CNS Toxicity from CAR T-Cell Therapy for B-Cell LymphomaBianca D. Santomasso, MD, PhD, discusses how she prevents central nervous system toxicity due to CAR T-cell therapy for aggressive B-cell lymphoma in her own practice.
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Dr. Sotomayor on the Durability of CAR T Cells in Hematologic MalignanciesEduardo Sotomayor, MD, professor of medicine, Department of Hematology and Oncology, and director, GW Cancer Center, discusses the durability of CAR T cells, as well as ways to combat immune escape mechanisms in hematologic malignancies.
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Dr. Marasco on Engineering CAR T CellsWayne A. Marasco, MD, PhD, discusses ways CAR T cells are being engineered to avoid on-target adverse events in solid tumors.
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Dr. Shah on CAR T-Cell Therapy in Pediatric ALLNirali N. Shah, MD, MHSc, discusses the use of CAR T-cell therapy in pediatric patients with acute lymphocytic leukemia.
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CAR T-Cell Expansion Indicative of Response in B-cell LymphomaResearch presented at the EBMT meeting suggests cell expansion may be a good biomarker of both response and outcomes.
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KTE-X19 Demonstrates Comparable Pharmacologic, Clinical Outcomes to Approved Therapies in MCLThe pharmacodynamic profile of KTE-X19, an autologous anti-CD19 CAR T-cell therapy, was associated with efficacy and treatment-related neurological events among patients with relapsed/refractory mantle cell lymphoma treated within the ZUMA-2 trial.
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Early Research Signals Potential for CAR T-Cell Therapy in EGFRvIII-Positive GBMA pilot study of the efficacy of CAR T-cell therapy in patients with EGFRvIII-positive glioblastoma multiforme (GBM) has generated encouraging findings.
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Dr. Brudno on Allogeneic T Cells Expressing an Anti-CD19 CAR in B-Cell MalignanciesJennifer N. Brudno, MD, medical oncology fellow, National Cancer Institute, discusses a study examining allogeneic T cells expressing an anti-CD19 chimeric antigen receptor (CAR), which was found to cause remissions of B-cell malignancies after allogeneic hematopoietic stem cell transplantation without causing graft-versus-host disease.
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Using CAR T Therapy in R/R Multiple MyelomaNina Shah, MD, and other experts discuss the role of CAR T-cell therapy in relapsed/refractory multiple myeloma.
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Dr. Anwer on the Efficacy of CAR T-Cell Therapy in Multiple MyelomaFaiz Anwer, MD, discusses the efficacy of CAR T-cell therapy in multiple myeloma.
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Tumor-Treating Field Therapy Looks Beyond Brain CancerTumor-treating field therapy, which uses low-intensity electrical fields to disrupt cancer cell division and promote cell death, has gained a frontline approval in glioblastoma. Several pivotal clinical trials have been launched to determine whether the technology can help patients with other solid tumors.
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How Durable Are CAR T-Cell Therapies?The use of chimeric antigen receptor (CAR) T-cell therapies for the treatment of hematologic malignancies is still in its early stages, but when the FDA approved tisagenlecleucel and axicabtagene ciloleucel in 2017, this gave hope to oncologists and patients with some types of leukemia and lymphoma who have exhausted all other options.
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Starving Tumors of Important Amino Acid May Extend Survival in Pancreatic CancerInvestigators are evaluating whether eryaspase (Graspa), an L-asparaginase-based therapy that triggers tumor cell death, can extend survival for patients with pancreatic cancer.
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Novel T-Cell Therapies Make Inroads Into Solid TumorsAlthough CAR T-cell therapies have proved successful in certain hematologic malignancies, efforts to employ similar strategies in solid tumors have been challenging. Investigators are working on different forms of adoptive cell therapy in solid tumors and early signs are promising.
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CD19 CAR T-Cell Therapy Shows Efficacy in Real-World SettingInvestigators at Montefiore showed that axicabtagene-ciloleucel can be used successfully in ethnically diverse patients with high-risk, relapsed/refractory diffuse large B-cell lymphoma at an inner-city hospital.
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Chimeric Antigen Receptor (CAR) T-Cell Immunotherapy for Leukemia and BeyondChimeric antigen receptor T-cell therapy is an immunotherapy in which the patient's own T cells are isolated in the laboratory, redirected with a synthetic receptor to recognize a particular antigen or protein, and reinfused into the patient.
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Marcela Maus, MD, PhD, on New Research on CAR T for Solid Tumors, GlioblastomaThe Associate Professor of Medicine at Harvard Medical School shared her outlook on the trajectory of CAR T-cell therapy for treating solid tumors.
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Preoperative Therapy for Early-Stage NSCLC: Opportunities and ChallengesThe treatment of early-stage non–small-cell lung cancer (NSCLC) has undergone a paradigm shift recently with the addition of systemic therapy to local therapy. The use of cisplatin-based chemotherapy following surgery is now a standard approach for patients with stage II–IIIA disease.
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Non-Small-Cell Lung Cancer Adjuvant Therapy: Translating Data Into RealitySurgery remains the initial treatment for patients with early-stage non-small-cell lung cancer (NSCLC). Additional therapy is necessary because of high rates of distant and local disease recurrence after surgical resection. Early trials of adjuvant chemotherapy and postoperative radiation were often plagued by small patient sample size, inadequate surgical staging, and ineffective or antiquated treatment. A 1995 meta-analysis found a nonsignificant reduction in risk of death for postoperative cisplatin-based chemotherapy. Since then, a new generation of randomized phase III trials have been conducted, some of which have reported a benefit for chemotherapy in the adjuvant setting. The role of postoperative radiation therapy remains to be defined. It may not be beneficial in early-stage NSCLC but still may have utility in stage IIIA disease. Improvement in survival outcomes from adjuvant treatment are likely to result from the evaluation of novel agents, identification of tumor markers predictive of disease relapse, and definition of factors that determine sensitivity to therapeutic agents. Some of the molecularly targeted agents such as the angiogenesis and epidermal growth factor receptor inhibitors are being incorporated into clinical trials. Preliminary results with gene-expression profiles and lung cancer proteomics have been promising. These techniques may be used to create prediction models to identify patients at risk for disease relapse. Molecular markers such as ERCC1 may determine response to treatment. All of these innovations will hopefully increase cure rates for lung cancer patients by maximizing the efficacy of adjuvant therapy.
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Non-Small-Cell Lung Cancer Adjuvant Therapy: Translating Data Into RealitySurgery remains the initial treatment for patients with early-stage non-small-cell lung cancer (NSCLC). Additional therapy is necessary because of high rates of distant and local disease recurrence after surgical resection. Early trials of adjuvant chemotherapy and postoperative radiation were often plagued by small patient sample size, inadequate surgical staging, and ineffective or antiquated treatment. A 1995 meta-analysis found a nonsignificant reduction in risk of death for postoperative cisplatin-based chemotherapy. Since then, a new generation of randomized phase III trials have been conducted, some of which have reported a benefit for chemotherapy in the adjuvant setting. The role of postoperative radiation therapy remains to be defined. It may not be beneficial in early-stage NSCLC but still may have utility in stage IIIA disease. Improvement in survival outcomes from adjuvant treatment are likely to result from the evaluation of novel agents, identification of tumor markers predictive of disease relapse, and definition of factors that determine sensitivity to therapeutic agents. Some of the molecularly targeted agents such as the angiogenesis and epidermal growth factor receptor inhibitors are being incorporated into clinical trials. Preliminary results with gene-expression profiles and lung cancer proteomics have been promising. These techniques may be used to create prediction models to identify patients at risk for disease relapse. Molecular markers such as ERCC1 may determine response to treatment. All of these innovations will hopefully increase cure rates for lung cancer patients by maximizing the efficacy of adjuvant therapy.
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Adjuvant Endocrine Therapy for Breast Cancer: Longer Therapy and the Need for Personalized Treatment-Should We Treat Beyond the Data?In the future, we also need to improve our ability to personalize the duration of endocrine therapy, with a goal of optimizing patient selection for extended therapy. Hopefully, clinical-pathologic indices and predictive biomarkers similar to the Oncotype DX 12-gene recurrence score or the PAM50 risk of recurrence score for adjuvant chemotherapy will soon emerge to guide adjuvant endocrine therapy.
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p53 Tumor Suppressor Gene Therapy for CancerGene therapy has the potential to provide cancer treatments based on novel mechanisms of action with potentially low toxicities. This therapy may provide more effective control of locoregional recurrence in diseases like non–small-cell lung cancer (NSCLC) as well as systemic control of micrometastases. Despite current limitations, retroviral and adenoviral vectors can, in certain circumstances, provide an effective means of delivering therapeutic genes to tumor cells. Although multiple genes are involved in carcinogenesis, mutations of the p53 gene are the most frequent abnormality identified in human tumors. Preclinical studies both in vitro and in vivo have shown that restoring p53 function can induce apoptosis in cancer cells. High levels of p53 expression and DNA-damaging agents like cisplatin (Platinol) and ionizing radiation work synergistically to induce apoptosis in cancer cells. Phase I clinical trials now show that p53 gene replacement therapy using both retroviral and adenoviral vectors is feasible and safe. In addition, p53 gene replacement therapy induces tumor regression in patients with advanced NSCLC and in those with recurrent head and neck cancer. This article describes various gene therapy strategies under investigation, reviews preclinical data that provide a rationale for the gene replacement approach, and discusses the clinical trial data available to date. [ ONCOLOGY 13(Suppl 5):148-154, 1999]
Latest:
p53 Tumor Suppressor Gene Therapy for CancerGene therapy has the potential to provide cancer treatments based on novel mechanisms of action with potentially low toxicities. This therapy may provide more effective control of locoregional recurrence in diseases like non–small-cell lung cancer (NSCLC) as well as systemic control of micrometastases. Despite current limitations, retroviral and adenoviral vectors can, in certain circumstances, provide an effective means of delivering therapeutic genes to tumor cells. Although multiple genes are involved in carcinogenesis, mutations of the p53 gene are the most frequent abnormality identified in human tumors. Preclinical studies both in vitro and in vivo have shown that restoring p53 function can induce apoptosis in cancer cells. High levels of p53 expression and DNA-damaging agents like cisplatin (Platinol) and ionizing radiation work synergistically to induce apoptosis in cancer cells. Phase I clinical trials now show that p53 gene replacement therapy using both retroviral and adenoviral vectors is feasible and safe. In addition, p53 gene replacement therapy induces tumor regression in patients with advanced NSCLC and in those with recurrent head and neck cancer. This article describes various gene therapy strategies under investigation, reviews preclinical data that provide a rationale for the gene replacement approach, and discusses the clinical trial data available to date. [ ONCOLOGY 13(Suppl 5):148-154, 1999]
