Current Oncology

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Open AccessEditor’s ChoiceReview

Immunotherapy in Hematologic Malignancies

by R.R. Kansara and C. Speziali

Curr. Oncol. 2020, 27(s2), 124-131; https://doi.org/10.3747/co.27.5117 - 01 Apr 2020

Cited by 18 | Viewed by 1576

The management of hematologic malignancies has traditionally relied on chemotherapy regimens, many of which are still in use today. However, with advancements in the knowledge of tumour pathophysiology, therapies are continually evolving. Monoclonal antibodies against specific targets on tumour cells are now widely [...] Read more.

The management of hematologic malignancies has traditionally relied on chemotherapy regimens, many of which are still in use today. However, with advancements in the knowledge of tumour pathophysiology, therapies are continually evolving. Monoclonal antibodies against specific targets on tumour cells are now widely used to treat hematologic malignancies, either in combination with chemotherapy or as single agents. Rituximab, a monoclonal antibody against the CD20 antigen, is a good example of successful monoclonal antibody therapy that has improved outcomes for patients with B cell non-Hodgkin lymphomas. Monoclonal antibodies are now being used against the immune checkpoints that function to inhibit T cell activation and subsequent tumour eradication by those cytotoxic T cells. Such therapies enhance T cell–mediated tumour eradication and are widely successful in treating patients with solid tumours such as malignant melanoma. Now, they are slowly finding their place in the management of hematologic neoplasms. Even though, currently, immune checkpoint inhibitors are used for relapsed or refractory hematologic neoplasms, trials are ongoing to evaluate their role in frontline treatment. Our review focuses on the current use of immunotherapies in various hematologic malignancies. Full article

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Open AccessReview

Chimeric Antigen Receptor T Cell Therapy Comes to Clinical Practice

by D.A. Wall and J. Krueger

Curr. Oncol. 2020, 27(s2), 115-123; https://doi.org/10.3747/co.27.5283 - 01 Apr 2020

Cited by 24 | Viewed by 1697

Abstract

Adoptive cellular therapy with chimeric antigen receptor T cells (car-ts) has recently received approval from Health Canada and the U.S. Food and Drug Administration after remarkable and durable remissions were seen in children with recurrent or refractory leukemia and adults with [...] Read more.

Adoptive cellular therapy with chimeric antigen receptor T cells (car-ts) has recently received approval from Health Canada and the U.S. Food and Drug Administration after remarkable and durable remissions were seen in children with recurrent or refractory leukemia and adults with non-Hodgkin lymphoma—responses that were so impressive that a shift in the paradigm of care has now occurred for children with acute lymphoblastic leukemia. The concept behind car-t immunotherapy is that modification of a patient’s own T cells to facilitate their localization to the cancer cell, with subsequent activation of the T cell effector mechanism and proliferation, will result in targeted killing of cancer cells. The car-ts are a novel drug in that the starting material for the manufacture of the car-t product comes from the patient, whose viable T cells are then genetically modified. Thus, collaboration is needed between the pharmaceutical companies, which must meet good manufacturing standards for each patient’s unique product, and the treating sites. For regulators and health authorities, this new class of drugs requires new paradigms for assessment and approval. Treatments with car-ts require that institutions address unique logistics requirements and management of novel toxicities. The Hospital for Sick Children has had early experience with both the licensing of clinical trials and the introduction of the first commercial product. Here, we provide an overview of basic concepts and treatment, with caveats drawn from what we have learned thus far in bringing this new therapy to the clinical front line. Full article

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Open AccessReview

Biomarkers of Immune Checkpoint Inhibitor Efficacy in Cancer

by D.E. Meyers and S. Banerji

Curr. Oncol. 2020, 27(s2), 106-114; https://doi.org/10.3747/co.27.5549 - 01 Apr 2020

Cited by 18 | Viewed by 1315

Abstract

Immune checkpoint inhibitor–based therapies that target ctla-4, PD-1, or the PD-1 ligand PD-L1 have received approval in Canada and many parts of the world for the treatment of melanoma, renal cell cancer, urothelial cancer, classical Hodgkin lymphoma, and non-small-cell lung cancer. However [...] Read more.

Immune checkpoint inhibitor–based therapies that target ctla-4, PD-1, or the PD-1 ligand PD-L1 have received approval in Canada and many parts of the world for the treatment of melanoma, renal cell cancer, urothelial cancer, classical Hodgkin lymphoma, and non-small-cell lung cancer. However only a small proportion of patients derive long-term clinical benefit. Here, we describe the biomarkers associated with the complex relationship between tumour-related immune stimulus, T cell–mediated immune response, and immune modulation of the microenvironment that can help to predict improved patient outcomes. Full article

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Open AccessReview

Targeting T Cell Activation in Immuno-Oncology

by S.D. Saibil and P.S. Ohashi

Curr. Oncol. 2020, 27(s2), 98-105; https://doi.org/10.3747/co.27.5285 - 01 Apr 2020

Cited by 22 | Viewed by 1765

Abstract

The years since 2009 have seen tremendous progress in unlocking the curative potential of the immune system for the treatment of cancer. Much of that revolution in immuno-oncology has been fueled by the clinical success of immune checkpoint inhibitors, particularly those targeting the [...] Read more.

The years since 2009 have seen tremendous progress in unlocking the curative potential of the immune system for the treatment of cancer. Much of that revolution in immuno-oncology has been fueled by the clinical success of immune checkpoint inhibitors, particularly those targeting the PD-1 axis. Unfortunately, many patients still fail to benefit from checkpoint blockade or other immunotherapies. An inability to fully activate antitumour T cells contributes in part to the failure of those therapies. Here, we review the basic biology of T cell activation, with particular emphasis on the essential role of the dendritic cell and the innate immune system in T cell activation. The current understanding of the multiple factors that govern T cell activation and how they impinge on tumour immunotherapy are also discussed. Lastly, treatment strategies to potentially overcome barriers to T cell activation and to enhance the efficacy of immunotherapy are addressed. Full article

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Open AccessEditor’s ChoiceReview

A Review of Cancer Immunotherapy: From the Past, to the Present, to the Future

by K. Esfahani, L. Roudaia, N. Buhlaiga, S.V. Del Rincon, N. Papneja and W.H. Miller

Curr. Oncol. 2020, 27(s2), 87-97; https://doi.org/10.3747/co.27.5223 - 01 Apr 2020

Cited by 545 | Viewed by 22027

Abstract

Compared with previous standards of care (including chemotherapy, radiotherapy, and surgery), cancer immunotherapy has brought significant improvements for patients in terms of survival and quality of life. Immunotherapy has now firmly established itself as a novel pillar of cancer care, from the metastatic [...] Read more.

Compared with previous standards of care (including chemotherapy, radiotherapy, and surgery), cancer immunotherapy has brought significant improvements for patients in terms of survival and quality of life. Immunotherapy has now firmly established itself as a novel pillar of cancer care, from the metastatic stage to the adjuvant and neoadjuvant settings in numerous cancer types. In this review article, we highlight how the history of cancer immunotherapy paved the way for discoveries that are now part of the standard of care. We also highlight the current pitfalls and limitations of cancer checkpoint immunotherapy and how novel research in the fields of personalized cancer vaccines, autoimmunity, the microbiome, the tumour microenvironment, and metabolomics is aiming to solve those challenges. Full article

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Open AccessReview

Immuno-Oncology—The New Paradigm of Lung Cancer Treatment

by D.E. Dawe, C.H. Harlos and R.A. Juergens

Curr. Oncol. 2020, 27(s2), 78-86; https://doi.org/10.3747/co.27.5183 - 01 Apr 2020

Cited by 20 | Viewed by 1753

Abstract

Systemic therapy is an essential part of treatment for all patients with small-cell lung cancer (sclc) and for most patients with non-small-cell lung cancer (nsclc). Standards of care have evolved dramatically since 2009, especially in the setting of incurable [...] Read more.

Systemic therapy is an essential part of treatment for all patients with small-cell lung cancer (sclc) and for most patients with non-small-cell lung cancer (nsclc). Standards of care have evolved dramatically since 2009, especially in the setting of incurable or advanced nsclc. Part of that evolution has been the incorporation of immuno-oncology drugs, especially immune checkpoint inhibitors (icis) into multiple therapeutic scenarios. In the present review, we discuss the role of the immune system in lung cancer and the previous failures of immunotherapy for patients with lung cancer. We then provide an overview of the existing evidence for the use of icis in patients with advanced nsclc that is either treatment-naïve or pretreated, for consolidative treatment after chemoradiotherapy in stage iii nsclc, and for palliative therapy in patients with sclc. Finally, we discuss duration of treatment, special populations, and the future of immuno-oncology for patients with lung cancer. Overall, we provide an evidence-based snapshot of immuno-oncology agents in the treatment of lung cancer up to early 2019. Full article

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Open AccessEditor’s ChoiceReview

Immune Checkpoint Inhibitors in Genitourinary Malignancies

by M. Thana and L. Wood

Curr. Oncol. 2020, 27(s2), 69-77; https://doi.org/10.3747/co.27.5121 - 01 Apr 2020

Cited by 10 | Viewed by 1273

Abstract

Although immune-mediated therapies have been used in genitourinary (gu) malignancies for decades, recent advances with monoclonal antibody checkpoint inhibitors (cpis) have led to a number of promising treatment options. In renal cell carcinoma (rcc), cpis have [...] Read more.

Although immune-mediated therapies have been used in genitourinary (gu) malignancies for decades, recent advances with monoclonal antibody checkpoint inhibitors (cpis) have led to a number of promising treatment options. In renal cell carcinoma (rcc), cpis have been shown to have benefit over conventional therapies in a number of settings, and they are the standard of care for many patients with metastatic disease. Based on recent data, combinations of cpis and antiangiogenic therapies are likely to become a new standard approach in rcc. In urothelial carcinoma, cpis have been shown to have a role in the second-line treatment of metastatic disease, and a number of clinical trials are actively investigating cpis for other indications. In other gu malignancies, such as prostate cancer, results to date have been less promising. Immunotherapies continue to be an area of active study for all gu disease sites, with several clinical trials ongoing. In this review, we summarize the current evidence for cpi use in rcc, urothelial carcinoma, prostate cancer, testicular germ-cell tumours, and penile carcinoma. Ongoing clinical trials of interest are highlighted, as are the challenges that clinicians and patients will potentially face as immune cpis become a prominent feature in the treatment of gu cancers. Full article

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Open AccessReview

Cautious Optimism—The Current Role of Immunotherapy in Gastrointestinal Cancers

by S. Mendis and S. Gill

Curr. Oncol. 2020, 27(s2), 59-68; https://doi.org/10.3747/co.27.5095 - 01 Apr 2020

Cited by 4 | Viewed by 1264

Abstract

Immunotherapy has been described as the “fourth pillar” of oncology treatment, in conjunction with surgery, chemotherapy, and radiotherapy. However, the role of immunotherapy in gastrointestinal tumours is still evolving. Data for checkpoint inhibition in esophagogastric, hepatocellular, colorectal, and anal squamous cell carcinomas are [...] Read more.

Immunotherapy has been described as the “fourth pillar” of oncology treatment, in conjunction with surgery, chemotherapy, and radiotherapy. However, the role of immunotherapy in gastrointestinal tumours is still evolving. Data for checkpoint inhibition in esophagogastric, hepatocellular, colorectal, and anal squamous cell carcinomas are expanding. In phase iii trials in the second-line setting, PD-1 inhibitors have demonstrated positive results for the subset of esophageal cancers that are positive for PD-L1 at a combined positive score of 10 or more. Based on results of phase ii trials, PD-1 inhibitors were approved in North America for use in PD-L1–positive chemorefractory gastric cancers, in hepatocellular carcinoma after sorafenib exposure, and in treatment-refractory deficient mismatch repair (dmmr) or high microsatellite instability (msi-h) tumours, regardless of tissue site. Combination use of PD-1 and ctla-4 inhibitors has been approved by the U.S. Food and Drug Administration for chemorefractory dmmr or msi-h colorectal cancer. Responses to checkpoint inhibition are durable, particularly in the dmmr or msi-h colorectal cancer cohort. As trials of combination immunotherapy, immunotherapy in combination with other systemic therapies, and immunotherapy in combination with other treatment modalities move forward in multiple tumour sites, cautious optimism is called for. The treatment landscape is continually changing, and expanded indications are likely to be just around the corner. Full article

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Open AccessReview

Use of Immuno-Oncology in Melanoma

by M.G. Smylie

Curr. Oncol. 2020, 27(s2), 51-58; https://doi.org/10.3747/co.27.5135 - 01 Apr 2020

Cited by 12 | Viewed by 1284

Abstract

Treatment options for patients with metastatic melanoma have expanded rapidly since the approval of ipilimumab by the U.S. Food and Drug Administration in 2011. Cytokines such as interferon and interleukin-2 were approved in 1995 and 1998 respectively. However, the effect on survival was [...] Read more.

Treatment options for patients with metastatic melanoma have expanded rapidly since the approval of ipilimumab by the U.S. Food and Drug Administration in 2011. Cytokines such as interferon and interleukin-2 were approved in 1995 and 1998 respectively. However, the effect on survival was marginal, and the toxicity, substantial. Multiple vaccine studies likewise failed to show improvements in survival. The “Holy Grail” came with the discovery of immune checkpoints, and the first metastatic melanoma trial to show an improvement in overall survival involved the use of an immune checkpoint inhibitor against ctla-4: ipilimumab. Since then, the field of immuno-oncology has exploded, with approvals for PD-1 inhibitors and discovery, in clinical trials, of several novel checkpoints such as tim-3, lag-3, and others. In fact more than 950 novel immunotherapy drugs are currently being trialled. Recently, combinations of ctla-4 and PD-1 inhibitors have been associated with 1-year survival rates exceeding 80% and 4-year survival rates greater than 50%. In no tumour has as much progress been made in the last 5 years as in melanoma, and the efforts to unravel and exploit mechanisms used by the tumour to avoid immune detection are just beginning. Full article

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Open AccessReview

Diagnosis, Monitoring, and Management of Adverse Events From Immune Checkpoint Inhibitor Therapy

by O.F. Khan and J. Monzon

Curr. Oncol. 2020, 27(s2), 43-50; https://doi.org/10.3747/co.27.5111 - 01 Apr 2020

Cited by 13 | Viewed by 1008

Abstract

Immune checkpoint inhibitor therapy (icit) is now a standard of care for a variety of cancers in both the metastatic and adjuvant settings. As a result, an understanding of the timing, epidemiology, monitoring, diagnosis, and management of immune-related adverse events (ir [...] Read more.

Immune checkpoint inhibitor therapy (icit) is now a standard of care for a variety of cancers in both the metastatic and adjuvant settings. As a result, an understanding of the timing, epidemiology, monitoring, diagnosis, and management of immune-related adverse events (iraes) associated with icit is imperative. This article reviews specific iraes by organ system, consolidating recommendations from multiple guidelines and incorporating data from case reports to highlight additional evolving therapeutic options for patients. Managing iraes requires early recognition, early intervention, and education of the patients and the multidisciplinary health care team alike. Given the durable responses observed with icit, and the irreversible nature of some of the iraes, further research into management of the sequelae of icit is required. Full article

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Open AccessEditorial

A New Hope

by R. Wong

Curr. Oncol. 2020, 27(s2), 41-42; https://doi.org/10.3747/co.27.6035 - 01 Apr 2020

Viewed by 436

Abstract

Immuno-oncology uses the body’s inherent immune system to combat malignancy. […]
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Curr. Oncol., Volume 27, Issue s2 (April 2020) – 11 articles

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