IMMUNOTHERAPY

Bianca D. Santomasso, MD, PhD, discusses the challenges that exist for the treatment of patients with diffuse large B-cell lymphoma with CAR T-cell therapy.

Data from the&nbsp;phase Ib/II CARTITUDE-1 trial that were presented at the 2019 ASH Annual Meeting demonstrated the anti-BCMA CAR T-cell therapy JNJ-4528 achieved a 100% overall response rate with responses in 29 patients with heavily pretreated relapsed/refractory multiple myeloma.<br /> &nbsp;

An Investigational New Drug application for chimeric antigen receptor-T cell agent, ICTCAR014, has been cleared by the FDA for treatment of patients with relapsed/refractory non-Hodgkin lymphoma, including those with PD-L1-positive tumors, according to a press release from Innovative Cellular Therapeutics.

It is clear that cancer immunotherapy has progressed dramatically over the past 10 years, with over 20 FDA approvals for immune checkpoint receptor inhibitors targeting PD-1 and CTLA-4. However, we are still awaiting the next major advance in these inhibitory receptor targets that yields clinical benefit. In the meantime, additional advances have appeared.

Approximately 20% of cancers worldwide are linked to an infectious agent. Currently, there are seven known oncogenic viruses, which include Epstein-Barr virus, hepatitis virus B and C, human papillomavirus, human T cell lymphoma virus 1, Kaposi sarcoma virus and Merkel cell polyomavirus. Among these agents, HBV, HCV and HPV each contribute to ap- proximately 5% of all cancer cases.

Sarah Murawski, MPAS, discusses how telemedicine can impact the use of chimeric antigen receptor T-cell therapy in patients with cancer at the Association of Community Cancer Centers National Oncology Conference.

In an interview with&nbsp;Targeted Oncology during the 2019 Kidney Cancer Research Summit, Wayne A. Marasco, MD, PhD, discussed the intricacy of engineering CAR T cells and the early data he has observed with the approach in RCC.

In an interview with Targeted Oncology, Partow Kebriaei, MD, discussed the role of transplantation in patients with ALL following treatment with targeted cellular therapies, such as CAR T-cell therapy. She highlights the patient population that receives the most benefit from the use of CAR T-cell therapy and when transplant should be considered for these patients.

Over the last decade, immunotherapeutic options have led to impressive clinical responses in patients with various cancer types and this has increased expectations for successful treatment of the disease. Despite immunotherapy results leading to clinical trials in melanoma, renal cell carcinoma and non&ndash;small cell lung cancer, the percentage of patients who respond to immunotherapy remains low; this highlights the need to identify the patient population that will best respond to these approaches.

Building upon the initial successes of anti&ndash;PD-1 and anti&ndash;CTLA-4 therapies has been a major focus of drug development over the past several years&mdash;basically, in search of other agents that could generate &ldquo;immune-synergy.&rdquo; What the term means and implies is critically important: It refers to drugs that work better together than alone (or in sequence) through their individual mechanisms of action to enhance the host immune-response to cancer.

In an interview with Targeted Oncology, Bianca D. Santomasso, MD, PhD,&nbsp;discussed the challenges with treating patients who develop neurotoxicity following treatment with new CAR T cells following her talk at the 2019 SOHO Annual Meeting. She also highlighted how the CAR T cells are changing the treatment landscape for patients with lymphomas.

This year&rsquo;s Hot Topic Symposium during Society for Immunotherapy of Cancer&rsquo;s 34th Annual Meeting, co-chaired by Jennifer A. Ligibel, MD, and Jennifer Mcquade, MD, MS, MA, focused on modifiable factors that can affect tumor response to treatment.

Although immune checkpoint inhibitor therapy has represented a paradigm shift in the treatment of multiple types of cancer, many patients&rsquo; cancers do not respond at all to these therapies or develop resistance after an initial period of response, according to Julie R. Brahmer, MD.&nbsp;

The advent of immunotherapy has delivered unprecedented and durable anti-tumor responses as well as long-lasting survival benefits in some patients. Yet many clinicians may not be familiar with managing the unique toxicities that accompany these emerging cancer treatments.

The combination of bemcentinib, a first in class selective AXL inhibitor, and pembrolizumab is well-tolerated in patients with composite AXL-positive non&ndash;small cell lung cancer, according to updated data presented at Society for Immunotherapy of Cancer&rsquo;s 34th Annual Meeting.

The use of CMP-001, an intratumoral toll-like receptor 9 agonist, is capable of triggering durable responses when used in combination with pembrolizumab for patients with PD-1 resistant metastatic melanoma according to results from a phase Ib study presented at the Society for Immunotherapy of Cancer&rsquo;s 34th Annual Meeting.

The anti&ndash;CD27 agonist, MK-5890, demonstrated acceptable safety findings when administered as monotherapy and in combination with pembrolizumab in numerous solid tumors, according to findings of an open-label phase I trial presented by Ronnie Shapira-Frommer, MD, head of the Onco-Gynecological Cancer Unit at The Ella Lemelbaum Institute for Immuno-Oncology, Ramat Gan, Israel, during the Society for Immunotherapy of Cancer&rsquo;s 34^th Annual Meeting.

Immunotherapy combination regimens have revolutionized the first-line treatment paradigm for patients with clear cell renal cell carcinoma, explained Robert J. Motzer, MD, at the <em>37th Annual</em> CFS.

There are at least two dozen different B-cell maturation antigen-directed therapies being explored in clinical trials, Sham Mailankody, MBBS, told attendees at the 37 Annual CFS.&nbsp;Mailankody, an assistant attending physician at Memorial Sloan Kettering Cancer Center in New York, New York, highlighted the most promising anti-BCMA agents across several modalities, including CAR T-cell therapy, bispecific antibodies, and antibody-drug conjugates.

David Maloney, MD, PhD, medical director, Cellular Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Research Center, discusses the results of the ZUMA trial and how chimeric antigen receptor CAR T-cell therapy is changing the treatment landscape for non-Hodgkin lymphoma.

Non-Hodgkin Lymphoma

In solid tumors, targeted therapies are scarce for patients with mutations like KRAS or fusions like NRG1. Two clinical trials are investigating novel agents targeting these alterations to improve outcomes in patients with these particular genetic drivers of disease. The research was recently presented at the 2019 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics.

The results of multiple studies suggest that bacteria may influence both cancer growth and the immune system, with certain species linked to improved immune surveillance of cancer. Some bacteria interact with the host&rsquo;s immune system through paracrine factors to shape the immune system&rsquo;s response to cancer.

Emerging from the recent 2019 World Conference on Lung Cancer&nbsp;are several notable developments, Robert L. Ferris, MD, PhD, wrote in this issue of&nbsp;<em>Targeted Therapies in Oncology.&nbsp;</em>

<br /> In the future, we&rsquo;re going to do combination therapies. They will be used in a subset of patients better defined by profiling,&rdquo; Kenneth C. Anderson, MD, told an audience at the Charlotte Plasma Cell Disorder Congress in North Carolina.

Marcelo C. Pasquini, MD, discusses the rationale for analyzing real-world data for the use of tisagenlecleucel, a chimeric antigen receptor T-cell therapy, as a treatment for patients with acute lymphoblastic leukemia and diffuse large B-cell lymphoma. This CD19 CAR T cell was approved 2 years ago for use in both ALL and DLBCL.

Patients with early triple-negative breast cancer receiving neoadjuvant treatment with the combination of pembrolizumab and chemotherapy showed extended pathological complete response rates by 13.6 percentage points compared with chemotherapy alone in the phase III KEYNOTE-522 study.

Certain patients with cancer who are treated using immune checkpoint inhibitors may develop a form of insulin-dependent diabetes that is associated with immune-related adverse events resulting from therapy, according to research published in <em>The Lancet Diabetes &amp; Endocrinology</em>.

Now in it 24th year, the annual International Congress on Hematologic Malignancies: Focus on Leukemias, Lymphomas, and Myeloma, hosted by Physicians&rsquo; Education Resource, LLC, continues to bring significant advances in hematology to the forefront.

To improve the efficacy of chimeric antigen receptor T-cell therapies, Nirali N. Shah, MD, MHSc, suggested including new constructs that target more than 1 antigen in patients with acute lymphoblastic leukemia, during a presentation at the 2019 SOHO Annual Meeting.<br /> &nbsp;