Oncology Central

One hundred and thirty seven conditions, one big problem: exploring new horizons in hematologic oncology

0
As you may be aware, September is Blood Cancer Awareness Month – a month in which many charities and research bodies work to increase public awareness, and highlight the importance and need for ongoing research towards developing new therapies. One excellent example is the new campaign spearheaded by the UK charity Bloodwise, as they work to raise blood cancer awareness, specifically highlighting how there are 137 various manifestations of hematologic malignancies and related disorders [1].

That is 137 different conditions classified under this one area of oncology – and every 14 minutes in the UK alone an individual is diagnosed with one of these diseases [2]. Statistics also demonstrate that overall leukemia, lymphoma and myeloma, taken together, represent the fifth most commonly occurring cancers and the second leading cause of cancer death. These stark facts do well to portray the breadth of the challenge of both raising public understanding and of developing therapies to overcome these conditions.

Speaking to Oncology Central regarding the extent of the health issue at hand and their motivation behind the campaign, Diana Jupp, Director of Patient Experience at Bloodwise, commented: “We’ve launched our campaign in response to a crisis in awareness of blood cancers. While 38,000 people are diagnosed with a blood cancer each year in the UK, very few people are familiar with the term ’blood cancer’.”

“Patients have told us that a lack of awareness has a significant impact throughout their patient journey – from confusion and uncertainty at diagnosis to being unaware of the organizations that provide the support and care they need. This lack of awareness cannot be tackled overnight, and this campaign, along with its 3,000 billboards, is the first step to addressing the problem.”

Bloodwise champion the belief that blood cancer can be beaten through continued investment in world-class research, thought leadership and patient support, while also working to inform those across the political spectrum of the policy priorities they believe will help beat blood cancers [3].

In support of Blood Cancer Awareness month, this week on Oncology Central we are also turning our attention to blood cancer and the ongoing global research being carried out, often funded by organizations such as Bloodwise and Cancer Research UK, with one goal in mind – developing cures for this huge array of diseases. It can certainly be argued that promising research, new targeted therapies and advances in chemotherapy have contributed to the significant progress made within the field of hematologic oncology in recent years – yet this momentum must continue.

During this focus on hematologic oncology, we are exploring some of the latest research and clinical studies being carried out in these diseases. We have taken the star of the year thus far – cancer immunotherapy – and selected some top peer-reviewed content discussing the current applications and future prospects of this exciting treatment modality in hematologic malignancies. Find out what experts from The Ohio State University Comprehensive Cancer Center (OH, USA) and University of Rochester Medical Center (NY, USA) have to say on this topic in our hematologic section.

As we well know, hematologic cancers are an active area of cancer research, both at the benchside and in the clinic – a simple search of the word ‘leukemia’ on clinicaltrials.gov returns in excess of 5000 trial results. Alongside the excellent journal content detailed above, we’ve also been delving into some of the most recent hematologic headlines this week, sizing up what new avenues researchers and clinicians are investigating to both learn more about these diseases and to develop better therapies.

Saving approximately 1000 lives a year with new training course

Enabling earlier diagnosis of cancer is almost always flagged as a key unmet need when it comes to improving survival rates, as when caught earlier malignancies are generally more treatable. As the symptoms of blood cancers can be less specific and thus linked with a whole host of less serious conditions, approximately a third of all cases are diagnosed via the emergency admissions route. For example in myeloma, the 1-year survival rate for individuals diagnosed after a referral from their doctor is 83.9%, compared with 53.1% if diagnosis is delayed.

The Royal College of General Practitioners in collaboration with the charity Leukaemia CARE have recently developed a free online training course for general practitioners, designed to raise awareness of blood cancers with an aim of improving early diagnosis [4]. This represents the first tool of its kind for blood cancer, combining information on identifying symptoms and case studies.

“Blood cancer is very difficult to diagnose in primary care – an average GP might only see one new case of blood cancer a year, if any – but it has the third biggest cancer death rate in the UK, so it is essential that healthcare professionals are supported to identify the signs and symptoms of blood cancer so that they can deliver as timely a diagnosis as possible,” commented Ishani Patel, Clinical Lead for Early Diagnosis of Cancer and Quality Improvement at the Royal College of General Practitioners.

“We hope that this new online training course will become an invaluable resource for GPs and their teams and support them in providing excellent care to patients with blood cancer through their diagnosis and beyond,” she concluded.

Editing enzyme’s erroneous effects explored

Turning focus to the benchside for a moment, an interesting study from the Perelman School of Medicine at the University of Pennsylvania (PA, USA) has uncovered another potential reason why blood cancers develop [5]. The study, which appeared recently in Cell Reports, concluded that off-target effects of V(D)J recombinase – the enzyme that is responsible for generating surface receptors on immune cells – can result in the development of cancer in animal models.

Active during the early stages of immune cell maturation, this enzyme is key to cutting and pasting segments of DNA. Breaks in the DNA created by V(D)J recombinase are ordinarily repaired with great accuracy by cell machinery – prompted by the RAG2 protein subunit of the recombinase complex. However, the activation of appropriate DNA repair mechanisms can be interrupted if the C terminus of the RAG2 protein subunit is removed, resulting in genomic instability in developing immune cells and off-target recombination errors associated with V(D)J. The study found that truncation of RAG2 promoted development of an aggressive form of lymphoma in mice without functional p53 [6].

Chronic lymphocytic leukemia therapy gets personal

Some interesting results have recently emerged from a pilot clinical trial investigating a personalized cell therapy in chronic lymphocytic leukemia, termed CTL019. Eight of the 14 patients involved in the trial, also carried out at the University of Pennsylvania, are reported to have responded to the treatment, with some complete remissions lasting in excess of 4.5 years [7].

Appearing recently in Science Translational Medicine, the new study details the data from the completed trial of this immune cell therapy, which began in 2010. CTL019 is developed from a patient’s own T cells, which are isolated and reprogrammed to target cancer cells using an antibody-like protein known as a chimeric antigen receptor, designed to target CD19 on the surface of B cells.

For the whole study period, the overall response rate was 57%, with four patients achieving complete remission. Three of these individuals were alive at the time of this analysis with no evidence of leukemia at 28, 52, and 53 months after therapy. Furthermore, four patients achieved a partial response, six did not respond and one progressed following therapy. In those who did not respond, tests revealed that the modified T cells did not expand as robustly as in those who experienced remissions.

“The durability of the remissions we have observed in this study are remarkable and have given us great hope that personalized cell therapies are going to be important options for patients whose cancers are no longer treatable with standard approaches,” commented lead author David L Porter of Penn’s Abramson Cancer Center. “The patients in this study are pioneers, whose participation has given us a foundation of knowledge and experience on which to build this new approach to help more patients.”

Immunotherapy vs. drug-resistant multiple myeloma

Another recent study from investigators at Penn also demonstrated the potential efficacy of the CTL019 CAR-T immunotherapy in a patient with multiple myeloma. The individual in question had experienced disease progression on nine different cancer therapies, yet when treated with CTL019 experienced a complete remission [8].

The report is a follow-up to a presentation at the 2015 American Society of Clinical Oncology meeting, where data concerning the first five multiple myeloma patients treated with CTL019 and an infusion of their own stem cells were released. Reporting now on the overall progress of the trial, the Penn team suggest that of the ten patients who have received the therapy to date, six remain progression free.

“There was some skepticism about whether a CD19-directed therapy would work in this disease, since nearly all of these patients’ cancerous plasma cells do not express CD19,” explained the study’s senior author Edward Stadtmauer of Penn’s Abramson Cancer Center and Perelman School of Medicine. “Since there was data showing that the possible stem cells can be CD19-positive, our hypothesis was that we may be able to devise a therapy targeted at early precursors of those cells.”

Lastly, a recent study published in the New England Journal of Medicine has demonstrated the efficacy of the antibody immunotherapy daratumumab also in drug-resistant multiple myeloma [9].

In the first clinical trial of this therapy, clinicians at Dana-Farber Cancer Institute (NY, USA) and other organizations investigated CD38-targeting daratumumab in 72 patients all of whom had received at least two prior therapies and whose disease had relapsed and was no longer responding. Two different doses of the agent were investigated and of the 42 individuals who received a higher dosage, 36% experienced durable reponses, including two who had complete remissions. In this group, the median period of disease control was 5.6 months and two-thirds of those who benefited from the drug had no disease progression for at least 12 months.

“As a single-agent therapy, daratumumab showed significant promise against difficult-to-treat disease in our patients with advanced myeloma and who have few other therapeutic options,” remarked lead investigator Paul Richardson of Dana-Farber Cancer Institute. “Because it targets a key receptor and works through different mechanisms than other available agents, it clearly has merited comprehensive testing in larger clinical trials. Preliminary results from these studies have been very encouraging.”

These stories represent just a snapshot of the news and activity of researchers around the world, who continue to investigate new methods of treating these cancers. In the words of Bloodwise – do you believe the writing is on the wall for all these hematologic malignancies? Share your thoughts with us in the comment box below.

Sources:

  1. https://bloodwise.org.uk/
  2. https://bloodwise.org.uk/page/facts-and-information-about-blood-cancer
  3. https://bloodwise.org.uk/we-campaign?section=our%20policy%20priorities
  4. http://www.medicalnewstoday.com/releases/299049.php
  5. http://www.uphs.upenn.edu/news/News_Releases/2015/09/roth/
  6. http://www.cell.com/cell-reports/abstract/S2211-1247(15)00919-5?_returnURL=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2211124715009195%3Fshowall%3Dtrue
  7. http://www.uphs.upenn.edu/news/News_Releases/2015/09/june/
  8. http://www.uphs.upenn.edu/news/News_Releases/2015/09/garfall/
  9. http://www.dana-farber.org/Newsroom/News-Releases/Immunotherapy-agent-benefits-patients-with-drug-resistant-multiple-myeloma-in-first-human-trial.aspx
Share:

Leave A Comment