In June, at the European Haematology Association conference, members from acute leukemia patient advocate groups across the globe joined together to discuss the creation of an Acute Leukemia Advocates Network (ALAN).
ALAN has now been formally founded, hosted by the Leukemia Patients Advocates Foundation. ALAN aims to build capacity in the members of the network to deliver tailored services to acute leukemia patients and carers on the national level, while joining forces between organisations on the policy and research level across countries.
Non-profit patient organizations, with a sole or partial focus on acute leukemia, are eligible to apply for membership of ALAN.
Zack Pemberton-Whiteley commented: “The creation of ALAN is a positive step forward for acute leukemia patients. ALAN provides the opportunity to strengthen the work and the voice of advocates across the globe. Both patients and carers will benefit from the development of tailored information and support services for acute leukemia. Patient advocacy organisations, such as Leukaemia CARE, will also be better equipped to support patients and carers by learning best practices from one another.”
Here at the Acute Leukemia Advocates Network (ALAN), we recognise the importance of informing our work based on the patient and carer experience.
That’s why this September for Blood Cancer Awareness Month, ALAN is supporting Leukaemia Care’s Spot Leukaemia campaign. The campaign seeks to raise awareness of leukemia and the key symptoms to spot. The campaign was directed by Leukaemia Care’s patient experience survey that identified a number of issues in patient experience at diagnosis.
Leukaemia Care’s patient experience survey was one of the biggest done to date (including 500+ acute leukemia patients), which is significant for directing future work in a patient focussed and evidence based manner.
For example, the survey found that 44% of acute leukemia patients experienced symptoms for over a month before visiting their general practitioner (GP). This highlights an issue with the public recognising the signs and symptoms of leukemia, leading to a delay in diagnosis. The quickly progressing nature of acute leukemia means that a delay in diagnosis and treatment could significantly impact the patient’s outcome.
The U.S. Food and Drug Administration issued a historic action today making the first gene therapy available in the United States, ushering in a new approach to the treatment of cancer and other serious and life-threatening diseases.
The FDA approved Kymriah (tisagenlecleucel) for certain pediatric and young adult patients with a form of acute lymphoblastic leukemia (ALL).
“We’re entering a new frontier in medical innovation with the ability to reprogram a patient’s own cells to attack a deadly cancer,” said FDA Commissioner Scott Gottlieb, M.D. “New technologies such as gene and cell therapies hold out the potential to transform medicine and create an inflection point in our ability to treat and even cure many intractable illnesses. At the FDA, we’re committed to helping expedite the development and review of groundbreaking treatments that have the potential to be life-saving.”
Kymriah, a cell-based gene therapy, is approved in the United States for the treatment of patients up to 25 years of age with B-cell precursor ALL that is refractory or in second or later relapse.
Kymriah is a genetically-modified autologous T-cell immunotherapy. Each dose of Kymriah is a customized treatment created using an individual patient’s own T-cells, a type of white blood cell known as a lymphocyte. The patient’s T-cells are collected and sent to a manufacturing center where they are genetically modified to include a new gene that contains a specific protein (a chimeric antigen receptor or CAR) that directs the T-cells to target and kill leukemia cells that have a specific antigen (CD19) on the surface. Once the cells are modified, they are infused back into the patient to kill the cancer cells.
ALL is a cancer of the bone marrow and blood, in which the body makes abnormal lymphocytes. The disease progresses quickly and is the most common childhood cancer in the U.S. The National Cancer Institute estimates that approximately 3,100 patients aged 20 and younger are diagnosed with ALL each year. ALL can be of either T- or B-cell origin, with B-cell the most common. Kymriah is approved for use in pediatric and young adult patients with B-cell ALL and is intended for patients whose cancer has not responded to or has returned after initial treatment, which occurs in an estimated 15-20 percent of patients.
“Kymriah is a first-of-its-kind treatment approach that fills an important unmet need for children and young adults with this serious disease,” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research (CBER). “Not only does Kymriah provide these patients with a new treatment option where very limited options existed, but a treatment option that has shown promising remission and survival rates in clinical trials.”
The safety and efficacy of Kymriah were demonstrated in one multicenter clinical trial of 63 pediatric and young adult patients with relapsed or refractory B-cell precursor ALL. The overall remission rate within three months of treatment was 83 percent.
Treatment with Kymriah has the potential to cause severe side effects. It carries a boxed warning for cytokine release syndrome (CRS), which is a systemic response to the activation and proliferation of CAR T-cells causing high fever and flu-like symptoms, and for neurological events. Both CRS and neurological events can be life-threatening. Other severe side effects of Kymriah include serious infections, low blood pressure (hypotension), acute kidney injury, fever, and decreased oxygen (hypoxia). Most symptoms appear within one to 22 days following infusion of Kymriah. Since the CD19 antigen is also present on normal B-cells, and Kymriah will also destroy those normal B cells that produce antibodies, there may be an increased risk of infections for a prolonged period of time.
The FDA today also expanded the approval of Actemra (tocilizumab) to treat CAR T-cell-induced severe or life-threatening CRS in patients 2 years of age or older. In clinical trials in patients treated with CAR-T cells, 69 percent of patients had complete resolution of CRS within two weeks following one or two doses of Actemra.
Because of the risk of CRS and neurological events, Kymriah is being approved with a risk evaluation and mitigation strategy (REMS), which includes elements to assure safe use (ETASU). The FDA is requiring that hospitals and their associated clinics that dispense Kymriah be specially certified. As part of that certification, staff involved in the prescribing, dispensing, or administering of Kymriah are required to be trained to recognize and manage CRS and neurological events. Additionally, the certified health care settings are required to have protocols in place to ensure that Kymriah is only given to patients after verifying that tocilizumab is available for immediate administration. The REMS program specifies that patients be informed of the signs and symptoms of CRS and neurological toxicities following infusion – and of the importance of promptly returning to the treatment site if they develop fever or other adverse reactions after receiving treatment with Kymriah.
To further evaluate the long-term safety, Novartis is also required to conduct a post-marketing observational study involving patients treated with Kymriah.
The FDA granted Kymriah Priority Review and Breakthrough Therapy designations. The Kymriah application was reviewed using a coordinated, cross-agency approach. The clinical review was coordinated by the FDA’s Oncology Center of Excellence, while CBER conducted all other aspects of review and made the final product approval determination.
The FDA granted approval of Kymriah to Novartis Pharmaceuticals Corp. The FDA granted the expanded approval of Actemra to Genentech Inc.
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines, and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.
The U.S. Food and Drug Administration today approved Mylotarg (gemtuzumab ozogamicin) for the treatment of adults with newly diagnosed acute myeloid leukemia whose tumors express the CD33 antigen (CD33-positive AML). The FDA also approved Mylotarg for the treatment of patients aged 2 years and older with CD33-positive AML who have experienced a relapse or who have not responded to initial treatment (refractory).
Mylotarg originally received accelerated approval in May 2000 as a stand-alone treatment for older patients with CD33-positive AML who had experienced a relapse. Mylotarg was voluntarily withdrawn from the market after subsequent confirmatory trials failed to verify clinical benefit and demonstrated safety concerns, including a high number of early deaths. Today’s approval includes a lower recommended dose, a different schedule in combination with chemotherapy or on its own, and a new patient population.
“We are approving Mylotarg after a careful review of the new dosing regimen, which has shown that the benefits of this treatment outweigh the risk,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Mylotarg’s history underscores the importance of examining alternative dosing, scheduling, and administration of therapies for patients with cancer, especially in those who may be most vulnerable to the side effects of treatment.”
AML is a rapidly progressing cancer that forms in the bone marrow and results in an increased number of white blood cells in the bloodstream. The National Cancer Institute of the National Institutes of Health estimates that approximately 21,380 people will be diagnosed with AML this year and that 10,590 patients with AML will die of the disease.
Mylotarg is a targeted therapy that consists of an antibody connected to an anti-tumor agent that is toxic to cells. It is thought to work by taking the anti-tumor agent to the AML cells that express the CD33 antigen, blocking the growth of cancerous cells and causing cell death.
The safety and efficacy of Mylotarg in combination with chemotherapy for adults were studied in a trial of 271 patients with newly diagnosed CD33-positive AML who were randomized to receive Mylotarg in combination with daunorubicin and cytarabine or to receive daunorubicin and cytarabine without Mylotarg. The trial measured “event-free survival,” or how long patients went without certain complications, including failure to respond to treatment, disease relapse or death, from the date they started the trial. Patients who received Mylotarg in combination with chemotherapy went longer without complications than those who received chemotherapy alone (median, event-free survival 17.3 months vs. 9.5 months).
The safety and efficacy of Mylotarg as a stand-alone treatment were studied in two, separate trials. The first trial included 237 patients with newly diagnosed AML who could not tolerate or chose not to receive intensive chemotherapy. Patients were randomized to receive treatment with Mylotarg or best supportive care. The trial measured “overall survival,” or how long patients survived from the date they started the trial. Patients who received Mylotarg survived longer than those who received only best supportive care (median overall survival 4.9 months vs. 3.6 months). The second trial was a single-arm study that included 57 patients with CD33-positive AML who had experienced one relapse of disease. Patients received a single course of Mylotarg. The trial measured how many patients achieved a complete remission. Following treatment with Mylotarg, 26 percent of patients achieved a complete remission that lasted a median 11.6 months.
Common side effects of Mylotarg include fever (pyrexia), nausea, infection, vomiting, bleeding, low levels of platelets in the blood (thrombocytopenia), swelling and sores in the mouth (stomatitis), constipation, rash, headache, elevated liver function tests, and low levels of certain white blood cells (neutropenia). Severe side effects of Mylotarg include low blood counts, infections, liver damage, blockage of the veins in the liver (hepatic veno-occlusive disease), infusion-related reactions, and severe bleeding (hemorrhage). Women who are pregnant or breastfeeding should not take Mylotarg, because it may cause harm to a developing fetus or a newborn baby. Patients with hypersensitivity to Mylotarg or any component of its formulation should not use Mylotarg.
The prescribing information for Mylotarg includes a boxed warning that severe or fatal liver damage (hepatotoxicity), including blockage of veins in the liver (veno-occlusive disease or sinusoidal obstruction syndrome), occurred in some patients who took Mylotarg.
Mylotarg received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.
The FDA granted the approval of Mylotarg to Pfizer Inc.
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.
On Aug. 17, 2017, the U.S. Food and Drug Administration approved inotuzumab ozogamicin (BESPONSA, Wyeth Pharmaceuticals Inc., a subsidiary of Pfizer Inc.) for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).
The approval was based on data from INO-VATE ALL (NCT01564784), a randomized (1:1), open label, international, multicenter study in 326 patients with Philadelphia chromosome-negative or Philadelphia chromosome-positive relapsed or refractory B-cell precursor ALL. Patients were required to have ≥5% bone marrow blasts and to have received one or two previous induction chemotherapy regimens for ALL. Patients with Philadelphia chromosome positive B cell precursor ALL were required to have disease that failed treatment with at least one tyrosine kinase inhibitor and standard chemotherapy.
Patients were randomized to receive inotuzumab ozogamicin (n=164) or investigator’s choice of chemotherapy (n=162). Of the initial 218 randomized patients, 35.8% of those who received inotuzumab ozogamicin experienced complete remission (CR) for a median 8.0 months and 89.7% of those patients achieved minimal residual disease (MRD)-negativity. Of the patients who received chemotherapy, 17.4% experienced CR for a median 4.9 months and 31.6% of those patients achieved minimal residual disease MRD-negativity.
The most common adverse reactions occurring in greater than 20% of patients were thrombocytopenia, neutropenia, infection, anemia, leukopenia, fatigue, hemorrhage, pyrexia, nausea, headache, febrile neutropenia, transaminases increased, abdominal pain, gamma-glutamyltransferase increased, and hyperbilirubinemia. The most common (≥2%) adverse reactions reported as the reason for permanent discontinuation were infection, thrombocytopenia, hyperbilirubinemia, transaminases increased, and hemorrhage.
For the first cycle, the recommended dose of inotuzumab ozogamicin for all patients is 1.8 mg/m2 per cycle, administered as three divided doses on day 1 (0.8 mg/m2), day 8 (0.5 mg/m2), and day 15 (0.5 mg/m2). The recommended dosing for subsequent cycles depends on response to treatment. Details are available in the full prescribing information: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761040s000lbl.pdf
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).
Follow the Oncology Center of Excellence on Twitter @FDAOncology.
Check out recent approvals at the OCE’s new podcast, Drug Information Soundcast in Clinical Oncology (D.I.S.C.O.), available at www.fda.gov/DISCO.
People experiencing leukaemia symptoms are suffering in silence. Over half (58%) of leukaemia patients put off visiting their GP for more than a month from when they first start experiencing symptoms
Too many people are unaware of leukaemia symptoms leading them to put off visiting their GP, according to new research from Leukaemia Care. While most (81%) patients experienced symptoms of leukaemia, very few (14%) suspected their symptoms indicated blood cancer, and only 3% expected it.
The report, ‘Living with Leukaemia”, surveyed over 2,000 people living with leukaemia in the UK. It found that over half of leukaemia patients put off visiting their GP for more than a month from when they first started experiencing symptoms. Nearly one in ten (9%) of respondents didn’t see a GP about their symptoms for more than a year.
The research has also highlighted that GPs are struggling to spot leukaemia. Less than half (44%) of respondents felt that their GP had a good understanding of the disease. Worryingly, more than one in ten patients (13% overall, ranging from 8% to 24% across different leukaemia types) were initially treated for something else by their GP.
Leukaemia Care has today warned that this gap in understanding is leading to delays in diagnosis, which severely impacts survival rates and quality of life for leukaemia patients.
Leukaemia symptoms are notoriously vague and non-specific. People commonly experience fatigue, shortness of breath, fever and night sweats, bruising or bleeding, joint or bone pain and sleeping problems. As a result, people with leukaemia are more likely to be diagnosed in an emergency than other cancers. 64% of acute lymphoblastic leukaemia (ALL) cases and 53% of acute myeloid leukaemia (AML) cases are diagnosed following an emergency admission.
Commenting on the research, Zack Pemberton-Whiteley, Head of Campaigns and Advocacy at Leukaemia Care, said: “Leukaemia is notoriously difficult to spot. People with leukaemia have told us how they felt unwell prior to their diagnosis but didn’t see their GP because they didn’t think their symptoms were that serious. It’s so easy to dismiss leukaemia symptoms as feeling a bit run-down or under the weather. We want people to feel empowered to speak to their GP if they have any concerns at all.
“We urgently need to improve leukaemia awareness among the public and GPs so that patients can get a diagnosis and access treatment faster. That’s why Leukaemia Care has launched the Spot Leukaemia campaign – early diagnosis saves lives.”
Dr Ellie Cannon, a London-based GP, said: “I’m supporting the ‘Spot Leukaemia’ campaign this September for Blood Cancer Awareness Month. The campaign seeks to raise awareness amongst the public and medical professionals of the different types of leukaemia, common symptoms and the populations they may affect. Leukaemia can be difficult for GPs to spot, because its relatively rare and symptoms may be vague.”
Kris Griffin, a leukaemia patient, said: “The new job involved a longer commute and I was experiencing some pains in my back. I was also having night sweats and had lost a little weight which, quite frankly, felt totally insignificant. I had no idea that my body was sending out a distress signal. I went to the GP who prescribed paracetamol and wasn’t overly concerned. Still in pain I returned two weeks later and was tested for arthritis. The blood results returned a diagnosis of chronic myeloid leukaemia.”
Leukaemia Care has today released the report ‘Living with Leukaemia’. The report is based on responses from 1320 leukaemia patients identified through the National Cancer Patient Experience 2015 Survey and 699 leukaemia patients from the wider blood cancer community. The report can be accessed online here: www.leukaemiacare.org.uk/living-with-leukaemia
About Leukaemia Care
Leukaemia Care is a national blood cancer support charity. We are dedicated to ensuring that anyone affected by blood cancer receives the right information, advice and support.
A diagnosis of a blood cancer can have a huge impact on someone emotionally, as well as physically. We understand that feelings of shock, anger and loneliness are all common at the time of diagnosis, during treatment and recovery and having someone to talk to, as well as the right information available can be a huge comfort.
We not only support patients, but carers and families too who can often carry a lot of the emotional strain when someone they love is diagnosed with a blood cancer.
We focus on the support that is needed now to help those affected by blood cancer cope during a diagnosis and beyond.
Over 9,500 people are diagnosed with leukaemia in the UK every year3 Leukaemia is a cancer which starts in blood-forming tissue, usually the bone marrow. It leads to the over-production of abnormal white blood cells, the part of the immune system which defends the body against infection.
Are there different types of leukaemia?
There are a number of different types of leukaemia, but the four most common are: