Immunotherapy in Leukemia PDF

Immunotherapy: quick facts ** Immunotherapy trains immune system cells to destroy cancer cells....

Immunotherapy: quick facts ** Immunotherapy trains immune system cells to destroy cancer cells. ** It may cause fewer side effects than traditional treatments, as it does not kill healthy cells. **It may also reduce the risk of cancer coming back and improve remission rates. ** However, immunotherapy for leukemia is a new treatment and does not work for all types of leukemia. https://www.medicalnewstoday.com/articles/immunotherapy-for-leukemia 6 What is immunotherapy? How does it work? Immunotherapy is a type of treatment for leukemia that works by prompting the body’s own immune system to identify and destroy cancerous cells. Ordinarily, the immune system protects the body against bacteria, viruses, allergens and other pathogens. However, some cancer cells can avoid destruction by tricking the immune system into treating them like healthy cells. But, by programming the immune system to locate and attack cells that have cancerous characteristics (such as certain tumor-specific proteins on their surfaces), immunotherapy can be used as a treatment for leukemia and other hematological malignancies (blood cancers). https://www.moffitt.org/cancers/leukemia/treatment/immunotherapy/#:~:text=Immunotherap y%20is%20a%20type%20of,viruses%2C%20allergens%20and%20other%20pathogens. 7 8 Which types of leukemia can be treated with immunotherapy? Not all leukemias are responsive to the same type of immunotherapy, and immunotherapy may not be appropriate for some leukemias. There are four different types of leukemia: 1. Acute lymphocytic leukemia (ALL) – This is the most common form of leukemia diagnosed in children. 2. Acute myeloid leukemia (AML) – This is the most common type of leukemia affecting both adults and children. 3. Chronic lymphocytic leukemia (CLL) – This is the most prevalent form of chronic leukemia affecting adults. 4. Chronic myeloid leukemia (CML) – This slow-progressing type mainly affects adults and may produce few or no symptoms for months or even years. https://www.moffitt.org/cancers/leukemia/treatment/immunotherapy/#:~:text=Immunotherapy%20i s%20a%20type%20of,viruses%2C%20allergens%20and%20other%20pathogens. 9 Most immunotherapies that are currently available are designed to treat ALL and CLL. However, new therapies are being developed every day and tested in clinical trials, so there may eventually be immunotherapies to treat all types of leukemia Immunotherapy is an extremely effective treatment for some leukemia patients, though it can be difficult to determine which patients will respond to therapy. Using circulating tumor DNA (ctDNA) as a guide to help determine whether patients are responding. https://www.moffitt.org/cancers/leukemia/treatment/immunotherapy/#:~:text=Immunotherapy%20i s%20a%20type%20of,viruses%2C%20allergens%20and%20other%20pathogens. 10 Side effects of leukemia immunotherapy The side effects of immunotherapy vary based on the type of immunotherapy delivered, type of leukemia, the patient’s overall health and additional factors. Some people experience significant side effects from immunotherapy while others do not have any side effects. Common side effects of immunotherapy include: Nausea Diarrhea Fever Constipation Chills Skin rash Tiredness Stomach pain Headache Muscle, joint or bone pain Shortness of breath 11 More serious side-effects Some patients may experience more serious side effects, such as reactions to infusions (which are similar to allergic reactions), infections, low blood cells counts or nervous system problems such as: Changes in level of consciousness Confusion Agitation Seizures Trouble speaking and understanding speech Loss of balance https://www.moffitt.org/cancers/leukemia/treatment/immunoth erapy/#:~:text=Immunotherapy%20is%20a%20type%20of,viruses %2C%20allergens%20and%20other%20pathogens. 12 When might a physician recommend immunotherapy for treating leukemia? When considering immunotherapy as a treatment for leukemia, it’s important to evaluate a number of patient-specific factors to determine which option to use. Hematologists and oncologists create individualized treatment plans that feature a wide variety of treatments. Immunotherapy may be offered as a solo treatment or in combination with other treatments (such as chemotherapy) and sometimes as follow-up to chemotherapy (i.e. “maintenance” therapy). Many types of immunotherapy are also offered in the setting of a clinical trial. https://www.moffitt.org/cancers/leukemia/treatment/immunotherapy/#:~:text=Immunoth erapy%20is%20a%20type%20of,viruses%2C%20allergens%20and%20other%20pathogens. 13 https://www.cancerresearchuk.org/about- cancer/treatment/immunotherapy/types 14 CAR–T cell therapy 15 Who should consider CAR-T cancer therapy? CAR T therapy is currently only approved for patients with certain types of blood and bone marrow cancers. Generally speaking, a patient may be eligible for CAR-T therapy if other forms of treatment, such as chemotherapy, have been unsuccessful or were not an option. Studies have shown that in certain cases when another type of cancer treatment stops working, CAR T therapy can produce favorable outcomes. https://www.moffitt.org/treatments/immunotherapy/car-t-therapy/ 16 How does CAR – T cell therapy work? Next, chimeric antigen receptor (CAR)—a special receptor that binds to certain proteins on At the lab, the patient’s cancer cells—will be added to the T-cells will be separated patient’s T cells from rest of their blood The patient’s T cells will then be duplicated and prepared for treatment a sample of the patient’s blood will be taken and sent to a lab https://www.cancerresearchuk.org/about-cancer/treatment/immunotherapy/types/CAR-T-cell-therapy 17 CAR–T Cell Therapy drugs Tisagenlecleucel (Kymriah®): a CD19-targeting CAR-T cell immunotherapy; approved for subsets of children and young adult patients with acute lymphoblastic leukemia (ALL). Indicated for relapsed or refractory (not responding to treatment) ALL children and young adults. Brexucabtagene autoleucel (Tecartus ): a CD19-targeting CAR T-cell immunotherapy; approved for subsets of adult patients with acute lymphoblastic leukemia (ALL) https://www.cancerresearch.org/cancer-types/leukemia 18  Does CAR–T cell therapy produce side effects? CAR-T therapy can cause some side effects as the CAR-T cells grow and attack the cancer, causing high amounts of inflammation in the body, similar to how the body responds to infections. 1. Neurotoxicity syndrome: neurological difficulties such as confusion, stupor (near-unconsciousness) and difficulty understanding language and speaking 2. Cytokine release syndrome (CRS), which can cause fever, chills, dizziness, lightheadedness, headache, increased heart rate, low blood pressure, difficulty breathing, nausea, vomiting, diarrhea, muscle pain, joint pain, fatigue, shortness of breath and confusion Because CAR-T therapy has the potential to cause side effects, it’s important that patients be closely monitored while they’re recovering (the recovery process generally https://www.moffitt.org/treatments/immunotherapy/car-t-therapy/ takes approximately 30 days). 19 Management of CAR-T cell therapy side-effects Among the recommendations are supportive care as a first line of care for short- term toxicities in most patients followed by drug interventions for those who don’t respond adequately. For patients with prolonged or severe CRS, tocilizumab alone or with a corticosteroid is recommended. A combination of corticosteroids and supportive care is recommended for patients with moderate to severe immune neurotoxicity syndrome, given the potential for rapid decline in these patients. Once symptoms improve to grade 1, steroids should be rapidly tapered (gradually reduced). 20 https://www.cancerresearchuk.org/about- cancer/treatment/immunotherapy/types 21 Monoclonal antibodies Monoclonal antibodies (mAbs) are immune system proteins created in the lab that are designed to bind to specific targets on cancer cells. Some monoclonal antibodies mark cancer cells so that they will be better seen and destroyed by the immune system. Also, known as “therapeutic antibodies”. The mAbs that can be used to treat leukemia are: Gemtuzumab ozogamicin  pediatric AML Blinatumomab  ALL Inotuzumab ozogamixin) (ALL) Moxetumomab pasudotox (Lumoxiti) (hairy cell leukemia) alemtuzumab (Campath) (CLL) rituximab (Rituxan) (CLL) https://www.healthline.com/health/leukemia/im munotherapy-for-leukemia#when-its-used 22 Blinatumomab (Blincyto) Blinatumomab is a monoclonal antibody called a bispecific T-cell engager (BiTE). It simultaneously attaches to T-cells and cancer cells, enabling T-cells to easily find and destroy the cancer cell by bringing them closer together. Indications: BLINCYTO is indicated for the treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) in adults and children. BLINCYTO is indicated as monotherapy for the treatment of paediatric patients aged 1 year or older with high-risk first relapsed Philadelphia chromosome negative CD19 positive B-precursor ALL as part of the consolidation therapy. 23 Side-effects of Blinatumomab Most common side-effects Serious side-effects infection* Severe neurologic adverse events fever very high fever headache low level of neutrophils low level of red blood cells liver problems infusion-related reaction* irregular heart rhythm inflammation of the pancreas 24  Immunomodulators https://www.cancerresearchuk.org/about- cancer/treatment/immunotherapy/types 25 Immunomodulators (Cytokines) Immune system modulators, which enhance the body’s immune response against cancer. Interferon alfa-2a: a cytokine that targets the IFNAR1/2 pathway; approved for subsets of patients with hairy cell leukemia and Philadelphia chromosome positive chronic myeloid leukemia (CML) Interferon alfa-2b: a cytokine that targets the IFNAR1/2 pathway; approved for subsets of patients with hairy cell leukemia and aggressive follicular non-Hodgkin lymphoma https://www.cancerresearch.org/cancer-types/leukemia 26 https://www.cancerresearchuk.org/about- cancer/treatment/immunotherapy/types 27 Immune checkpoint inhibitors Drugs that block immune checkpoints. These checkpoints are a normal part of the immune system and keep immune responses from being too strong. By blocking them, these drugs allow immune cells to respond more strongly to cancer. Example: PD1 inhibitors ipiliolumab and pembrolizumab (under clinical evaluation for AML) Vaccines to treat cancer Drugs which work against cancer by boosting your immune system’s response to cancer cells. Treatment vaccines are different from the ones that help prevent disease. 28 Success rate of immunotherapy for leukemia The effectiveness of immunotherapy for leukemia can depend on many different factors. These include: type of leukemia you have extent (stage) of the leukemia kind of immunotherapy used other types of cancer treatments received age and overall health https://www.healthline.com/health/leukemia/immunotherapy-for- leukemia#when-its-used 29 Immunotherapy drug improves outcomes for some children with relapsed leukemia Children can also develop leukemia. According to the American Cancer Society Trusted Source, about 3 out of 4 leukemias in children are ALL while most of the remaining instances are AML. Chronic leukemias are quite rare in children. Immunotherapy for pediatric leukemia: Blinatumomab (Blincyto), a monoclonal antibody used for ALL Gemtuzumab ozogamicin (MyloTarg), a conjugated monoclonal antibody used for AML Tisagenlecleucel (Kymriah), a CAR T-cell therapy used for ALL https://www.healthline.com/health/leukemia/immunotherapy-for- leukemia#when-its-used 30