Immunotherapy for Acute Lymphocytic Leukemia (ALL)

(Note: This information is about treating acute lymphocytic leukemia (ALL) in adults. To learn about ALL in children, see Leukemia in Children.)

Immunotherapy is the use of medicines to help a patient’s own immune system recognize and destroy cancer cells more effectively. Some types of immunotherapy are now being used to treat acute lymphocytic leukemia (ALL) in certain situations.

Monoclonal antibodies

Antibodies are proteins made by the body’s immune system to help fight infections. Man-made versions of these proteins, called monoclonal antibodies, can be designed to attack a specific target, such as a protein on the surface of leukemia cells.

Blinatumomab (Blincyto)

Blinatumomab is a special kind of monoclonal antibody because it can attach to 2 different proteins at the same time. One part of blinatumomab attaches to the CD19 protein, which is found on B cells, including some leukemia and lymphoma cells. Another part attaches to CD3, a protein found on immune cells called T cells. By binding to both of these proteins, this drug brings the cancer cells and immune cells together, which is thought to cause the immune system to attack the cancer cells.

This drug is used to treat some types of B-cell ALL, typically after chemotherapy has been tried. It is given into a vein (IV) as a continuous infusion over 28 days. It may be repeated again for more cycles with 2 weeks off in between. Because of certain serious side effects that occur more often during the first few times it is given, the patient usually needs to be treated in a hospital or clinic for the beginning of at least the first 2 cycles.

The most common side effects are fever, headache, swelling of the feet and hands, nausea, tremor, rash, constipation, and low blood potassium levels. It can also cause low white blood cell counts, which increase the risk of serious infection.

This drug can also cause neurologic problems, such as seizures, difficulty in speaking or slurred speech, passing out, confusion, and loss of balance.

Some patients have serious reactions while this drug is being infused. Symptoms can include feeling lightheaded or dizzy (due to low blood pressure), headache, nausea, fever or chills, shortness of breath, and/or wheezing. Let your healthcare team know if you develop any of these symptoms, as this reaction can be life-threatening. If you do have a reaction, the drug will be stopped while the reaction is treated.

Inotuzumab ozogamicin (Besponsa)

This drug is an anti-CD22 antibody linked to a chemotherapy drug. B cells (including some leukemia cells) usually have the CD22 protein on their surface. The antibody acts like a homing signal, bringing the chemo drug to the leukemia cells, where it enters the cells and kills them when they try to divide into new cells.

This drug is used to treat some types of B-cell ALL, typically after chemotherapy has been tried. It is given as an infusion into a vein (IV), once a week for 3 or 4 weeks in a row. This may be repeated for more cycles. 

The most common side effects are low levels of blood cells (with increased risks of infection, bleeding, and fatigue), fever, nausea, headache, abdominal (belly) pain, and high blood levels of bilirubin (a substance in bile).

Less common but more serious side effects can include:

  • Severe liver damage, including veno-occlusive disease (blockage of veins in the liver)
  • Reactions during the infusion (similar to an allergic reaction). You will likely be given medicines before each infusion to help prevent this.
  • Serious or life-threatening infections, especially in people who have already had a stem cell transplant
  • Changes in the rhythm of the heart

CAR T-cell therapy

For this treatment, immune cells called T cells are removed from the person's blood and genetically altered in the lab to have specific receptors (called chimeric antigen receptors, or CARs) on their surface. These receptors can attach to proteins on leukemia cells. The T cells are then multiplied in the lab and given back into the blood, where they can seek out the leukemia cells and attack them.

Tisangenlecleucel (Kymriah) 

This is a type of CAR T-cell therapy that targets the CD19 protein on certain leukemia cells. It can be used in children and young adults up to age 25 to treat B-cell ALL that has come back after treatment or that is no longer responding to treatment.

To make this treatment, T cells are removed from the blood during a process called leukapheresis. Blood is removed through an IV line and goes into a machine that removes the T cells. The remaining blood then goes back into the body. This typically takes a few hours, and it might need to be repeated. The cells are then frozen and sent to a lab, where they are turned into CAR T cells and are multiplied. This can take a few weeks.

For the treatment itself, the patient typically gets chemo for a few days to help prepare the body. Then they get the CAR T cells as an infusion into a vein (IV). Because this treatment can have serious side effects (see below), it is only given in medical centers that have special training with this treatment.

This treatment can have serious or even life-threatening side effects, which is why it needs to be given in a medical center that has special training in its use.

Cytokine release syndrome (CRS): CRS happens when T cells release chemicals (cytokines) that ramp up the immune system. This can happen within a few days to weeks after treatment, and can be life-threatening. Symptoms can include:

  • High fever and chills
  • Trouble breathing
  • Severe nausea, vomiting, and/or diarrhea
  • Severe muscle or joint pain
  • Feeling dizzy or lightheaded

Nervous system problems: This drug can have serious effects on the nervous system, which can result in symptoms such as:

  • Headaches
  • Changes in consciousness
  • Confusion or agitation
  • Seizures
  • Trouble speaking and understanding
  • Loss of balance

Other serious side effects: Other possible side effects can include:

  • Serious infections
  • Low blood cell counts, which can increase the risk of infections, fatigue, and bruising or bleeding

It’s very important to report any side effects to the health care team right away, as there are often medicines that can help treat them.

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Jain N, Gurbuxani S, Rhee C, Stock W. Chapter 65: Acute Lymphoblastic Leukemia in Adults. In: Hoffman R, Benz EJ, Silberstein LE, Heslop H, Weitz J, Anastasi J, eds. Hematology: Basic Principles and Practice. 6th ed. Philadelphia, Pa: Elsevier; 2013.

National Comprehensive Cancer Network. NCCN Practice Guidelines in Oncology: Acute Lymphoblastic Leukemia. V.1.2018. Accessed at www.nccn.org/professionals/physician_gls/pdf/all.pdf on July 23, 2018.

Terwilliger T, Abdul-Hay M. Acute lymphoblastic leukemia: A comprehensive review and 2017 update. Blood Cancer J. 2017;7(6):e577.

Last Medical Review: October 17, 2018 Last Revised: October 17, 2018