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ImmunotherapyLymphoma

CAR T-Cell Therapy a Promising Option for Patients with Certain Types of B-Cell Lymphoma

“CAR T-cell therapy provides an exciting and additional option for patients who have failed more traditional regimens,” says Dr. Gwen Nichols, Chief Medical Officer for Leukemia & Lymphoma Society.
June 2018 Cancer Immunotherapy
Kristen Chanley

After decades of development, gene therapy, also called “CAR T-cell therapy,” is now a reality for patients with certain types of large B-cell lymphoma, a specific variant of non-Hodgkin lymphoma (NHL).

CAR T-cell therapy is a new type of immunotherapy that involves modifying the patient’s own immune cells (or T-cells) so that those cells will be able to identify and attack cancer cells. Currently, 2 new CAR T-cell therapies are approved by the FDA for patients with diffuse large B-cell lymphoma (DLBCL)—the most common type of NHL in adults—whose disease is refractory (not responding to treatment) or relapses (returns) after treatment, which can be the case for as many as half of the patients with DLBCL.1

The first CAR T-cell therapy to receive FDA approval for patients with lymphoma was Yescarta (axicabtagene ciloleucel), which was the second cancer gene therapy ever approved in the United States, marking a new milestone in the treatment of patients with lymphoma.

Commenting on this approval, Peter Marks, MD, PhD, Director of the FDA’s Center for Biologics Evaluation and Research, said, “The approval of Yescarta brings this innovative class of CAR T-cell therapies to an additional group of cancer patients with few other options—those adults with certain types of lymphoma that have not responded to previous treatments.”2

Gwen Nichols, MD, Chief Medical Officer for the Leukemia & Lymphoma Society (LLS), is also enthusiastic about the potential of CAR T-cell therapy for patients with lymphoma.

“CAR T-cell therapy provides an exciting and additional option for patients who have failed more traditional regimens, especially for DLBCL, which can be a pretty aggressive form of lymphoma,” Dr. Nichols said in an interview with CONQUER magazine.

First CAR T-Cell Therapies for Lymphoma

The first 2 cancer gene therapies were approved in 2017—1 for lymphoma and 1 for leukemia.

The first CAR T-cell therapy approved by the FDA was Kymriah (tisagenlecleucel), which was first approved in August 2017 for pediatric patients with acute lymphoblastic leukemia (or ALL) and then in May 2018 for adults with several types of large B-cell lymphoma, including relapsed or refractory DLBCL, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, or DLBCL arising from follicular lymphoma. In the clinical trial that led to the approval of Kymriah, 50% of those who received Kymriah responded to therapy.3

The second CAR T-cell therapy, Yescarta, was approved by the FDA in October 2017 for adults with several types of B-cell lymphoma, including relapsed or refractory DLBCL, high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma. In the clinical trial that led to the approval of Yescarta, of patients who received Yescarta, 72% responded to it.2

A Balancing Act

Before using either of these gene therapies, patients with relapsed or refractory B-cell lymphoma could use other chemotherapy regimens, have an autologous stem-cell transplant, or even (for younger patients) an allogeneic stem-cell transplant, Dr. Nichols said.

“There are many options in addition to CAR T-cell therapy, and it’s a balancing act with the patient and their healthcare provider to decide what makes the most sense for each individual patient,” Dr. Nichols said.

However, among patients whose tumor initially responded to other treatment regimens, including transplant, the cancer will eventually relapse in about half of them,1 requiring a new treatment option, such as CAR T-cell therapy.

How CAR T-Cell Therapy Works

To create a CAR T-cell therapy, scientists have to collect (or harvest) T-cells from the patient and send them to the lab. There, the cells are genetically engineered to create the CAR protein on the surface of the cells. These CAR proteins allow the T-cells to recognize a specific antigen, such as CD19, on the cancer cells.

Once the engineered CAR T-cells are created, they are sent back to the hospital to infuse them back into the patient’s blood.

“It takes many weeks to harvest cells, prepare them, multiply them, freeze them, and send them back,” said Dr. Nichols. “The current process is expensive and requires many steps, so one aspect of CAR T-cell therapy that patients need to consider is whether they can afford the time necessary for this treatment process.”

In addition, Dr. Nichols advises patients to learn about the potential side effects of CAR T-cell therapy.

Potential Side Effects

As with any cancer treatment, including immunotherapy, CAR T-cell (or gene) therapy has potential risks. In fact, the side effects of CAR T-cell therapy can be significant, and the most serious side effect is called “cytokine release syndrome.” The cytokine release syndrome occurs as a reaction to the foreign cells being infused into the patient through the CAR T-cell therapy, Dr. Nichols said.

“The patient’s body releases cytokines, the body’s internal system of inflammation, almost like an allergic reaction,” she said. Although this reaction can be severe, causing low blood pressure and high fevers, Dr. Nichols pointed out that doctors are becoming aware of this possibility and can now treat it with an approved therapy.

“It’s not something minor, but we have a lot more understanding of it and can be prepared. There are therapies and treatments that can be given to treat this side effect,” she explained.

In August 2017, with the approval of Kymriah, the FDA also approved the first drug—Actemra (tocilizumab)—for the treatment of cytokine release syndrome caused by a CAR T-cell therapy.

Other serious side effects associated with CAR T-cell therapy include neurologic problems, such as confusion, seizures, or severe headaches.4 The potential side effects of CAR T-cell therapy should not be taken lightly, and they may make CAR T-cell therapy not the right option for some patients, Dr. Nichols advised.

“An adverse reaction to the treatment can cause patients to be in the intensive care unit for a day or 2 during treatment,” she said. “For a very sick patient, that can be the straw that breaks the camel’s back.”

Important Tips

Dr. Nichols reminds patients that no treatment decisions should ever be made without a thorough discussion with their healthcare provider and a multidisciplinary team, but patients really need to look at their treatment options from all angles.

“Because this breakthrough is so new, doctors are very excited about the potential of this therapy, but the patients need to understand what the current data are regarding how long they are likely to stay in remission after this therapy,” Dr. Nichols said. “Patients need to be realistic about where this therapy is in development, and what the current status is when making their decision.”

Patients should also consider whether CAR T-cell therapy, either Yescarta or Kymriah, will be covered by their insurance. In addition, only certain hospitals are currently prepared to administer this therapy, and they often have waiting lists.

“This is a very expensive treatment, and patients need to understand what their responsibility is,” Dr. Nichols advised. “Doctors are often thinking about what is best for the patient scientifically, but not necessarily financially, so it’s important for patients to initiate these conversations.”

The Future

The availability of the new CAR T-cell therapies has proved to be a major breakthrough for patients with lymphoma. Dr. Nichols believes that these 2 new immunotherapies are only the tip of the iceberg.

“If we could identify the patients who are unlikely to be cured by our current standards, those are the people who might benefit from receiving CAR T-cell therapy earlier,” Dr. Nichols said. “But until we know the long-term effects, or the likelihood that this therapy might be curative for someone, it’s a hard hurdle to pass.”

Researchers are exploring different ways to stimulate the immune system, and organizations such as LLS are funding research to find ways to improve the efficiency of the CAR T-cell process, while lessening the associated risks.

“If we didn’t have to harvest the cells, manipulate them, and put them back into the patient, it would be better,” Dr. Nichols said.

Dr. Nichols sees great potential for CAR T-cell therapy, anticipating its growing use in the coming years. Despite its current limitations, CAR T-cell therapy has marked a new era in immunotherapy and the personalized treatment of cancer.

References

1. Schuster SJ, Svoboda J, Chong EA, et al. Chimeric antigen receptor T cells in refractory B-cell lymphomas. New England Journal of Medicine. 2017;377(26):2545-2554.
2. US Food and Drug Administration. FDA approves tisagenlecleucel for adults with relapsed or refractory large B-cell lymphoma. May 1, 2018. www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm606540.htm.
3. US Food and Drug Administration. FDA approves CAR-T cell therapy to treat adults with certain types of large B-cell lymphoma. October 18, 2017. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm581216.htm.
4. American Cancer Society. CAR T-cell therapies. www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/car-t-cell1.html.

Key Points

  • The first 2 CAR T-cell therapies for patients with lymphoma are Yescarta and Kymriah
  • CAR T-cell therapy is expensive, so patients should make sure it will be covered by their insurance
  • The potential side effects of CAR T-cell therapy can be significant; the most serious effect is cytokine release syndrome
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Last modified: July 23, 2018

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