Ten Things Health Execs Should Know about Lymphoma
New treatment approaches could lead to even higher costs associated with lymphoma. However, experts say these treatments hold great promise and could reduce costs in the long-term.
An estimated 80,500 people received a lymphoma diagnosis last year, according to the American Cancer Society. It’s one of the most common types of cancer and treatment associated with it contributes to the estimated $88 billion spent treating all cancers in the United States annually. New treatments could lead to even higher costs for lymphoma. However, experts say these treatments hold great promise and could reduce costs in the long-term. Jacob Chaffee, PharmD, clinical pharmacist for emerging therapies at Blue Cross Blue Shield of Michigan, noted during his presentation at the AMCP Annual Meeting, in Boston April 25, that more than 45 novel cancer therapies have been approved by the FDA since 2013. And more than 600 molecules are in a late-stage pipeline. Read on to find out more.
Lymphoma is the most common blood cancer in adults, and the third most common cancer among children, according to the American Cancer Society. Non-Hodgkin lymphoma (NHL) is the most common type, and accounts for about 4% of all cancers in the U.S.
NHL and the other most common type, Hodgkin lymphoma-which affected an estimated 8,260 people in 2017-are further broken down into several different lymphoma subtypes (more than 90 of them, according to The Lymphoma Research Foundation). Common subtypes of NHL are diffuse large B-Cell lymphoma and follicular lymphoma.
Research is being conducted to better understand how genes play a role in lymphoma development and treatment. One example is an international research effort led by Duke Cancer Institute on diffuse large B-cell lymphoma. The researchers used whole exome sequencing to identify 150 genetic drivers and see if there were any correlations between the genes and patient response to therapies. "We have very good data now to pursue new and existing therapies that might target the genetic mutations we identified. Additionally, this data could also be used to develop genetic markers that steer patients to therapies that would be most effective,” said Sandeep Davé, MD, professor of medicine at Duke and coauthor of the study, according to the Duke Cancer Institute.
In August, the FDA approved Kymriah (tisagenlecleucel), the first chimeric antigen receptor (CAR) T-cell therapy for certain pediatric and young adult patients with a form of acute lymphoblastic leukemia. In October, it approved Yescarta (axicabtagene ciloleucel (Yescarta), developed by Kite Pharma, for certain types of non-Hodgkin lymphoma. In CAR T-cell therapy, a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells, according to the National Cancer Institute. The therapy works by removing T cells from a patient’s blood, adding the gene for a special receptor that binds to a certain protein on the patient’s cancer cells in the laboratory, and then given to the patient by infusion. The special receptor is called a CAR.
Catherine Bollard, MD, director of the Center for Cancer and Immunology Research at Washington, D.C.-based Children’s National Health System, discussed CAR-T therapy for non-Hodgkin’s lymphoma at the 2017 ASH annual meeting. She reviewed three pharmaceutical studies, and told Managed Healthcare Executive (MHE) that over 200 patients have received CAR-T cells for the disease, with an overall response rate of 53% to 82%. “I stacked these three studies together and what’s really remarkable is that the six-month complete remission rate across all the studies is almost identical-ranging from 30% to 37% [for complete remission] and ranging from 37% to 41% overall response rate at six months,” said Bollard. “This really does indicate that there’s potency with these products, but longer follow up is needed.”
Frederick Locke, MD, a medical oncologist at Moffitt Cancer Center, was principal investigator for Kite’s ZUMA-1 clinical trial for the treatment of patients with chemorefractory aggressive B-cell non-Hodgkin lymphoma. The study included 110 lymphoma patients, whose tumors were growing even though they were receiving chemotherapy, who were treated with Yescarta. Locke recently told MHE that these were “very refractory patients” and historical data holds that they should have no more than six months to live. With one infusion of CAR-T cells, 82% of these patients had an objective response, and over 50% had a complete disappearance of their lymphoma. Also, with a median follow up of almost nine months, 44% of patients remained in remission, he said.
The drugs alone for CAR-T therapy can cost between $350,000 and $500,000-and that doesn’t include the cost of treating patients in hospitals and their follow-up care. During his presentation, Chaffee broke down the total cost of care associated with CAR T. He said it could range from $523,000 to $795,000 per case. The breakdown of those costs includes:
- Drug cost, which can range from $373,000 to $475,000
- Administration and monitoring, which can range from $50,000 to $120,000
- Adverse events, which can range from $100,000 to $200,000
While he acknowledges the high cost of these therapies, Lee Schwartzberg, MD, chief of the division of hematology and professor of medicine at the University of Tennessee, recently told Managed Healthcare Executive that he’s troubled by the amount of variation he’s observed with payers’ approach to reimbursement. “This is transformative therapy, and we really would like to see every payer [realize] the evidence and pay for this type of therapy,” said Schwartzberg, who helped develop a white paper for the Association of Community Cancer Centers on immuno-oncology. “There shouldn’t be as much variation in coverage as we’re seeing.”
Bollard told MHE that CAR T-cell therapies have remarkable potency. To demonstrate, she noted that some patients with NHL have already relapsed up to 10 times. The cost of that alone-treating a patient with 10 lines of therapy-is a lot, she said. The CAR-T approach could be brought up early in the treatment process as the initial therapy, and therefore, mitigate some of the costs associated with continual relapses, she said. “If we could bring CAR T-cell therapies into the disease treatment process much earlier, that would be remarkably cost effective,” said Bollard. “Then you wouldn’t be dealing with all the relapses. If you treat patients early in their disease process, the toxicity is much less as well; that means the cost of managing the toxicity would be reduced.”
Bollard noted that with this type of therapy, cells aren’t genetically modified as they are with CAR-T therapy. “We basically train the cells in the laboratory to recognize the different tumor proteins expressed by the tumor cells,” she said. As a result, the antigen-specific T-cell approach is less complex and does not require regulatory oversight because there’s no gene modification, said Bollard. It’s also less expensive. The academic cost of manufacturing a CAR-T cell is $18,000, and the cost to generate an antigen-specific T cell is about $8,000, she said. Finally, the CAR-T cells are associated with life-threatening toxicities. The antigen-specific T cells have a severe toxicity rate of 1.2%.
In 2017, there were an estimated 1,070 deaths from Hodgkin lymphoma and 20,140 from NHL, according to the American Cancer Society. Due to treatment improvements the death rate has been declining since 1975 for Hodgkin and since the mid-90s for NHL. In fact, between 2005 and 2014, rates decreased by almost 4% per year for Hodgkin lymphoma and by 2% per year for NHL, according to the society. New treatments, such as CAR-T therapies, could help bring about more patient outcome improvements.