CAR T-cell therapies in treating lymphoma: Pros and cons

Catherine Bollard, MD, director of the Center for Cancer and Immunology Research at Washington, D.C.-based Children’s National Health System, discussed immunotherapy for non-Hodgkin’s lymphoma at the 2017 American Society of Hematology (ASH) annual meeting, which took place in Atlanta from December 9 to 12.

Her talk focused on chimeric antigen receptor (CAR) T cells, which are genetically modified for the treatment of lymphoma, and antigen-specific T-cell treatments; the second type of T cells are trained in the laboratory to recognize and kill tumors-in this case, lymphoma.

Managed Healthcare Executive (MHE) discussed the ASH presentation with Bollard. What follows are some highlights of that conversation.

MHE: What’s the success rate with CAR T-cell treatments?      

Bollard: Across the three pharmaceutical studies, over 200 patients have received CAR T cells [for non-Hodgkin’s lymphoma], 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.

This really does indicate that there’s potency with these products, but longer follow up is needed. Progression-free survival and overall survival is needed before we could truly compare across these different trials. However, we all agree that there are still appreciable toxicities related to CAR T-cells that need to be mitigated.

MHE: What are the remaining obstacles to overcome with the CAR T-cell therapies?

Bollard: The expense of these drugs is one. Who’s going to pay for the drugs? There are currently insurance issues with this.

(Fred Locke, MD, a medical oncologist at Moffitt Cancer Center, tells MHE that Kymriah (tisagenlecleucel) from Novartis costs $475,000, and Yescarta (axicabtagene ciloleucel) from Gilead costs $373,000.)

Next: How should payers pay for CAR T-cell therapies? 

MHE: How would you like payers to pay for the CAR T-cell therapies?

Bollard:  CAR T-cell therapies have remarkable potency, and we’re seeing that in the patients who have already relapsed, in some cases, up to 10 times. The cost of that alone-treating a patient with 10 lines of therapy-is a lot. The CAR T-cell approach could be brought up early in the treatment process as the initial therapy.

If we could bring CAR T-cell therapies into the disease treatment process much earlier, that would be remarkably cost effective. 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.

Now that the Novartis product has been approved by the FDA, the pharmaceutical company’s next clinical trial will bring that therapy out much earlier in the disease process.

If I were a drug company developing a CAR T-cell therapy, I would look at my competing therapy and make sure my new therapy doesn’t cost significantly more. And in this instance, the best competing therapy is a bone marrow transplant, which is relevant for acute lymphoblastic leukemia (ALL).

MHE: Tell me more about the antigen-specific T cells and how they work.

Bollard: We don’t genetically modify these cells. We basically train the cells in the laboratory to recognize the different tumor proteins expressed by the tumor cells. We started with the Epstein-Barr virus (EBV)-associated lymphomas; these are lymphomas that develop in patients, even after bone marrow transplants, solid organ transplants, or in immunocompetent patients.

The response rate using EBV-specific T-cells is up to 90%, depending on the patient group. We can move this to an off-the-shelf product because there are multiple studies that have used banks of these T-cells; they have shown remarkable safety and efficacy. This has not been shown when that strategy was tried with CAR T cells.

MHE: What are the advantages and disadvantages of both therapies?

Bollard: The CAR T cells are much more expensive, and they require much more modification. The antigen-specific T cells are cheaper and there’s no genetic modification.

That means the CAR T-cell approach is complex and requires a lot of regulatory oversight. The antigen-specific T cells don’t require regulatory oversight because there’s no gene modification.

But there’s no doubt that the CAR T cells are showing remarkable efficacy in a patient population without many options. On the other hand, the antigen-specific T cells have shown efficacy but these are in a much smaller number of trials-and without significant support from big pharmaceutical companies.

Finally, the CAR T cells are associated with life-threatening toxicities. The antigen-specific T cells have a severe toxicity rate of 1.2%.

MHE: Is cost as much of a factor with the antigen-specific T cells?

Bollard: None of these products have been licensed. 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.

Because the antigen-specific T cells are more cost effective, they may be more attractive to payers. There are some pharmaceutical companies embracing this therapy, but they’re lagging behind the CAR T-cell therapies.