ASH 2023: The Risk of Secondary Cancers with CAR-T Therapy

Over the last week, I've heard from several myeloma patients, caregivers, and patient advocates about the FDA's investigation into secondary cancers associated with CAR T-cell therapy. 

As the news of this investigation spread right before the American Society of Hematology (ASH) conference, we knew this would be a common question and hot topic in sessions regarding myeloma immunotherapy treatment. 

Within the first hour of the first meeting I attended, our hypothesis was proven right, and the question was asked, "How does the FDA's investigation of CAR-T cell therapy secondary cancer risks affect how doctors are approaching CAR T-cell therapy in their clinics?" 

In the second meeting I attended, the same issue was brought up, "How concerned should we be about the [CAR T-cell secondary cancer risk] data that the FDA is investigating?" 

Because these are questions that I know many in the myeloma community share, I wanted to address the concerns with the words of the doctors themselves who presented at today's ASH meetings. 

Krina K. Patel, MD, MSc from MD Anderson Cancer Center, shares,

"We knew [secondary cancers] were a potential [risk], and that's why patients on these clinical trials [and in standard of care treatment] are followed for fifteen years. There are 19 patients out of 7500 [that had these secondary cancers develop]. When we look at SEER data, at least in lymphoma, we see a higher risk of T-cell lymphomas and leukemias as secondary cancers [than we are seeing in myeloma]. It's important to put this in context. Of course, it's important to look at this and see if there is anything we can do to change that, but the risk of myeloma is more likely to cause problems if they are not getting adequate responses. Clinically, we know that they have the same risk of secondary cancers even without CAR-T. It will be important to see what the data shows." 

Prof. Mohamad Mohty from Saint-Antoine Hospital and Sorbonne University in Paris, France, adds, 

"More patients are more likely to die from their disease, myeloma, than they are to die of the secondary cancers that are being investigated. At the time, I don't believe there is a reason [to alter CAR-T treatment] as we are currently offering it. It's a work in progress." 

Dr. Hans Lee, also treating patients at the University of Texas MD Anderson Cancer Center, contributes, 

"I agree with my colleagues. This an important [issue] to track and study, but at the end of the day, if you were to ask me, does this alter the risk/benefit ratio [of CAR-T cell therapy], I would say no. The risk of myeloma resulting in bad complications [without proper treatment] is very high... so at this point with the data available, the risk/benefit ratio has not been altered in my mind." 

Nikhil C. Munshi, MD, from the Jerome Lipper Multiple Myeloma Center and Harvard Medical School in Boston, Massachusetts, concluded, 

"There is a risk of secondary cancers with lenalidomide [as well]...the treatments that we have are so effective in treating myeloma. Because of this success, and all the panel seems to agree, there is no reason to alter the therapy as is right now with the data that we have." 

In a later session, Dr. Ajai Chari from UCSF (previously at Mount Sinai) and Sikander Ailawadhi, M.D., who treats myeloma at Mayo Clinic in Florida, shared their thoughts on the topic. 

Dr. Ailawadhi shares, 

"Any one cancer increases your risk for subsequent cancer. We educate all of our patients on this subject. A lot of treatments are associated with a higher risk of secondary malignancies, [including lenalidomide], but we still use those medications [because they are successful in treating myeloma]..." 

Dr. Chari added, 

"The FDA is collecting data; they are not trying to stop us from using these products... one of the combined data sets that they are looking at has one out of 600 myeloma patients that developed a secondary malignancy after their CAR-T." 

Dr. Chari went on to explain that further investigation showed this one myeloma patient's T-cells that had been re-engineered, in other words, their original T-cells, showed indications of secondary cancer before the cells were re-engineered, but it wasn't caught at the time. Therefore, the CAR-T couldn't have been the cause of the secondary malignancy. 

In addition, the specialists across the board shared the fact that it's incredibly hard to pinpoint where the secondary cancer is actually coming from.

Is it simply because they are at higher risk for another cancer, due to the fact that they have myeloma? Could it have been a previous therapy before their CAR-T therapy that caused the malignancy to develop? (Many of these patients that the FDA are investigating were heavily pre-treated before receiving CAR-T). Could it have to do with certain genetic risks? There are many unknowns. 

In the Saturday evening ASH session, the topic came up again: 

Dr. Noopur Raje from Massachusetts General Hospital shares, "These incidences [of secondary melignancies] are so rare, it's not going to currently affect the way that we are administrating CAR T-cell therapy." 

Dr. Amrita Krishnan from City of Hope added her insight on the issue,  "The devil is in the details, and we just don't know [about the biology] yet. What could be causing these secondary malignancies? It's too early to tell." 

In conclusion, the general consensus among myeloma specialists is that while the risk of secondary cancers after CAR-T is a serious issue and something worth looking into, it's not something that is going to change the way that they are currently administering or recommending CAR T-cell therapy to patients. 

The one thing that will change is that the risk of secondary cancers or malignancies will now be a consideration that they talk to their patients about who are considering CAR-T therapy as their next line (or a future line) of treatment. 

Stay tuned as we will continue to update our myeloma community on this important topic as more information emerges.

Would you like to watch ASH 2023 myeloma research interviews from the investigators themselves? Click "ASH 2023" here: HealthTree University Conference Coverage

Dr. Rahul Banerjee (and team's) official response to CAR-T Secondary Cancers Issue