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Ask The Doctor Q4 2020: CAR-T Edition

In science and medicine, information is constantly changing and may become out-of-date as new data emerge. All articles and interviews are informational only, should never be considered medical advice, and should never be acted on without review with your health care team.

By Brian Koffman, MDCM (retired), MSEd.

CAR-T-specific questions submitted by readers and answered by the CLL Society Medical Advisory Board

Remember that we cannot give medical advice and any suggestions should be reviewed with your treating doctors.

By Brian Koffman, MDCM (retired), MSEd.

  1. Has there been any trials of CAR-T with Richter’s Syndrome?

Answer from Dr. Koffman:  At the American Society of Hematology (ASH) Annual meeting in December 2020, a CAR-T trial for Richter’s Transformation was presented that saw six of nine patients respond.  Most promising.

  1. What are the prospects for FDA approval, and when?

Answer from Dr. Koffman:  Predicting what the FDA will do is fraught, but based on the data presented at ASH, there is reason to believe we may see approval of liso-cel in 2021.  Fingers crossed.

  1. Is it likely that there will be CAR-T trials for CLL patients who have not already tried, and exhausted, the standard frontline therapies?

Answer from Dr. Koffman:  CAR-T approval at first is likely to only be for patients having already tried, and exhausted, the standard frontline therapies.  That may change over time as it is likely to be more effective when used sooner and may spare patients other therapies.  This should be an active area of research soon, but first it must be approved in CLL.

  1. Is CAR-T only available in clinical trials?

Answer from Dr. Koffman:  Until it is approved by the FDA, CAR-T is only available to CLL patients through clinical trials, but that should change.  CAR-T therapies are already approved for other blood cancers.

  1. How do you enroll in the clinical trial?

Answer from Dr. Koffman:  Ask your healthcare team about trials. is a good online source.  Search for CAR-T and CLL.  You can sort by location and other variables.  Once you find a trial that seems like a fit, a trial coordinator will answer your questions and begin the screening process.

  1. Can you have CAR-T treatment if you have already had R-Chop Chemotherapy?

Answer from Dr. Koffman:  If your bone marrow function is adequate, you could have CAR-T after any chemo protocol.

  1. Is CAR-T cell therapy appropriate / effective for all CLL patients or does CAR-T not work on some forms of CLL?

Answer from Dr. Koffman:  We are still learning who does best with CAR-T therapy, but so far it does seem to work even for those with poor prognostic markers such as deletion 17p or mutated TP53 or unmutated IgVH, or those with a very heavy tumor burden.  Outcomes are probably worse in those whose CLL is uncontrolled and growing fast.

  1. What explains the almost 50% of patients that do not respond to CAR-T and how can the response rate be improved in the future?

Answer from Dr. Koffman:  The response rates vary from trial to trial and may be higher or lower than the 50% you quote.  The hope is that by improving the CAR-T cells themselves, treating patients earlier when their T cells that will be genetically re-engineered into the CAR-T cells are younger and healthier – and – adding other therapies to CAR-T that modify the immune response such as Ibrutinib, response rates will continue to improve.

  1. Has it ever been tried on untreated patients?

Answer from Dr. Koffman:  Nearly all new therapies are first tried on patients who have failed other options, and that is the case with CAR-T.  That may change over time.

  1. What are the side effects of treatment?

Answer from Dr. Koffman:  The most serious short-term side effects are cytokine release syndrome (CRS) and neurological events.  This can be very frightening and difficult, but the vast majority of patients have a complete recovery with no residual problems.  Long-term, some patients have persistent low levels on immunoglobulins that may need to be replaced.

  1. Is Ibrutinib’s effect on CAR-T therapy related to BTK activity or some other off-target activity?

Answer from Dr. Koffman:  We don’t know for certain, but the research suggests Ibrutinib’s off target effects on T cells may be why it can be beneficial.

  1. If you have had a BMT (bone marrow transplant) that hasn’t worked, is CAR-T an option following a BMT?

Answer from Dr. Koffman:  Yes, and I am living proof.

  1. Why not a W&W patient?

Answer from Dr. Koffman:  Some watch and wait patients may never need treatment, so why take any risks.  Plus, no treatment has yet been shown to improve overall survival if taken before therapy is needed for CLL.

  1. What is the difference between CAR-T and CAR-NK?

Answer from Dr. Koffman:  CAR-T cells use T cells and CAR-NK use a different lymphocyte, a NK or natural killer cells.  There are less data on CAR-NK.

  1. Can CAR-T be used for SLL just like CLL?

Answer from Dr. Koffman:  If treatment is needed, CAR-T should work well in SLL.

  1. What is the cost of getting CAR-T?

Answer from Dr. Koffman:  As of December 2020, CAR-T is only available for CLL patients in clinical trials.  Most insurance cover the “usual and customary” costs related to clinical trials and not covered by the trial, but it is always important to check with your insurance before moving ahead.  For the approved products in other blood cancers, insurance coverage is generally quite good.  The cash cost with no insurance of CAR-T and its related outpatient and hospital costs would be $100,000s or more.  There may be help available through charities and the manufacturer to help with the cost.

  1. If a CLL patient had Ibrutinib therapy that relapsed, would the CAR-T combination with Ibrutinib still be an option?

Answer from Dr. Koffman:  Yes, because it is probably Ibrutinib’s effect on the T cells that matters most, not its effect on the CLL.

  1. What about the possibility of directing the CAR-T to an antigen on the CLL cell, but is not present on the normal B-Cell?

Answer from Dr. Koffman:  Research is looking at other targets besides CD19 such as ROR1 that is not found on normal B cells.  There are much less data from these trials.

  1. What chemo is used with CAR-T?

Answer from Dr. Koffman:  Trials differ but FC (fludarabine and cyclophosphamide) are most commonly used before infusion of the CAR-T cells.

  1. Is there an age limit for treatment with CAR-T?

Answer from Dr. Koffman:  Most doctors would say it depends more on your “biological” age than your chronological age.  If you are healthy in your 80s, you might be a better candidate than someone with obesity, diabetes, heart disease and on dialysis who is 30 years younger.  Staying fit helps all cancer therapies.

Dr. Brian Koffman, a well-known retired doctor, educator, and clinical professor turned patient has dedicated himself to teaching and helping the CLL community since his diagnosis in 2005. He serves as the Executive Vice President and Chief Medical Officer of the CLL Society Inc.

Originally published in The CLL Society Tribune CAR-T Special Edition.