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iwCLL 2019: Dr. David Maloney on Targeted Agents, Transplants, and CAR-T Therapy for Treating Chronic Lymphocytic Leukemia (CLL)

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The number of treatment options for chronic lymphocytic leukemia (CLL) has greatly expanded in the past decade. Previously, most patients would receive chemoimmunotherapy, maybe then, followed by some experimental agents (a.k.a novel agent). There was a high rate of failure and patients would quickly run out of options.

Now the effectiveness of targeted agents has markedly improved and they are being used earlier in the course of treatment.  Today, what is the role of other options such as transplants and chimeric antigen receptor T-cell (CAR-T) therapies?

At the International Workshop on CLL (iwCLL) 2019, our own Dr. Brian Koffman interviewed Dr. David Maloney, Medical Director of the Cellular Immunotherapy Program at Fred Hutchinson Cancer Research Center in Seattle, WA. They discussed the debate around using targeted agents vs. transplants vs. CAR-T therapy for the treatment of CLL.

Takeaways:

  • Targeted agents are improving and extending the length of remissions, but there is still room for alternative therapies in those that are refractory to those targeted agents.
  • So far, it seems the best chance for a curative therapy is going to be a cellular therapy rather than a novel agent.

Stem Cell Transplants

  • Stem cell transplants work in CLL patients with low disease burden at the time of transplant. A number of factors are required to be eligible as you would need a donor and must be fit.
  • With transplants, there are also a number of risks and some patients can die from non-CLL-related complications (treatment-related mortality or TRM). In some patients, less than half, a transplant can be curative.
  • Transplants can result in chronic graft versus host disease that can be mild or miserable.
  • Nowadays, transplants are usually not done unless the patient has already failed nearly all options.
  • The number of transplants for CLL being performed is, therefore, declining.
  • For more information on stem cell transplants, check out our interview with Dr. Lindsay Roeker.

CAR-T Therapy

  • There is increasing use of CAR-T therapy though it is still experimental in CLL at the time of this publication.
  • CAR-T involves taking cells from the patient and altering them to add a chimeric antigen receptor, which is specifically made for different types of cancer.
  • For CLL, CAR T-cells are made to express a receptor for CD19, a marker found on all B cells. This allows them to attach to cancer cells that express CD19 on their surface.
  • After their cells are harvested to make the CAR T-cells, patients receive a low dose of chemotherapy so they won’t reject the genetically altered CAR-T cells. Then the CAR-T cells are given back to the patient where they will hopefully expand, grow, and attack the cancer.
  • Thus far, Dr. Maloney is seeing good results in patients that are refractory to most novel agents and deep remission in a subset of patients. CAR-T therapy is currently in phase II trials in patients who have failed ibrutinib therapy.
  • CAR-T therapy can result in several well-recognized toxicities such as cytokine release syndrome (CRS) and neurological events, but these side effects can be easily managed and are usually short in duration. Almost everyone fully recovers.
  • Some patients are disease-free more than 10 years after receiving their CAR T cells.
  • For more information on CAR-T therapy, please check out our CAR-T Resource Library.

Conclusions:

CAR-T therapy is a proven game-changer in other blood cancers and is promising in CLL. It is still undergoing clinical trials and that is the only way it can be accessed as of today.

Researchers have to start testing any new therapy in end-stage patients who are without a lot of options.  Once they can demonstrate safety and activity, they may be able to start moving it up earlier in the course of the disease. The hope is that someday CAR-T therapy could be used earlier in patients with less disease burden. This would hopefully minimize some of the associated toxicities and improve the response rate.

Please enjoy this interview with Dr. Maloney from September 2019 at iwCLL in Edinburgh, Scotland.

Take care of yourself first.

Ann Liu, PhD

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