What to Consider When Deciding CLL Treatment

  • Continued advancements in treatment for chronic lymphocytic leukemia (CLL) have given physicians more treatment options, particularly regarding BTK inhibitors and CAR T-cell therapy.
  • BTK inhibitors and CAR T-cell therapy lisocabtagene maraleucel (liso-cel), an anti-CD19 CAR T-cell therapy, are used to treat adult CLL patients with relapsed or refractory large B-cell lymphoma after two or more prior lines of therapy.
  • Dr. Adam Kittai, an Associate Professor of Medicine at Mount Sinai in New York, explains that BTK inhibitors such as pure ibrutinib are easier on the patient partly because they can be taken orally and take less time to obtain, thus making it his first treatment option.
  • Dr. Kittai says that CAR T-cell therapy, “We only give it one time, and it requires specialized care” at a facility familiar with it. He adds that it also comes with “significant toxicity” and can take roughly two weeks to manufacture.
  • Sometimes, a BTK inhibitor may be prescribed in the interim, while CAR T-cell therapy is manufactured to help stabilize the patient.

You now have more options for treating your chronic lymphocytic leukemia (CLL) patients, thanks to the continued progress of Bruton’s tyrosine kinase (BTK) inhibitors and the recent approval of chimeric antigen receptor CAR T-cell therapy. Lisocabtagene maraleucel (liso-cel) – anti-CD19 CAR-T cell therapy helps treat adult CLL patients with relapsed or refractory large B‐cell lymphoma (LBCL) after two or more lines of systemic therapy. The big question for physicians is sequencing of these medicines and deciding which patients will benefit.

Ibrutinib (brand name: Imbruvica), a type of BTK inhibitor, helped revolutionize CLL treatment as a “chemotherapy-free” front-line treatment option following its FDA approval in 2016.

Dr. Adam Kittai, an Associate Professor of Medicine at Mount Sinai in New York, explains to SurvivorNet that both of these drugs were approved after patients had received two prior lines of therapy—a prior BTK inhibitor and Venetoclax (Venclyxto), a BCL2 inhibitor that helps slow cancer progression.

“Now the question becomes, which drug do I reach for first? Do I reach for the pure ibrutinib first in this space, or do I reach for CAR T-cell therapy? I think for the majority of patients, I’m likely to reach for the pure ibrutinib,” Dr. Kittai said.

He adds that ibrutinib, like other BRK inhibitors, can be taken orally, making it easier for the patient.

The Ease of BTK Inhibitors May Give It the Edge

Dr. Kittai prefers ibrutinib over CAR T-cell therapy because the BTK inhibitor was designed to work in patients who’ve “progressed on the covalent BTK inhibitors.”

“When you have a patient who has already gone through our major classes of drugs, typically older may have a lot of disease that’s flaring, the pure ibrutinib is off the shelf,” Dr. Kittai said.

“CAR T-cell therapy, we only give one time, so it requires specialized care. So, you need to have a center that’s familiar with giving the CAR T-cell therapy. It does come with significant toxicity with the cytokine release syndrome as well as the [immune effector cell-associated neurotoxicity syndrome] (ICANS), the neurotoxicity, and you also have to wait,” Dr. Kittai further explained.

CAR T-cell therapy’s effectiveness depends on cell manufacturing, a multi-step process that can consume precious time. Research published in the Journal of Experimental Medicine notes that “the overall process involves isolation of the starting cell population from the leukapheresis product, T-cell activation, genetic modification, ex vivo expansion, final product formulation, and product release testing.”

The manufacturing process can take roughly two weeks to complete.

“We still have that issue of manufacturing time where from the time of apheresis to create the CAR T product to receiving the CAR T itself, patients need to receive something in the interim to ensure their disease is stabilized. So, I think, for the most part, I’ll pick pure ibrutinib first or at least use it as an agent to stabilize the patient prior to CAR T-cell therapy,” Dr. Kittai explained.

Ongoing advancements in CLL treatment continue to offer much-needed hope for patients who have already progressed or cannot tolerate primary therapies in the BTK inhibitors and venetoclax.