Choosing a BTK Inhibitor for MCL: Consider Side Effects and Insurance Coverage

When choosing a Bruton tyrosine kinase (BTK) inhibitor for the treatment of mantle cell lymphoma (MCL), the decision often comes down to two considerations: insurance coverage and side effects.

“I hate to say it, but insurance usually declares which (drug) we’re going to use before we make that decision,” said Dr. Bijal Shah, associate member of the Department of Malignant Hematology at Moffitt Cancer Center. “Certainly, we’ve found that one BTK inhibitor is covered while another is not.”

BTK inhibitors all have the same basic means of operating: they bind to and block the BTK protein, an essential part of the B-cell receptor signaling pathway, which MCL uses for growth and survival. There are currently three BTK inhibitors approved for the treatment of MCL: Imbruvica (ibrutinib), Calquence (acalabrutinib) and Brukinsa (zanubrutinib).

Shah mentioned a patient he was treating who had copays of over $100 for the other two BTK inhibitors, but Brukinsa ended up not having a copay at all. “That’s obviously a game-changer for the patient.”

Besides insurance coverage, Shah said that he thinks about how the patient is going to do long-term when he is considering which treatment option to prescribe. He said that looking back on anecdotal data, about 30 to 40% of patients stop Imbruvica for side effects like atrial fibrillation and cytopenia, (low blood cell count) which Shah said has been “the hardest thing to push through.”

“It’s interesting that – in my experience, anyway – with (Imbruvica), we see a bit more in the way of that particular side effect,” Shah said.

With Calquence, patients may experience myalgia (muscle pain) or headaches within the first month of use.

“With headaches, you generally push through it… but myalgias are tougher. And you can see the same with (Imbruvica), but it tends to be a little later,” Shah said.

And while studies have suggested that Brukinsa has a higher rate of cytopenias, in his experience, Shah said that he has seen more instances of high blood pressure with this drug. Patients who already have hypertension may have it severely worsen with Brukinsa.

When making clinical decisions, doctors tend to look at these severe (grade 3) side effects, but patients and clinicians should have open communication about more minor maladies that come from the treatment. This may lead to changing of one BTK inhibitor to another, given that the disease is not getting worse.

“You have to keep in mind that for the year and a half or two and a half years – or whatever you get in terms of benefit with the drugs – if you have a chronic grade 1 or grade 2 toxicity, that’s not going to be a fun journey for the patient,” Shah said. “So with that background, what I would say is that if I’m seeing toxicity with one BTK inhibitor, I don’t hesitate to switch to another BTK inhibitor.”

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