Side Effects, Costs Can Be ‘Game Changers’ in Deciding MCL Treatment


With three BTK inhibitors approved for treatment of mantle cell lymphoma, patients and providers should consider side effects and insurance coverage before deciding on a drug.

Bruton tyrosine kinase (BTK) inhibitors have brought major changes to the mantle cell lymphoma (MCL) treatment landscape. However, not all patients benefit from these drugs, and cost and side effects are also apparent, leaving unanswered questions and the need for more research, explained Dr. Bijal Shah, associate member of the Department of Malignant Hematology at Moffitt Cancer Center.

“We all acknowledge that BTKs have unquestionably changed the treatment landscape for MCL. We now have a pill therapy that functions in many respects as well, if not better than, chemotherapy in the same space. The problem we run into is (that) there are still high-risk subsets that don't benefit from the BTKs. These are the same high-risk subsets that don't benefit from chemo either,” Shah said in a recent interview with OncLive, a sister publication of CURE®.

Those who may not benefit from BTK inhibitors include patients: with p53 mutations, whose disease is very proliferative, with Ki-67 more than 50%, and those with blastoid or pleomorphic morphology.

BTK Inhibitor Side Effects

Additionally, side effects must be considered – and closely monitored – when planning treatment with one of the three FDA-approved BTK inhibitors for MCL: Imbruvica (ibrutinib), Brukinsa (zanubrutinib) and Calquence (acalabrutinib).

Namely, cytopenias (when there is a lower-than-normal amount of blood cells) “have been the hardest thing to push through,” Shah explained, noting that these tend to be more common in patients receiving Imbruvica, in his experience.

With Calquence, a common side effect patients experience is myalgia (achy muscles) or headache, usually within the first month of treatment. This tends to happen a bit later for patients on Imbruvica.

“(The patient) is generally able to push through the headache, and Fioricet or something with caffeine seems to be an effective tool for managing the headaches,” Shah said.

Finally, patients who already have high blood pressure may want to talk with their care team about steering clear from Brukinsa.

“The number one thing that I've seen with zanubrutinib has been worsening of pre-existing hypertension, and it can be rather severe. I've had to admit a few patients to the ER for very high blood pressures, and incorporating things that I don't normally use, like clonidine, to help control some of the blood pressure fluctuations,” Shah said. “That has been, in terms of (side effects), one of the harder things, but something that we must keep in mind.”

Consider the Cost of Treatment

In addition to side effects, patients may need to consider cost and insurance coverage before being prescribed a BTK inhibitor to treat their MCL.

“I hate to say it, but insurance usually declares which (BTK inhibitor) we’re going to use before we make that decision. Certainly, we (have) found that sometimes one BTK is covered, and another is not,” Shah said.

Shah said that he recently treated a patient whose disease was progressing, so he wanted to switch to treatment with a BTK inhibitor. However, Calquence and Ibruvica had high co-pays that were too expensive. As disease continued to progress, Shah recommended treatment with Brukinsa, and even though it was the newest BTK inhibitor on the market for MCL, it was completely covered by insurance.

The patient’s expenses went from several hundreds of dollars every month to nothing. “That’s obviously a game-changer for the patient,” Shah said.

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