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Side Effects of Stopping Ibrutinib Treatment for CLL

Side Effects of Stopping Ibrutinib Treatment for CLL
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Published on November 4, 2020

What Happens When Ibrutinib (Imbruvica) Treatment for CLL is Paused?

Patients with chronic lymphocytic leukemia (CLL) on ibrutinib (Imbruvica) should think twice before stopping treatment — even if it’s just for a few days.

A study published last month in The Oncologist found that about 25 percent of patients with CLL experience a flare of disease after a temporary discontinuation of ibrutinib. Stopping treatment is a common strategy to deal with the drug’s potential side effects.

“Ibrutinib is a very effective treatment for chronic lymphocytic leukemia but needs to be taken continuously,” the study authors wrote. “Unfortunately, therapy with ibrutinib is associated with various side effects, including bleeding and hematologic and non-hematologic toxicities, as well as drug-drug interactions, that may necessitate dose modifications or interruption of treatment.”

How Long Do You Take Ibrutinib?

Ibrutinib, sold under the brand name Imbruvica, is a once-daily, oral Bruton's tyrosine kinase (BTK) inhibitor, initially approved in 2014. BTK inhibitors, which also include acalabrutinib (Calquence), and zanubrutinib (Brukinsa), work by shutting down the BTK enzyme, a crucial part of the B-cell receptor signaling pathway. Certain B-cell leukemias and lymphomas use B-cell receptor signaling for growth and survival.

Common side effects of Imbruvica include anemia, neutropenia (which may lead to low white blood cell count, increasing the risk of infection), diarrhea, swelling, nausea, upper respiratory issues and musculoskeletal pain. A 2018 study of 320 CLL patients treated with ibrutinib found that 21 percent discontinued therapy due to progressive disease and 32 percent because of intolerance.

CLL Progression in Patients Who Stop Ibrutinib Therapy

In the aforementioned study published in The Oncologist, investigators identified 372 patients with CLL who were treated at the Mayo Clinic in Rochester, Minnesota, between 2012 and 2019 and were prescribed ibrutinib. Among the cohort, 143 (38 percent) had at least one interruption in therapy with a median duration of eight days. Overall, the temporary disruption ranged from one to 59 days, and the number of interruptions, from one to seven. The most common reasons were periprocedural (treatment stopped around the same time as a medical procedure such as a biopsy), bleeding, neutropenia, and joint and muscle pain.

Of the 245 times that treatment was interrupted, a disease flare was observed following 41 of them (17 percent). Of the 143 patients who experienced an interruption, one-quarter of them (35) reported a disease flare, with most (21) experiencing mild flares involving fatigue, fever, painful lymph nodes, night sweats and body aches, headache, and abdominal pain. The remaining 14 patients experienced severe flares, which included new or worsening symptoms — fatigue, fever, night sweats, swollen and painful lymph nodes, nausea, labored breathing, an enlarged spleen, and high levels of lactate dehydrogenase (LDH), indicating some form of tissue damage.

While the disease flare did not impact patients’ survival or progression of their disease, in 34 percent of the treatment interruptions, it led to either acute hospitalization, prolongation of an ongoing hospitalization, or emergency department evaluation. In all cases, the flares resolved once the patient resumed their ibrutinib treatment. According to the authors, healthcare providers can manage flares by:Ibrutinib and Venetoclax

  • Resuming ibrutinib when able
  • Prescribing corticosteroids either before (as a preventative method) or after the disease flare
  • Limiting the number of days treatment is stopped
  • Suppressing proinflammatory cytokines, which can make the flare worse

And if a patient can’t tolerate ibrutinib at all? “If the patients have been on the drug for some time, they may have achieved quite a deep remission, and they may no longer meet criteria for needing therapy,” said Dr. Jennifer Brown of the Dana-Farber Cancer Institute in Boston at an education session at the 2018 American Society of Hematology (ASH) meeting, as reported by MedPage Today. “So, I will usually just observe them, let them recover from the side effects, and see what happens."

If their CLL progresses, other treatment options include venetoclax (Venclexta) with obinutuzumab (Gazyva) or rituximab (Rituxan), Dr. Brown told MedPage Today. One study found that with venetoclax after ibrutinib, among 91 patients whose last line of therapy was ibrutinib, 65 percent responded to treatment. However, single-agent ibrutinib demonstrated strong results after eight years of follow-up as a first or second-line treatment for patients with CLL. The overall response rate was 89 percent.

BTK Inhibitors are Effective in Treating CLL

“…I actually do believe that BTK inhibitors long term have better outcomes than the other oral agents,” said Dr. Richard Furman, a medical oncologist at Weill Cornell Medicine in New York City, in an interview with Patient Power Co-Founder Andrew Schorr. “And the truth is, we do have seven-year data for ibrutinib, which I do believe is equivalent to the other BTK inhibitors,” Dr. Furman said. “I speak to them all as a class, but I do think BTK inhibitors by and large are more efficacious. And so, they're often my first choice.”

~Megan Trusdell

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