Smart Patients Get Smart Care™

The World’s Leading Authority for Chronic Lymphocytic Leukemia Patients

ASCO 2019: Dr. Koffman’s Pick #3 Acalabrutinib in ibrutinib-intolerant relapsed/refractory chronic lymphocytic leukemia (CLL)

In science and medicine, information is constantly changing and may become out-of-date as new data emerge. All articles and interviews are informational only, should never be considered medical advice, and should never be acted on without review with your health care team.

Dr. Brian Koffman, the Executive Vice President (EVP) and Chief Medical Officer (CMO) of the CLL Society, counts down his top ten CLL related abstract from ASCO or the American Society of Clinical Oncology Annual Meeting held May 31 – June 4, 2019, Chicago, IL.


Phase 2 study of acalabrutinib in ibrutinib (IBR)-intolerant patients (pts) with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL)

The reason many patients stop ibrutinib is not that their CLL is progressing, but rather the side effects has become intolerable and then they stop their medication.

This is a particularly important problem with drugs such as ibrutinib where it is generally taken until disease progression or intolerance.

This multi-center study looked at 60 patients who had stopped ibrutinib because of intolerance AND whose CLL had progressed when they went off ibrutinib.


  • The average age was 70.
    • 1/3 had bulky (>5 cm) lymph nodes, del 17p was found in 28%, del 11q in 23% and unmutated IGHVin 79% – a tough group to treat.
  • The common adverse events that led to ibrutinib discontinuation were atrial fibrillation/flutter in a ¼ of the patients, followed by diarrhea in 12%, arthralgia (joint pain) in 10% and rash in 12%.
  • At a median follow-up of 19 months, 2/3 of patients remain on acalabrutinib.
  • Discontinuations of the acalabrutinib were due to progressive disease (13%) and adverse events (10%); pneumonia in 2 patients or diarrhea, headache, ascites (fluid in the abdomen), arthralgia (joint pain), subdural hematoma (intracranial bleeding), all in one patient.
  • Common side effects on acalabrutinib were diarrhea (48%), headache (40%), contusion (35%) and dizziness (32%). Atrial fibrillation occurred in 3 patients and major hemorrhage in 2.
  • 4 acalabrutinib patients died, thought it was not clear that the medication was the cause.


In this study presented at ASCO 2019, two out of three R/R chronic lymphocytic leukemia patients who were intolerant of ibrutinib were able to tolerate acalabrutinib for more than a year and half.

Keep in mind that it is prudent to assume that for any patients who progress on ibrutinib, acalabrutinib also will not work. It is, however, a good option for those who can’t handle side effects from ibrutinib.

Now that it is approved by the FDA for chronic lymphocytic leukemia, it will likely be used more broadly instead of ibrutinib rather than only in cases of ibrutinib intolerance. Will future patients intolerant of acalabrutinib when used first be offered to switch to ibrutinib?

It is good to have options.

Here is the link to my video review of the ASCO abstract:

To read the original abstract, click on: Phase 2 study of acalabrutinib in ibrutinib (IBR)-intolerant patients (pts) with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL)

Thanks for reading and watching.

Stay strong. Be tolerant, but not too tolerant.

We are all in this together