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ASCO 2019: Dr. Koffman’s Pick #6: Acalabrutinib with Obinutuzumab for chronic lymphocytic leukemia (CLL)

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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.


Acalabrutinib with obinutuzumab (Ob) in treatment-naive (TN) and relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL): Three-year follow-up.

When this paper was presented by Dr. Jennifer Woyach and her team from Ohio State at ASCO in June, 2019, acalabrutinib had not yet been approved in CLL.

But on November 21, 2019 acalabrutinib was approved in both in treatment-naive (TN) and relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL).  Please see our official statement on this good news.

This abstract gives us some of the background on why this new BTK inhibitor will be joining ibrutinib as an important approved option at all stages of CLL therapy.


  • This trial studied acalabrutinib (Calquence), a selective BTK inhibitor that works in CLL in a similar way as does ibrutinib (Imbruvica) by blocking the B cell receptor downstream through inhibition of Bruton’s Tyrosine Kinase (BTK), used in combination with the potent anti-CD20 monoclonal antibody, obinutuzumab (Gazyva).
  • 19 TN and 26 R/R pts were treated.
  • Common adverse events (AEs) were
    • upper respiratory tract infection (71%) – this may have nothing to do with the drugs but must be reported.
    • increased weight (71%) – weight gain is increasingly being recognized as a risk with BTK inhibitors
    • maculopapular rash (67%) – this rarely requires the drug to be stopped
    • cough (64%)
    • diarrhea (62%)- often transient that resolved on its own
    • headache (56%)- a unique AE with acalabrutinib
    • nausea (53%),
    • arthralgia (51%)
    • dizziness (47%)
  • Serious AEs included the ¼ of patients who developed a low neutrophil count, a commonly recognized issue with obinutuzumab, the 2 who had bleeding issues and the 1 who had atrial fibrillation.
  • As expected, the overall response rate (OS) for the TN and R/R patients was very high, 95% and 92% respectively.
  • Even more impressive was the complete response rate (CR) of 32% in TN patients and 8% of the R/R group with 5 or 26% and 4 or 18% respectively reaching undetectable minimal residual disease (U-MRD) in the bone marrow.


This paper shows the deep responses and the good tolerability of this combination.

With the acalabrutib approval, we now have another strong option that, based on this abstract, can be logically combined with obinutuzumab for a deeper and hopefully more durable response.

CR and U-MRD are very rare in patients taking BTK inhibitors as monotherapy, reinforcing the value of using orthogonal (independent active) treatments in combinations.

A side issue: it is also worth noting that some patients who had no detectable CLL in their marrow (U-MRD) were classified as being in a partial remission (PR) as all their lymph nodes had not returned to normal size of <1.5 cm on imaging. This was my circumstance post CAR-T and can be due to scar tissue in the nodes preventing them from shrinking back to normal size, rather than there being persistent CLL in the lymphatic tissue.

Here is my ASCO video report:

Here is the link to abstract and the oral presentations: Acalabrutinib with obinutuzumab (Ob) in treatment-naive (TN) and relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL): Three-year follow-up.

Stay strong. We are all in this together.

Brian Koffman