EHA 2019: Dr. Paolo Ghia MD PhD on Phase 3 Trial for Relapsed or Refractory CLL (chronic lymphocytic leukemia)

At EHA (European Hematology Association) Annual Congress, 2019 in Amsterdam, I spoke with Dr. Paolo Ghia who is president of ERIC and conducts important CLL research out of  Milano, Italy.

Dr. Ghia discussed a Phase 3 trial of acalabrutinib, a second generation BTK inhibitor similar to ibrutinib, but that may have a different and perhaps better tolerated side effect profile.

Takeaways:

• This international ASCEND trial was open to all relapsed and refractory (R/) CLL patients as it compared acalabrutinib monotherapy to the treating doctor’s choice of either Bendamustine-Rituximab (BR) or idelalisib and rituximab (idR).
• As a phase 3 trial, it was designed to lead to the approval of acalabrutinib in R/R CLL.
• Acalabrutinib is an oral medicine taken twice daily.
• At the end of 16 months, acalabrutinib significantly improved progression free survival (PFS) compared to BR or idR, resulting in a 69% lower risk of progression or death.
• PFS rates at 12 mo were 88% with acalabrutinib and 68% with IdR/BR.
• Common side effects with acalabrutinib were headache (22%), neutropenia (low neutrophils) (19%), diarrhea (18%), anemia (15%) and cough (15%).
• Atrial fibrillation was seen in 5.2% of pts on acalabrutinib vs 3.3% on IdR/BR), bleeding in 26% vs 7.2%, but there were fewer major bleeds.
• Below is a graph of the PFS in the trial. You want the curve to stay close to the top which means nearly a 100% of patients are alive and not progressing. At nearly 2 years out, ∼80% on acalabrutinib had not progressed compared to only ∼1 of 4 at 20 months in the control arm.

Conclusions:

Acalabrutinib should be approved soon for R/R CLL based on these and other results as it is proven to be very effective and has a most manageable side effect profile. Differences compared to ibrutinib are more headaches (often controlled with coffee or acetaminophen) and encouragingly, less cardiac issues. It is also taken twice a day, compared to daily for ibrutinib.

We also discussed that this and other trials continue to prove that there is really no role for chemotherapy in treating R/R chronic lymphocytic leukemia.

And finally, we both agreed that any patient’s first move in treating CLL can have a domino effect, and so it must be carefully chosen, highlighting the critical importance of having a CLL expert leading the team.

Here is my EHA interview with Dr. Ghia:

Here is link to the EHA abstract itself and a video of the live presentation: An open-label Phase 3 study (CL-309; ASCEND; NCT02970318), the efficacy and safety of acalabrutinib monotherapy was evaluated vs investigator choice of IdR or BR in R/R CLL.

Thanks for reading and listening.

Stay strong. We are all in this together.

Brian