Dr. Paolo Ghia was the lead author on the first study of its type, comparing one novel therapy to another novel therapy or to standard chemoimmunotherapy (CIT) in chronic lymphocytic leukemia. The two novel therapies were acalabrutinib and idelalisib plus rituximab, and the chemoimmunotherapy option was bendamustine/rituximab (BR). All prior research had only compared a novel therapy to standard chemoimmunotherapy or immunotherapy.
The final analyses of the ASCEND trial after nearly two years of follow-up was presented at the virtual American Society of Hematology 62nd Annual Convention and Exposition or (ASH 2020)
In this interview, Dr. Ghia explains why this research was important and what was found.
- 310 relapsed/refractory (R/R) CLL patients were studied.
- This was a difficult group to treat. At least 75% had unmutated IGHV, 16% had del(17p), 27% had del(11q) and 42% were Rai stage 3/4 with more advanced disease.
- Patients were randomized to receive either acalabrutinib, a novel BTK inhibitor, or the investigator’s choice of bendamustine and rituximab (BR), a standard CIT, or idelalisib plus rituximab, a novel PI3K inhibitor and a monoclonal antibody.
- Not surprisingly, three out of four chose the idelalisib/rituximab (non-chemo) regimen.
- The study results confirmed the efficacy of acalabrutinib monotherapy in terms of progression free survival (PFS) which was not yet reached.
- In those treated with either idelalisib/rituximab or bendamustine/rituximab, the median PFS was 16.8 months.
- After 18 months of acalabrutinib, 82% were free from progression, compared to less than 50% in those who were treated with idelalisib/rituximab.
- Idelalisib/rituximab was much more effective compared to bendamustine/rituximab.
- Acalabrutinib had the better safety and adverse event profile. The most common side effect of acalabrutinib was headache, which occurred almost immediately after the first pills were taken, and typically lasted only 2-3 weeks.
- As expected with any chemotherapy, bendamustine/rituximab (BR) resulted in more hematological toxicity with low blood counts.
- Idelalisib plus rituximab provoked the usual well described adverse events seen with PI3K inhibitors including increased liver enzymes, increased incidence of infections, colitis, and skin rashes. These adverse events were reasons given by patients for discontinuing this therapy after 12-18 months
This trial was impressive because it was the first to look at the results when comparing two novel agents, although there are now several ongoing trials including one with acalabrutinib versus ibrutinib, where we have a recent press release but no peer reviewed materials yet. We discuss those finding in this overview: CALQUENCE met primary efficacy endpoint in head-to-head trial against ibrutinib in chronic lymphocytic leukemia (CLL).
BTK inhibitors such as acalabrutinib and ibrutinib have revolutionized the management of CLL. The two approved PI3K inhibitors, idelalisib and duvelisib block the same B-cell receptor as do the BTK inhibitors, but due to more difficulties with tolerance and side effects have been less used and are less effective than the BTK inhibitors. Still, idelalisib/rituximab proved to more effective compared to bendamustine/rituximab in this trial though less effective than acalabrutinib, largely due to patients needing to stop due to intolerance.
It seems fair to question what, if any, is the role of CIT for R/R CLL?
There is clearly no place for BR in the patients with del (17p) and unmutated IGHV. Hopefully this will be one of the last trials using CIT as a comparator in R/R chronic lymphocytic leukemia and all future trials will be compare novel agents and combinations.
Having more agents available for physicians to choose from to treat CLL is a good thing, because it allows physicians to tailor the medication regimen to the individual patient’s needs, preferences, and tolerances.
Visit https://ash.confex.com/ash/2020/webprogram/Paper134708.html to read the actual ASH abstract on the ASCEND trial and study all the details.
Watch Dr. Koffman, our Chief Medical Officer and EVP, in California, interview Dr. Paolo Ghia in Italy concerning his research presented at ASH 2020:
Thank you for reading this summary and watching this interview.
Robyn Brumble, RN
Director Scientific Affairs, CLL Society