First results of a head-to-head trial of acala... - CLL Support

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First results of a head-to-head trial of acalabrutinib versus ibrutinib in previously treated chronic lymphocytic leukemia.

Jm954 profile image


Increased selectivity of the Bruton tyrosine kinase inhibitor (BTKi) acalabrutinib (Aca) vs ibrutinib (Ib) may improve tolerability. We conducted an open-label, randomized, noninferiority, phase 3 trial to compare Aca vs Ib in patients (pts) with chronic lymphocytic leukemia (CLL).


Previously treated CLL pts with del(17p) or del(11q) by central lab were randomized to receive oral Aca 100 mg BID or Ib 420 mg QD (stratified by del(17p) status, ECOG PS [2 vs ≤1], and number of prior therapies [1–3 vs ≥4]) until progression or unacceptable toxicity. Primary endpoint was progression-free survival (PFS) as assessed by IRC; secondary endpoints of all grade atrial fibrillation (AF), grade ≥3 infection, Richter transformation, and overall survival (OS) were assessed in hierarchical order.


533 pts (Aca, n=268; Ib, n=265) were randomized (median age 66 y; median 2 prior therapies; del(17p) 45.2%; del(11q) 64.2%). At a median follow-up of 40.9 mo (range 0.0–59.1), Aca was noninferior to Ib with a median PFS of 38.4 mo in both arms (HR 1.00; 95% CI 0.79–1.27). Aca was statistically superior to Ib in all-grade AF incidence (9.4% vs 16.0%; P=0.023). Among the other secondary endpoints, incidences of grade ≥3 infection (Aca: 30.8%, Ib: 30.0%) and Richter transformation (Aca: 3.8%, Ib: 4.9%) were comparable between arms. Median OS was not reached in either arm (HR 0.82 [95% CI 0.59–1.15]), with 63 (23.5%) deaths in the Aca arm and 73 (27.5%) in the Ib arm. Among any-grade AEs in ≥20% of pts in either arm, Aca was associated with a lower incidence of hypertension (9.4%, 23.2%), arthralgia (15.8%, 22.8%), and diarrhea (34.6%, 46.0%) but a higher incidence of headache (34.6%, 20.2%) and cough (28.9%, 21.3%). AEs led to treatment discontinuation in 14.7% of Aca- vs 21.3% of Ib-treated pts. Among any-grade events of clinical interest, cardiac, hypertension, and bleeding events were less frequent with Aca (Table).


In this first head-to-head trial of BTKis in CLL, Aca demonstrated non-inferior PFS with less cardiotoxicity and fewer discontinuations due to AEs vs Ib.

Clinical trial information: NCT02477696

There is a very good chart on the reference which I cannot upload for some reason. It's worth having a look at if trying to decide between Ibrutinib or Acalabrutinib.


15 Replies

Thanks Jackie so as far as longevity both deliver roughly the same and for us long-term ibrutinib users this in a way is reassuring and no need to threat that we are missing out on the second generation btk s which although deliver less early side effects the long-term outcome are the same

Jm954 profile image
Jm954Administrator in reply to cartwheels

Now that there are people who have been on Ibrutinib for more than a decade there may be some long term cardiac safety signals emerging with but the evidence isn’t conclusive yet. I would definitely change to Acalabrutinib if I got the chance.

cartwheels profile image
cartwheels in reply to Jm954

Well I only suffer mainly with acid reflux which I now take a one a day tablet for and high blood which again is under controlMy main moan about ibrutinib is lower back pain which has plagued me since I started but I just deal with it best I can think it's more coxis related now if I thought by switching drugs I could get rid of that then I definitely would

I discussed ibrutinib vs acalabrutinib with my doctor. The ibrutinib worked well for me, but I did have side effects - high blood pressure and diarrhea.

Knowing ibrutinib also can cause atrial fibrillation, I became concerned about the long term cardiotoxicity of ibrutinib. Could whatever about ibrutinib that raised my blood pressure be causing other cardio harm?

So I brought it up with my doc and he said there was no reason for me not to switch, he thinks acalabrutinib is a better drug.

I made the switch a few months ago. My blood pressure reduced to where it was before ibrutinib and my diarrhea went away. I have zero side effects with acalabrutinib that I can notice.

That does not mean that anyone who is doing well on ibrutinib should try to switch. We are all different. I am just sharing my experience with high blood pressure that I think ibrutinib was causing me. Ibrutinib was a life saver for me. I would not have switched but for the blood pressure issue.

Jm954 profile image
Jm954Administrator in reply to cajunjeff

Great to hear Jeff.

Rmjersey profile image
Rmjersey in reply to cajunjeff

Hi Jeff, I’m aged 61, TP53 and have been on Ibrutinib as a first line treatment for almost two years now. I too suffer from raised blood pressure and diarrhoea. For the blood pressure, 9 months ago my GP put me on Irbesartan 75mg - BP now averages 138/87. For the diarrhoea, my wife has banished me from the en-suite! Could I ask by how much your BP increased which prompted the switch to acalabrutinib? All the best,

cajunjeff profile image
cajunjeff in reply to Rmjersey

Jersey, my bp has always been borderline high, I would say about135/85. Ibrutinib pushed it up to 150/90 with some episodes up to 170.

My internist put me on bp meds which he continually had to raise.

I first discussed switching to acalabrutinib over concerns about my blood pressure. I eventually made the switch after a bad rash, although in retrospect I doubt ibrutinib caused my rash because the rash persisted when I paused ibrutinib. I was about to restart ibrutinib when my Cll doctor suggested I switch to acalabrutinib.

My BP now is about 120/70, but I am still on the meds. I am not sure where it would be off the meds, maybe back around 135. My internist said so long as the bp meds are not causing me side effects, I should stay on it. He prefers I be in the 120’s on my high number.

janvog profile image
janvog in reply to cajunjeff

Based on Mayo literature, with the approval of my hematologist, I started with CoQ10 and also unpasteurized organic apple cider vinegar, which lowered my BP by 5 to 10 points.

Doremefasol profile image
Doremefasol in reply to janvog

Are you sure, unpasteurized?

janvog profile image
janvog in reply to Doremefasol

Yes: Organic and not pasteurized, raw apple cider vinegar with "mother": The pasteurization would to inactivate the "good bacteria". The "mother" is a cluster in the liquid of bottle with a key concentration of beneficial bacteria. I definitely got the agreement and encouragement of my hematologist (Dr. Dr. two degrees) at a major cancer clinic network. His P.A. gives it to her husband for upset stomach: It seems to work counterintuitively to sooth the digestive system. I have not noticed any adverse reaction and instead a reduction of blood pressure by 5 t0 10 points. I started to take CoQ10 at the same time - thus I do not know whether one or both produced the reduction of blood pressure . The CoQ10 is recommended by Mayo Clinic for blood pressure and cardiovascular benefit. But I realize vinegar is an acid and flush mouth and throat with some water after ingesting food containing the vinegar: Two teaspoons twice daily mixed with puree of vegetable and salmon.

Yes Jackie, the chart was very useful. Wished the secondary cancer was less for A. Thanks lots!


Here is a summary article from MedPage Today that may help some understand the results of the ELEVATE-R/R trial:

Meeting Coverage - ASCO

Acalabrutinib Offers Less Wear and Tear on the Heart in CLL Patients - BTK inhibitor had less cardiotoxicity than ibrutinib, but similar efficacy

by Mike Bassett, Staff Writer, MedPage Today June 7, 2021

This from the article is key:

"Based on the data presented, acalabrutinib use will have an impact on patients' quality of life," Barrientos commented. "Although this was a high-risk cohort of patients with relapsed disease, this data confirms prior reports of tolerability of the drug, and would likely be extrapolated to non-risk patients and into earlier lines of therapy."

During a Q&A session, Byrd was asked how clinicians should decide which of these drugs to use.

"With the similar efficacy and diminished toxicity with acalabrutinib, that would likely be the first choice," said Byrd, adding that since they are different chemical structures, if a patient develops a rash "or some untoward event," ibrutinib could be considered. "And in younger patients there is less data with acalabrutinib, and using ibrutinib based on the ECOG study with rituximab may be a consideration, as well, based upon established data."

Having watched the continued progress on CLL treatment over the 14+ years since my diagnosis, the superior treatments keep right on coming. Better treatments = better QOL. The progress is really quite amazing.

Get Vaccinated & Be Safe / Stay Well - K9

Jm954 profile image
Jm954Administrator in reply to cujoe

Great information, thanks! :)

Hi Jackie - this is a crude and simple, but effective way to save the chart. Hit the "PrtSc" button on your keyboard, then open Windows Paint and simply "paste" the image. You can then cut it out or edit it as you see fit. Hope this helps you.

Jm954 profile image
Jm954Administrator in reply to Jungle-Jim

That's great, thanks! :)

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