Chemo-free treatment with acalabrutinib can benefit CLL/SLL patients never treated before: a plain language summary of the ELEVATE-TN study

[AussieNeil]

The ELEVATE-TN international study commenced in September 2015. The plain language article illustrates how this clinical trial was established and run to determine whether targeted therapy arms using acalabrutinib, a Bruton's Tyrosine Kinase inhibitor ( BTKi), with or without obinutuzumab, would outperform a chemoimmunotherapy arm using chlorambucil and obinutuzumab. The first draft of the plain language summary draft was submitted by Jeff Sharman & Shweta Hakre on 14 May 2024. It was accepted for publication on 16 January 2025.

Chlorambucil (Leukeran) is a very old chemotherapy drug, dating back to the 1950s. Obinutuzumab (Gazyva) is a more recent second generation humanised anti-CD20 monoclonal antibody targeted immunotherapy drug, which was developed in the early 2000s. It has proven slightly superior to the first generation anti-CD20 monoclonal antibody rituximab (Rituxan, Mabthera), which was developed in the 1980s and approved for human use in 1997. Rituximab is chimeric mouse/human antibody that is produced in mammalian cell culture using Chinese hamster ovary cells. Acalabrutinb (Calquence) is a second generation BTKi targeted therapy. It was approved for medical use in the United States in 2017 and in the European Union in November 2020.

Patients were divided into 3 groups:

1) acalabrutinib alone

2) acalabrutinib plus obinutuzumab, a monoclonal antibody

3) the usual chemoimmunotherapy treatment (chlorambucil plus a monoclonal antibody). Chemoimmunotherapy uses two or more treatments that combine chemotherapy and immunotherapy.

What are the key takeaways?

This study looked at how well treatment with acalabrutinib plus obinutuzumab (a monoclonal antibody) worked by measuring the length of time during treatment that a patient lives with the disease without it getting worse.The doctors estimated that 87% of patients who had acalabrutinib plus obinutuzumab would be alive without disease getting worse 4 years after starting treatment compared with only 25% of patients who had the usual chemoimmunotherapy option of obinutuzumab plus chlorambucil. It also showed that 96% of patients in the two groups taking acalabrutinib had their cancer stay the same or decrease compared with 83% of those treated with the usual chemoimmunotherapy.

The doctors found that the most common side effects (an unwanted and sometimes dangerous reaction caused by a medication) for the 2 groups of patients treated with acalabrutinib (with or without obinutuzumab) were diarrhea and headache, which happened more often during the first year of treatment and happened less over time.

What were the main conclusions reported by the researchers?

These results mean that acalabrutinib is a useful chemotherapy-free option and gave better results than chemoimmunotherapy with low side effects for patients with CLL/SLL who are starting their treatment for leukemia.

Full Text (PDF)

tandfonline.com/doi/epdf/10...

The original article, “Efficacy and safety in a 4-year follow-up of the ELEVATE-TN study comparing acalabrutinib with or without obinutuzumab versus obinutuzumab plus chlorambucil in treatment-naïve chronic lymphocytic leukemia”, is free to access at:

nature.com/articles/s41375-...

Neil

[Lil0ppie]

I’ve been on A since May. Did 6 cycles on O. My CLL is under control, and it’s a huge relief!

[spi3]

Thank you Neil for this exciting update!

[cajunjeff]

Interesting study. I am on acalabrutinib only. I have mostly mild side effects from it. I am so grateful to have a type of cancer that can be treated with a couple pills a day. It’s a miracle drug in my mind.

It is a pet peeve of mine, though, that when they do these clinical trials, they use chlorambucil as the comparative drug. Chlorambucil is a dinosaur chemo drug that has never been as effective as other chemo options for cll like bendustamine and rituxan or FCR. If you are doing a trial to compare the efficacy of the new cll drugs, make fcr the comparative therapy to make it a fair fight.

Did anyone, anywhere, even back when this trial was started, think chlorambucil would beat acalabrutinib? It feels like the drug companies stacked the deck on this trial to make certain their potential billion dollar baby drug won its first fight. Regardless , I agree with the results. Acalabrutinib is a better option than chemo for most all Cll patients.

[AussieNeil Partner Administrator in reply to cajunjeff]

Totally agree about chlorambucil being a poor choice, even though it was coupled with obinutuzumab. That's why I highlighted when the respective drugs were developed and approved. I remember several CLL research specialists being rather scathing about the choice of chlorambucil at the time the study was announced. The trial sponsors wanted to be absolutely certain that acalabrutinib would prove more effective than an approved treatment in that trial.

Neil