Acalabrutinib Plus Obinutuzumab Prolongs Progression Free Survival Compared to Other Targeted Agents in Chronic Lymphocytic Leukaemia (CLL)

[AussieNeil]

First-line acalabrutinib plus obinutuzumab prolongs progression-free survival (PFS) compared to ibrutinib-obinutuzumab and venetoclax-obinutuzumab for patients with chronic lymphocytic leukemia (CLL), according to a study published in Clinical Lymphoma, Myeloma, & Leukemia (2020 Oct 29;S2152-2650(20)30579-6).

“Available targeted agents for the upfront therapy of chronic lymphocytic leukemia (ie, ibrutinib, acalabrutinib, venetoclax) have rarely been compared in head-to-head clinical trials,” explained Stefano Molic, MD, Azienda Ospedaliera Pugliese-Ciaccio, Italy, and colleagues, who performed this literature review and meta-analysis.

The base-case network analysis included 3 trials: ILLUMINATE, ELEVATE-TN, and CLL14.

Dr Molic and colleagues reported that across the targeted agents, no differences in the frequency of adverse events were observed.

“This systematic review and network meta-analysis indicated that upfront AO [acalabrutinib-obinutuzumab] prolongs PFS in comparison with IO [ibrutinib-obinutuzumab] and VO [venetoclax-obinutuzumab], whereas no differences are observed between IO, VO, and single-agent A,” Dr Molic and colleagues concluded.

journalofclinicalpathways.c...

The summary article goes into a bit more detail on the Relative Risks and Confidence Intervals for the various combinations examined, then the authors conclude “Hopefully, ongoing studies will further delineate the position of different TAs (targeted agents) in chronic lymphocytic leukemia therapy based on effectiveness, availability, safety, cost, and treatment objectives," To me, that indicates that these are all promising drugs/combinations and we really won't know which combinations provide the longest remissions until we see how these new, 'non-chemo' approaches perform over a longer period of time and with more patient results. Without head-head comparisons, it's also difficult to perform accurate comparisons.

This is an unlocked/open post, so it can be found by non-members: healthunlocked.com/cllsuppo...

Neil

[DRM18]

In such circumstances, is Acalabrutinib taken indefinitely or for a fixed duration? (Confession: I didn’t click on the links to read more.)

[MsChief in reply to DRM18]

Thank you Neil - helpful study - as a patient on low dose Ibrutinib I know at some point I will move on to another treatment. It is nice to know that new concepts are being trialed constantly.

[AussieNeil Administrator in reply to DRM18]

As I noted above, the best performing first line treatment combination was acalabrutinib plus obinutuzumab and "no differences are observed between IO, VO, and single-agent A"

There's not much more in the cover article for the paper from what I quoted.

Neil

[Justasheet1]

Neil,

What exactly are they saying here? Is there an advantage to acala/obini compared to ven/obina and ibr/obina? Or it equally efficacious?

Jeff

[AussieNeil Administrator in reply to Justasheet1]

The Relative Risk indicated that acalabrutinib plus obinutuzumab demonstrated improved PFS, but the Confidence Intervals are fairly wide and overlapping - meaning that longer observations from more patients will be needed to improve the confidence in the analysis. Ideally we want a big difference in Relative Risk along with non-overlapping Confidence Intervals to show a definitive difference in the effectiveness of the compared treatments.

Neil

[Justasheet1 in reply to AussieNeil]

So they were not actually comparing them head to head in a stand alone trial but comparing data from 3 preexisting trials. Sounds like they’re all good choices!

Thanks Neil

[Smakwater in reply to AussieNeil]

Much to Ponder Neil,

Linear observations in real time, yet non linear and exponential over time and far beyond a quadratic view.

The constraint is that we as humans do not live long enough to see the entirety of the matrices solved.

I will have glass of each, and a double of the better.

JM

[Pageboy]

AO is my treatment plan so good to read such positive news. Different combinations are being tested all the time so it is all encouraging. Thanks for posting.

[Eagles1]

Neil,

Can MRD - be achieved through A&O? And what is the duration of this treatment?

Thanks,

Lee

[AussieNeil Administrator in reply to Eagles1]

uMRD (new term for MRD-) can most certainly be obtained with A&O. The combination treatment is typically 14 x 28 day cycles of A, with 9 infusions of O over a 6 x 28 day cycle period early on. Total treatment period is about 13 months.

[Eagles1 in reply to AussieNeil]

Your knowledge and insight is great. As I'm not retired yet, do any of these treatments prohibit me from continuing to work? Thank you!

[AussieNeil Administrator in reply to Eagles1]

How we respond to treatment is very individual and unfortunately there is no way to predict how someone will respond to a given treatment. Some are able to continue working (with time off for hospital visits for anti-CD20 Obinutuzumab infusions and possibly the Venetoclax ramp up) if relevant. Others may struggle with gastrointestinal side effects, headaches, fatigue, infections or other side effects that make it very challenging to keep working, or at least keep working full time. The side effects do tend to reduce over time.

Neil

[Pinhead1 in reply to Eagles1]

My husband finished one of these trials two months ago. When it was finished, they took him off of all medications. He was on the trial that only required 4 infusions of Obinutuzumab. He was able to continue to work. But due to the pandemic, he decided to retire early. We moved back to California so now we have 2 hospitals watching him. (Swedish and Moore Cancer Center.)

[Eagles1 in reply to Pinhead1]

Thank you for that information. I know everyone has different situations but did your husband have any side effects from either treatment?

[Pinhead1 in reply to Eagles1]

On his third infusion of Obinutuzumab he had a low white blood cell count. They gave him 2 shots to raise it and he was fine.

[Eagles1]

Thank you! My local hematologist thinks I’ll need treatment within a year. I’ll be seeing a specialist in Boston in February for a second opinion. I trying to evaluate my opinions, however he’ll have to help me decide. Happy new year.

[Hidden]

Thank you and Happy New Year, Neil!!

[VidaPlaya]

Thank you, Neil, for this post! My husband just finished his 5th cycle of O, and last month his flow cytometry showed "no abnormalities detected" - he had 20% abnormal lymphocytes before starting treatment. He'll still get a bone marrow biopsy whenever "elective" surgeries can be scheduled in 2-3 months, but he's gotten so much of his life back and the treatment went far smoother than I feared. (He'll says actually miss his post-infusion steroid high, though, haha) One thing we wondered about was whether he'd have to stay on A forever, so I'm going to read up on the link you posted and talk to the oncologist when he goes for his last infusion end of month.

[AussieNeil Administrator in reply to VidaPlaya]

Treatment protocols are still evolving, based on experience gained. How long the oral drugs are continued may also be influenced by the depth of response achieved. With A+O, your husband may be required to stay on Acalabrutinib indefinitely, so it's a good question for his oncologist.

Neil