Acalabrutinib and Obinutuzumab for Frontline CLL Treatment

[Edalv]

Acalabrutinib plus obinutuzumab had a 100 percent response rate at 14 months and a deep reduction of disease in the bone marrow in treatment-naive CLL. Limited-duration combination therapies are starting to reshape how chronic lymphocytic leukemia (CLL) will be treated, but which combination is best is still unclear.

cllsociety.org/2024/12/acal...

[LeoPa]

Only 1 uMRD 😔

[Edalv in reply to LeoPa]

It depends how you look at it... If you are looking for a cure, this trial is not for you. The way I look at it it's another step in the right direction...

[Se_re_n_geti in reply to LeoPa]

6 % MRD. After 6 months infusion with O and 2x1, 100 mg A.

[Skyshark]

24 months Acalabrutinib with 6 doses of Obinutuzumab is probably cost comparable to Venetoclax + Ibrutinib, 15 cycles Ibr, 12 cycles Ven. If 6 more doses of Obin are used then it's more costly. It's a lot more costly than Venetoclax + Obinutuzumab, 8 doses Obin, 11 cycles Ven.

Typically 50% have Complete Response on V+O and V+I.

uMRD4 is reached by about 80% on V+O and 55% on V+I, this doesn't produce a difference in Progression Free survival (PFS).

CF A+O 25% and 5%.

How this relates to PFS is muddied by the 2 year duration of A+O, it's hoped that no one fails during a short duration treatment. The Ven+X short duration treatments have similar ~95% PFS at 24 months but that's 13 (V+O) and 10 (V+I) months after end of treatment.

For those that can't have Venetoclax it maybe better than continuous A with or without Obin as the time to becoming refractory or intolerant may be extended by repeated short duration treatments, as one supposes these times are related to time exposed to the drug (different for each individual).

I'd be most unhappy ending treatment with a partial response. Those on cBTKi that have a successful drug holiday are generally doing well, while others have an accelerated relapse with enlarged lymph nodes within weeks of discontinuing cBTKi drugs.

[stevesmith1964]

Hi I had Obinituzumab and Ibrutinib at diagnosis... stage 4, 4 yrs ago. I was in umrd within 240 days. I am on Acalabeutinib since and my monthly bloods are stable..

[Skyshark in reply to stevesmith1964]

Everyone is different. ELEVATE TN was 8 doses of Obinutuzumab and continuous Acalabrutinib. The Complete Response rate 26% at 24 months is similar to Short Duration A+O with possibly some on the SD A+O having had 12 doses of Obin. At 36 months the uMRD4 was higher in ELEVATE TN 11.7% (38% of the 31% that had CR/CRi).

Other reports have found the median progression free survival after stopping cBTKi drugs is 2 years.

A+O response is good but uMRD4 takes time

[Edalv in reply to stevesmith1964]

I am glad to hear your blood numbers are stable… Thanks for sharing your experience…

[stevesmith1964 in reply to Edalv]

I also lead a full pre covid pre cll life style.... do everything and go anywhere I did before.

[13SA21]

Hello, I have had the lymph node form of CLL since 2018.

In 2021 everything accelerated and my condition deteriorated sharply (tepscan revealing generalized lymph node invasion, fever yielding to nothing, exhaustion...). My hematologist started a Richter transformation test. An extremely negative emotional situation. Fortunately, it was “only” my CLL that was getting out of control.

I had a first-line treatment in 2021 of obinutuzumab (only for a month, as my blood count was back to normal) with the combination of acalabrutinib. My numerous adenopathies disappeared very quickly.

I stayed on the full dose of Acala for 2 years, then the half dose since.

At the beginning of 2024, my haematologist tried to put me off Acalabrutinib, but my lymph nodes took a week to reappear. Immediate resumption of treatment and immediate disappearance of the lymph nodes.

Result: the anguish of knowing that the LLc is still lurking and ready to reappear, but happy to have the chance to have access to this treatment which works so well for me (no side effects) and a perfect blood test.

[Edalv]

I am glad to hear the CLL is back under control. 🙏