Optimizing Treatment of Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

[Jm954]

This is a short paper setting out the non trial option for patients needing treatment after a targeted therapy

jnccn.org/view/journals/jnc...

Jackie

[cllady01 Former Volunteer]

Thank you, Jackie. That is a very readable and relatable read.

I hope you are doing well.

[johnliston]

Jackie, I did I/V the first time around and I don't see any reason it shouldn't work the second time. The time limited treatment and combination should inhibit the development of mutations and I haven't seen and data on clonal selection. So someone will have to tell me why it shouldn't work the second time or even the third time.

Except maybe cost.

john

[Jm954 Administrator in reply to johnliston]

I agree

[alpek in reply to Jm954]

There was an update posted on the captivate trial linked below that discussed Ibrutinib re-treatment response.

"As of April 2022, a total of 12 patients who experienced disease progression following fixed-duration ibrutinib plus venetoclax were retreated with ibrutinib monotherapy. The duration of single-agent ibrutinib retreatment in these patients ranged from 6 months to 32 months. Of the 11 patients determined to response evaluable, 9 were found to have a PR to retreatment, 1 had a PR-L, and 1 achieved stable disease."

onclive.com/view/updated-ca...

[annmcgowan]

Thank you Jackie very interesting. Can I ask if this applies to the U.K.? If so are these options open to all of us on the NHS now?

I remain on the Flair trial but will stop in around 18 months. Hope to be part of the static trial but don’t know if it is set up locally yet.

I hope your own health is going well.

Ann

[Jm954 Administrator in reply to annmcgowan]

They are available in England, Scotland and Wales Ann.

STATIC seems to be endlessly delayed

[annmcgowan in reply to Jm954]

Thank you Jackie. Take care

Ann

[CLLerinOz Administrator]

Thanks, Jackie, What a great summary article. I really liked the easy to follow chart, too.

Follow up treatment choices after targeted therapy for CLL

[LeoPa]

Isn't Pirtobrutinib a pi3k inhibitor? Isn't that the same as a non covalent BTK inhibitor? I think I'm lost here 🙂

[MrMidnight in reply to LeoPa]

As I understand it, Pirtobrutinib (Loxo-305) is a noncovalent BTK inhibitor. Idealalisib is a pi3k inhibitor.

[LeoPa in reply to MrMidnight]

Thanks!

[Justasheet1]

BTK and PI3K are different pathways for signaling in the B cell.

Pirtobrutinib is more akin to ibrutinib; hence the name.

[LeoPa in reply to Justasheet1]

Thanks!

[Smakwater]

Thanks for the read Jackie,

In other data it appears that venetaclax is still weighing well across all measures for front line. From this article it seem to be second to the covalent BTK's for progressive disease/recurrent CLL when venetoclax was the frontline treatment (84% to 72.2% OS). I learned yesterday that it is acceptable for venetaclax to be used as a monotherapy in relapse wherein the probability of TLS is low. What I mean is that if one is treated before the tumor burden progresses, there is no need to be pre treated with obinutuzumab. This would then not be an option for those with high WBC and no other symptoms, rather it would be used for patients with low counts and specific severe symptoms including night sweats, and fatigue.

It sounds to me like there is a building consensus that Ibrutinib is becoming a favorable way to pre treat for venetaclax whether front line or relapse. Although I am not yet swayed to believe that BTK's are better debulking agents than Obinutuzumab, We should all keep an eye on this, because although Obinutuzumab is a very efficacious CLL drug, it is known to deplete healthy B cells as well as the cancer cells.

My personal add is that I am now 44 months from beginning O+V and yesterday I received verification that my Flow Cytometry reveals no CLL. Although the term MRD negative was not expressed, I understood the result to be just that. All of my labs have been within range for the past two years with the exception of IgM being slightly low. My neutrophils have recovered, however, they also are trending on the lower end.

Given that I am unmutated IGHV, I am very pleased to share this result and to offer encouragement to anyone facing treatment.

My problems are now that I am living longer, I have to deal with the other ugly aging challenges.

Cheerio!

JM