NO CD20? How concerned to be?

[anongirll1927]

Hi all! Went in with a recently diagnosed loved one to an oncology appointment recently. I don’t have FISH back yet, but I found out (at least preliminary) flow showed CD20 negative. Doctor Google sent me into a panic stating this was very not great news for NH lymphoma patients. But then it also said this was typical for CML patients (who usually seem to have a decent prognosis). But there’s pretty much nothing out there about this in CLL, I guess because it is so rare. Thankfully, my loved one has no signs of lymphoma and the docs seem to really think it is CLL (albeit possibly atypical), as everything else screams CLL. On top of all this, they are practically asymptomatic. I know some of the therapies target CD20, but are there some that don’t? How concerned should I be rn?

[AussieNeil Partner Administrator]

Confusingly, CD20 negative doesn't mean no CD20. It just means that the amount of CD20 expressed on the CLL cells is below a defined threshold. With flow cytometry testing. CLL has a characteristic immunophenotype expressing dim CD20, though it can sometimes be bright. A shorthand way of stating whether CLL CD20 expression is bright or dim is CD20+ (i.e. bright) or CD20- (i.e. dim).

The main anti-CD20 monoclonal antibody treatments used for CLL are rituximab (Rituxan or Mabthera), which has been successfully used for decades and the newer, slightly better obinutuzumab (Gazyva). Trials with ofatumumab weren't that successful.

Current commonly used CLL targeted therapies are either:

1) fixed term combination therapies, based on a BCL-2 inhibitor, (typically venetoclax/Venclexta) with either a BTKi; one of the 'brutinibs', or an anti-CD20 monoclonal antibody (rituximab or obinutuzumab).

2) Maintenance BTKi therapy.

Those with CLL expressing bright CD20 are in the minority, but even so, rituximab and obinutuzumab work extremely well with dim CD20 expression. Early anti-CD19 monoclonal antibody treatments didn't work as well. In the USA, rituximab infusions were even used for CLL maintenance therapy prior to the arrival of BTKi and BCL-2i targeted therapies. It was the addition of rituximab to fludarabine and cyclophosphamide back early this century, that led to the breakthrough first treatment (FCR) proven to extend survival time with CLL. (The FC is chemotherapy and the R immunotherapy, so FCR is chemoimmunotherapy.) The anti-CD20 antibodies lock onto the CD20 proteins on the CLL cell which both triggers CLL cell apoptosis and marks the CLL cell for destruction by our immune system - macrophages are attracted to the anti-CD20 antibody and gobble up the CLL cell.

Neil

[anongirll1927 in reply to AussieNeil]

Neil—thanks so much for your quick reply! The NP reviewing their paperwork (from Mayo Clinic, brought to Big Cancer Center) seemed to express that there was no CD20 expressing at all. She really didn’t know what to make of it.

That said, they are re-testing at Big Cancer Center. Hopefully it will come back as expressing, even if dim. However, even if they are still not expressing CD20, this post did give me a little hope about potential treatment options. I know it will limit treatment options, but I’m also trying to be hopeful that it isn’t the worst thing in the world!

Appreciate you!