Targeted Therapies

[Lil0ppie]

Could anyone provide - or point me in the direction of - an explanation for how targeted therapies are able to distinguish between cancerous and non-cancerous cells? This seems like a fundamental benefit of the new treatments.

Thanks.

[AussieNeil Partner Administrator]

It's not that targeted therapies can distinguish between cancerous and non-cancerous cells - at least so far. The advantage they have over older "chemo" treatments, is that they strongly target maturing B cells, leaving other body cells and mature B cells largely untouched. They do this by targeting proteins highly specific to B cells which can also be over expressed.

The older "chemo" treatments target cells undergoing fast cell division, such as along our digestive system, where they need to be frequently replaced through daily wear and tear. Hence the greater impact on bone marrow production and the occurrence of mouth ulcers and distressing GI issues which is more common with the older treatments.

Neil

[Lil0ppie in reply to AussieNeil]

Thanks. Does this mean that over time you’ll have fewer mature B cells?

[AussieNeil Partner Administrator in reply to Lil0ppie]

Yes, that's why it's common to see a drop in antibodies/immunoglobulins, as they are produced by mature B cells/plasma cells.Eventually healthy B cell production recommences after treatment, but it can take a while, up to a year after the last rituximab or obinutuzumab infusion. These monoclonal antibody treatments selectively target the CD20 protein cluster of differentiation almost exclusively found on maturing B cells.

Neil

[Lil0ppie]

Thanks. This is really informative. Presumably it will be a more long term issue for those of us on BTKi’s?

[AussieNeil Partner Administrator in reply to Lil0ppie]

As you have appreciated, with maintenance therapies, healthy B cell counts are also suppressed, though because they tend to have a lower expression of BTKi (or BCL-2) than CLL cells, sometimes people on maintenance therapy do somewhat respond to vaccinations.

Neil

[Lil0ppie]

Thanks again!

[Skyshark]

You have to weigh the targeted therapy that affects B-cells against the untargeted chemotherapy that came before.

Chemotherapy affects all dividing cells by disrupting the mitoses process. Then TP53 signals for cell death as the DNA copies are damaged. It didn't work for those with TP53 aberrations. It also affected all rapidly dividing cells, skin, gut lining, hair and nails.

Starting from approval of Ibrutinib in 2014 for CLL with TP53 aberrations and in 2016 for all types of CLL, the medical profession have been increasingly able to avoid using chemotherapy for CLL. The response of those with TP53 aberrations has also resulted in a fall in numbers that are referred for Allogenic SCT. But after 10 years of novel drugs there are now increasing numbers of patients that are refractory and progressed on all approved novel drugs. When new drugs under trial also fail the doctors are having to return to chemo and AlloSCT (mainly for TP53ab).

[Lil0ppie]

Thanks. Most helpful. Let’s hope that therapies in the pipeline fill that gap.

[Big_Dee]

Hello Lil0ppie

You have received great feedback on targeted therapies and explanation as to why some people on harsher chemo therapies loss all or most of their hair.