Are there any targeted drugs that only kill cancerous wbc?

[PACWOMAN]

I have very high wbc,and will probably be given calquence which I thought only targeted cancerous cells, however, after talking to my consultant apparently this is not true. I don't understand why it is called a targeted drug if it kills healthy red and white blood cells, leaving you vulnerable to infection. I haven't had any infections despite everyone around me getting covid etc., so I'm reluctant to damage my health by taking a drug that might cause more harm than good. I also haven't had information about immunotherapy drugs,are they less harmful?

[AussieNeil Partner Administrator]

Targeted CLL therapies primarily target B cells that are in the maturing phase. T and NK cells, along with neutrophils, eosinophils, basophils and monocytes are not attacked. There are a few body cells that can be slightly affected too, but the later generation versions are generally more finely targeted. Older non-targeted treatments (chemo), were less discriminatory, which is why hair loss and mouth sores were common side effects. Non of the approved CLL drugs specifically target CLL cells, though they may be more targeted if the target is over expressed in CLL cells compared to healthy cells.

Red blood cells are not targeted by any of the targeted therapies. Their production, along with the production of other blood cells can be slightly impacted by bone marrow suppression. As the bone marrow infiltration is reduced by the CLL being targeted, more bone marrow capacity becomes available and other blood counts improve.

Immunotherapy drugs (anti-CD20 monoclonal antibodies) are also targeted to cells only expressing CD20, which is primarily maturing B cells. They have the disadvantage of remaining in circulation in the blood, killing off new B cells as they are released from the bone marrow. Without B cells, you can't make antibodies from vaccinations or infections.

Modern targeted therapies are generally well tolerated. Some of us don't even experience side effects. If you keep putting off treatment, bone marrow infiltration will eventually result in falling platelets, anaemia and falling white blood cell production, increasing the risk of bleeding, organ damage and infection respectively. Enlarging nodes and spleen can also eventually cause problems.

Neil

[PACWOMAN in reply to AussieNeil]

Thanks for your reply Neil, I'm understanding how they work better now, although it's still a bit confusing for me as I've never been ill in my life and don't have the symptoms of cll. I'll take your advice and try Calquence, hope I don't have any side effects x

[AussieNeil Partner Administrator in reply to PACWOMAN]

I've only explained how targeted therapies work, so that you can appreciate why Calquence is a good treatment recommendation and make an informed choice.

Neil

[kitchengardener2 in reply to AussieNeil]

Thank you Neil you have (as always) explained this in a way that I can understand. Does this mean therefore that however many times we are vaccinated against new viruses such as Covid19, we are unlikely to gain any benefit? I understand (I think) that our cells will remember what we had prior to treatment for CLL but won't take on anything new? So does this mean that treatment such as Evosheld will have limited success? Like so many CLL patients, I am still being extremely cautious about rejoining the world and being able to travel. At 70 and 71 my husband and myself really do want to be able to travel this winter (we most certainly wouldn't venture into airports etc during busy periods). It is for this reason that I was hoping that IF Evosheld was approved, then it might just give us a little more hope.

[AussieNeil Partner Administrator in reply to kitchengardener2]

Evosheld effectively replaces the antibodies you would have made if you didn't have CLL. Medical scientists isolated good antibodies from recovered patients, then slightly modified how they were made so that they would last longer. The concern with Evusheld is that it has reduced effectiveness against current variants, (hence the higher dose recommend). We also obviously have no idea how it will perform against the next variants coming along.

Your antibody response to vaccines and infections depends on your degree of immune compromise from your CLL and from current or recent treatment. Studies have shown that if you have some healthy B cells, you just take more boosters to get a response. The problem we are facing now, is that current vaccinations are for the original SARS-CoV-2 variant. New vaccines providing coverage for more recent variants will soon be available.

You probably get more T cell protection than from B cell (antibody) protection with CLL.

Neil

[kitchengardener2 in reply to AussieNeil]

Thank Neil, so because I am taking Acalabrutinib does that mean that my B cells wouldn't work, I have had five covid vaccinations and so far don't appear to have any antibodies for covid. I live in hope. Had my 3 monthly telephone consultation this morning and all seems well. Heamaglobin 127 and White Cells 12 she said Lymphocytes and Neutrophils were all good, she will send a print out.

You know I was concerned about the diagnosis of AFIB after my scalding accident. I have been trying without success to get a proper diagnosis without my being in shock. I was concerned that taking unnecessary medication wasn't good but my GP wasn't prepared to refer me to cardiology. My heamatologist (wonderful lady that she is) informed me that I have an ultra sound check booked for 19th August, it would have been good if I had been told! She has also requested a 24 hour monitoring tape and a cardiology referral. She is ok with my taking the Apixaban along with my Acalabrutinib but agrees that if it's not needed then no point in taking it. She will review after the cardiology appointment.

[AussieNeil Partner Administrator in reply to kitchengardener2]

Acalabrutinib inhibits B lymphocytes, so yes that's why it's hard for them to mature into plasma cells if they are inhibited.

Neil

[Pacificview in reply to AussieNeil]

Neil10 months later and your information is still being read and valued...thank you!

[Winegrape]

When I needed to start treatment last year, I asked about Venetoclax w/ immunotherapy because he only offered me the one you are scheduled to take. He said with my age, female 61, that it would be a good option. He said it can be harder when you're older, I'm not sure why. Maybe having to go through the immuno infusions? 9 of them, but they were easy and knowing after a year of the pills I might be in remission for 5+ years I'm happy I chose that option. I would ask your doctor about it.

[PACWOMAN in reply to Winegrape]

Thanks for your advice, sounds like the main drawback of immunotherapy is having to visit hospital which I hate, so I suppose the tablets are an easier option x

[skipro]

Great question

The new meds are far more target than the old things like the chemo I had

I just wrote up an article about a study in phase 1 moving to phase 2 clinical trial.

It’s posted on the CLL society web page

The study used off the shelf NK or killer cells created to target only the cancer cells

Unfortunately the cancer cells mutate so over time, new treatments have to be developed to attach to the new mutated cancer cell

Wish you the best

Skipro

[PACWOMAN in reply to skipro]

Thanks for your reply Skipro, it's seems a lifetime ago that I had to watch my best friend and my mother having cyanide dripped into their veins in an attempt to kill the cancer. It was a toss up whether it killed the cancer or the patient first, in their case it was unfortunately the patients. I am still suffering pts thinking about it, wanting so much to scream at them not to do it, so I'm very suspicious about any treatment offered. I'd decided then that I would never ruin my last days on earth by that painful, futile treatment that was all that there was on offer then. So glad to hear that there are new drugs on trial that will hopefully kill only the cancer and not the patient, especially if it's me!