[rabbitParticipant]

Hi Leelynn and welcome to the forum.

I can do a hopeful story or two about high risk chromosomal abnormalities. 😀

I have an abnormality called +1q, which is a bit similar to del 1p in that they both affect chromosome 1. I also have the t(4, 14) abnormality.

Having 2 abnormalities is worse than 1.

Hopeful story 1. I was diagnosed in 2022. I am still in remission. My consultant talks about it being “functional normal risk”. In other words, my body is sort of ignoring the chromosomal abnormalities. My prognosis has therefore significantly improved.

Hopeful story 2. New treatments such as Elranatamab, Teclistamab, Talquetamab and Belantamab have all been approved in the UK and work pretty well for high risk patients such as your partner (and me). Further treatments such as trispecifics, in vivo CAR-T and CELMoDS are being trialed at the moment. If you are reading stuff onlne, you may be seeing out of date data on life expectancies etc. Things are improving rapidly.

Regards
Rabbit

[rabbitParticipant]

Hi David,

One extra thing to mention and then I will shut up 😀.

I don’t know if this will provide you with any reassurance…

I have done a lot of reading up on treatments and clinical trials of them. Although I am currently in remission, I have pondered my thoughts about my next line of treatment: I am currently hoping to persuade my consultant when the time comes to give me a bispecific antibody treatment.

Regards
Rabbit

[rabbitParticipant]

Hi David,

As an ex-scientist, it is relatively easy for me to find data (I generally know where to look) but I also know that that isn’t always the point.

Two issues come to mind in terms of bispecific side effect data and its relevance:
– As you said yourself, there are 3 bispecifics. Although I have stated above why I think that the relevant one for you is Talquetamab, your consultant may think differently.
– The clinical trials were done a few years ago. Since then, things have moved on for the better, so the data on side effects is more adverse than what you would face. The “step up” that is now being done was developed to reduce the probability and severity of cytokine release syndrome (CRS), for example. Tocilizumab, a drug that blocks inflammatory signaling and can rapidly control CRS symptoms, is now routinely given. Also it happened that some trials were done when Covid 19 was at its worst, so there were a lot of severe infections: hopefully you are vaccinated, and Covid has subsequently become much milder anyway.

• This reply was modified 1 week, 3 days ago by  rabbit.
• This reply was modified 1 week, 3 days ago by  rabbit.

[rabbitParticipant]

Hi David,

My sympathies: you have been through a lot of treatment and now face more.

I have not had bispecifics but I am geeky enough to read a lot 😀.

Belantamab gets the immune system to attack the BCMA antigen. Since that has stopped working, that probably means that your myeloma cells have adapted their BCMAs (similar to bacteria getting resistant to an antibiotic). That would make the bispecifics teclistamab and elranatamab less effective.

The other approved bispecific is talquetamab, which targets the GPRC5D antigen instead. It’s my best guess that that is what your consultant is thinking about.

The regime for bispecifics is that you would be given a few “step up” doses over a couple of weeks to see how you get on and to let your immune system respond steadily. Then you would get regular doses, typically weekly for some months then less frequently.

Side effects: Warning you may not want to read the rest of this!
Unfortunately, people also have GPRC5D antigen in cells on the tongue, skin and nails, so a metallic taste and skin rashes are common, (as well as changes to nails such as brittleness).
Then there is a lot of infection risk.
There is cytokine release syndrome, where you body attacks myeloma cells too enthusiastically and your body struggles to cope (that’s why the step up is important – the attack is more gentle on your body).
Then there is neurological toxicity. Less common but can include confusion and brain fog.
Blood counts can become low, although transfusions can help with that.

Regards
Rabbit

• This reply was modified 1 week, 6 days ago by  rabbit.

[rabbitParticipant]

Hi Chellem and welcome to the forum.

I am curious: going on to maintenance after 4 cycles is unusually soon. Around 6 months of treatment is more typical (with or without a stem cell transplant about 4 cycles in). Is there any reason? It could mean that you have responded exceptionally well to treatment!

Anyway, I was on dara and lenalidomide maintenance for over 2 years. The side effects of lenalidomide weren’t too bad for a long time, but I had to reduce the dose (semi-diarrhoea, fatigue and low platelets) and then come off it (low platelets). I am still on dara.

I am still in remission: 3 years now!

Regards
Rabbit

[rabbitParticipant]

Hi Najmah,

You mention a few different things.

– Yes, Zometa is a routine infusion that people usually get.

– The advice that I got from my nurse was that it often causes “flu like symptoms”. Fatigue is consistent with that, and it caused me fatigue. Nausea is not a Zometa side effect that I am familiar with, though.

– I just read up on Adcal using Chat-GPT. It contains both Calcium and vitamin D3. Chat-GPT then went out of its way to say not to take it within 4 hours of a bisphosphonate (such as Zometa). I am just passing the message on.

– Yes, Bortezomib can cause constipation. You are doing pretty much all the right things. The only extra thing that I can suggest is – if you are able to – is to exercise. For me, constipation came and went a bit.

– Another thing to mention. If you are taking vitamin C supplements or green tea extracts, don’t take them close to (within a day of) Bortezomib, as they can stop it from working.

I hope that this is some help.

Regards
Rabbit

[rabbitParticipant]

Hi steviej73 and welcome to the forum.

You have clearly been through a lot, and have to go through more.

What treatment are you going to have?

Regards
Rabbit

[rabbitParticipant]

Hi tiger108,

My goodness you have been through hell!

All the best for you.

Regards
Rabbit

[rabbitParticipant]

In the context of multiple myeloma, IgD refers to immunoglobulin D, one of the five main classes of antibodies produced by plasma cells (the others are IgG, IgA, IgM, and IgE).

IgD myeloma is a relatively rare subtype of multiple myeloma, accounting for about 1–2% of cases. In this form, the malignant plasma cells produce excessive amounts of IgD antibody.

Regards
Rabbit

[rabbitParticipant]

Hi Sammy65,

I would agree to disagree with you on CAR-T: I would describe it as personalised immunotherapy.

I agree with you that CAR-T has the big advantage of being ‘once and done’ with implications for everything from the side effects being shorter term to easier logistics (fewer hospital trips).

I have been looking at papers from the latest ASCO (cancer conference) in Chicago. Phase 1 results of in vivo CAR-T treatment KLN-1010 are looking promising: 18 patients all MRD negative (no myeloma cells detected although – before readers of this get too excited – some are probably lurking) so far and side effects have not been too bad.

Regards
Rabbit

[rabbitParticipant]

Hi Sammy,

I was about to reply to your previous email when it disappeared! I was puzzled – there is so much spam on this forum, and then the moderators delete a genuine post? 😀

This is a slight change of topic, but still relevant to this forum. You said “As well as its strong clinical place, I tried to buy time for a possibility of a CAR-T which is still not available in the UK on NHS today. I am aware that clinical recommendations are that a patient should have a CAR-T first and then bi-specifics in the further relapse and not the other way round.”

I will explain first in a bit more detail, as us patients and carers should I think learn this stuff (I am simplifying a bit below).

Many of the newer treatments are immunotherapy: they enhance the body’s normal immune system so that it attacks myeloma cells. As myeloma cells are basically mutated forms oh healthy cells, the immunotherapy gets the immune system to attack bits (antigens) of myeloma cells that are not in the healthy cells.

Three of these differences have the catchy names of CD38, BCMA and GPRC5D. For example, Daratumumab and Isatuximab target CD38.

Many of the new treatments, including the CAR-T ones and the bispecific antibody treatments Elranatamab and Teclistamab target BCMA.

The issue is that myeloma cells can develop ‘resistance’ to a treatment: one reason why it generally comes back. With a treatment that targets an antigen, the myeloma may adapt over time by having less of that antigen.

Therefore, if you have a treatment like Elranatamab or Teclistamab that targets BCMA, it can make other treatments targeting BCMA less effective.

Background over!

Sammy65, you are right that no CAR-T treatment is approved in the UK yet. However, if you have a BCMA-targeting bispecific, the myeloma do seem to reverse their adaptation after some time. Also, the MajesTEC-3 and MajesTEC-9 clinical trials are showing that Teclistamab – with (MajesTEC-3) or without (MajesTEC-9) Daratumumab – is a very effective treatment (though with some unpleasant side effects). Maybe CAR-T simply isn’t such an important option anyway.

Meanwhile, Talquetamab is an approved bispecific treatment which targets GPRC5D, so is unaffected by being refractory to BCMA.

Then there are the treatments that are not immunotherapy…

Regards
Rabbit

[rabbitParticipant]

Hi Peter,

The sequence of my treatment went:
– ‘Induction phase’. 4 cycles (a cycle is 4 weeks) of Daratumumab weekly, Revlimid = Lenalidomide daily, Velcade = Bortezomib weekly and Dexamethazone (‘Dex’) twice a week. Thalidomide is similar to Lenalidomide, with a week off for each cycle.
– Break in treatment, then stem cell harvesting.
– ‘Consolidation phase’ the same treatment as in the induction phase, for 2 more cycles. Apart from not having a transplant, this is the normal treatment.
– Maintenance. This was originally Daratumumab and Dex, once per cycle, and Lenalidomide daily (with a week off per cycle). The Lenalidomide dose was reduced from the start (because maintenance is about preventing/delaying myeloma returning), the Dex likewise. The Lenalidomide was further reduced and then stopped due to side effects. Daratumumab is ongoing.

I am ‘high risk’ (= my chromosomes are messed up) which makes my myeloma more aggressive than most so this is more maintenance than usual.

Despite that, I have just celebrated 3 years in remission.

One thing that probably helps: I am doing what I reasonably can in terms of healthy lifestyle: lots of exercise, vegetarian and eating healthily, don’t drink much…

Regards
Rabbit

[rabbitParticipant]

Hi Larry,

If you are saying that you have smouldering myeloma, then I can help on that one.

If that is the case, that would mean that you do not have active myeloma.

https://bloodcancer.org.uk/understanding-blood-cancer/myeloma/smouldering-myeloma/

Normally, smouldering myeloma is only monitored. However, in a few cases, patients are just starting to be given preventative chemo. It’s early days on that, though.

Regards
Rabbit

[rabbitParticipant]

Hi Larry and welcome to the forum.

You have been through a lot: first shingles, then a myeloma diagnosis.

It sounds as though you were only given Dexamethazone at first, even though you had paraproteins (which are a major indication of MGUS, smouldering myeloma and active myeloma), which is puzzling. Do you know what myeloma treatment is being planned? The NHS standard is a combo of 4 chemo drugs: Daratumumab, Velcade (also known as Velcade), Thalidomide and Dexamethazone. However, some patients are given alternatives to that.

There are also likely to be other drugs, possibly including Acyclovir, to prevent a shingles repeat.

The vomiting is concerning. Any idea what is causing that?

If you have any questions, please ask away. Many of us have had myeloma for years.

Regards
Rabbit

[rabbitParticipant]

Hi cjleeds,

No problem: I was simply quoting one of our new AI overlords 😀.

However, I will tell you my plan, although it is subject to change, as new clinical trials and treatments come out, and depending on what is most suitable for me at the time.

For me, the belantamab side effects relating to eyesight are offputing. I had, like you, the experience of eyesight deterioration from Dexamethazone already. Once bitten, twice shy, especially as much of my semi-retirement involves reading, looking at nature, watching videos etc. I even use my eyes on the little work that I do these days!

The MajesTEC-3 trial showed that Teclistamab and Daratumumab are a very effective combo. It can come with its own side effects, such as cytokine release syndrome (CRS) and neurotoxicity and they could be tough going in themselves. CRS would be likely to be for just the first few days though. The biggie for me might be infection risk, and I have heard of cases where reduced immunity goes on for years. However, I have done lots of holidays over the last couple of years, so if I have to tuck myself away with lots of books and Youtube in my garden, then so be it.

First, though, I have to hold out for Teclistamab and Dara to be a second line treatment instead of fourth line and later. The MajesTEC-3 results were so good that maybe that will come sometime soon. I can hope!

Regards
Rabbit

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