Who will pursue treatments for low NK cell patients?

[Jaybee00]

Given the fact that the Fluge/Haukeland phase 2 Daratumumab trial will exclude patients with low NK cell #s, will anyone follow up on this group of patients?

Or should Fluge’s group have included a couple of low NK cell patients who underwent “pre-treatment” for low NK cells, with things like blueberries and salicinium?

 

[V.R.T.]

Given the fact that the Fluge/Haukeland phase 2 Daratumumab trial will exclude patients with low NK cell #s, will anyone follow up on this group of patients?

Or should Fluge’s group have included a couple of low NK cell patients who underwent “pre-treatment” for low NK cells, with things like blueberries and salicinium?

I assume this stuff will be investigated after dara p2 if it succeeds but that is a way off. Personally I wish they could have gone straight to a larger phase 3 with mostly high nk cell patients but subgroups of artificially raised and low NK cell patients.

If there trial is postive and it was just a case of raising them in low NK patients so dara works better that would be dream scenario.

 

[Jonathan Edwards]

If daratumumab turns out to work in the people with NK cells then we have a means of working out what is going on and what needs to be done for those without. No doubt F & M will pursue both groups and hopefully a lot of other people as well. It may require a different anti-CD38 or it may mean that there is a subgroup that are not CD38-dependent. They might need a completely different approach but at least we may have some idea what.

 

[V.R.T.]

Does the anti CD38 drug Scheibenbogen is using also require NK cells to work?

it may mean that there is a subgroup that are not CD38-dependent. They might need a completely different approach but at least we may have some idea what.

Do you have any speculations about what sort of approach the other subgroup might need in this scenario?

 

[Kitty]

Are we actually sure yet about the NK link? There seems to be suggestive evidence, but with such small cohorts in the initial trial presumably there's still a lot learn about individual responses.

 

[Jaybee00]

No doubt F & M will pursue both groups and hopefully a lot of other people as well.

By “hopefully a lot of other people as well” do you mean, for example, patients with fibromyalgia, post treatment Lyme, and idiopathic fatigue that doesn’t meet ME/CFS criteria?

 

[Jonathan Edwards]

By “hopefully a lot of other people as well” do you mean, for example, patients with fibromyalgia, post treatment Lyme, and idiopathic fatigue that doesn’t meet ME/CFS criteria?

I was meaning other researchers as well as F& M

 

[Jaybee00]

Ah ok, misunderstood.

 

[fst]

Does the anti CD38 drug Scheibenbogen is using also require NK cells

It seems that Isatuximab is less dependent on NK cells.
From the hallucination machine:

Izatuximab does not require high NK cell counts to the same degree as daratumumab, thanks to its ability to directly induce apoptosis and stronger CDC activity.

The references it gives for this play out (e.g. Therapeutic Opportunities with Pharmacological Inhibition of CD38 with Isatuximab), but I am in no position to judge their quality.

 

[V.R.T.]

It seems that Isatuximab is less dependent on NK cells.
From the hallucination machine:


The references it gives for this play out (e.g. Therapeutic Opportunities with Pharmacological Inhibition of CD38 with Isatuximab), but I am in no position to judge their quality.

Interesting! If this is the case then the Scheibenbogen trial will be worth keeping an eye on if it goes ahead.

I hope they measure NK cells before treatment too.

 

[forestglip]

It seems that Isatuximab is less dependent on NK cells.
From the hallucination machine:


The references it gives for this play out (e.g. Therapeutic Opportunities with Pharmacological Inhibition of CD38 with Isatuximab), but I am in no position to judge their quality.

Pulling out some quotes about the difference from a quick scan:

Isatuximab is the only CD38 antibody that is capable to induce direct apoptosis; daratumumab, MOR202, and TAK-079 induce apoptosis upon secondary cross-linking

Isatuximab was selected in an antibody screen for further evaluation based on its ability to directly trigger MM cell death in the absence of cross-linking agents and independent of effector cells [12,13]. Daratumumab and TAK-079 lack the ability to directly induce MM cell death

Daratumumab-induced ADCC can be augmented by lenalidomide and bortezomib, whereas isatuximab and pomalidomide demonstrate synergistic ADCC induction both in vitro and in vivo (Figure 3) [12]. Isatuximab demonstrates potent direct killing activity based on a greater increase in apoptosis of CD38-expressing cancer cells [12]. Moreover, isatuximab led to a dose-dependent inhibition of CD38 enzymatic activity, while daratumumab under the same experimental conditions produced a more limited inhibition without obvious dose response (Figure 3).

Moreover, a key distinguishing feature of isatuximab is its capability to inhibit CD38 ectoenzymatic activity

 

[V.R.T.]

Pulling out some quotes about the difference from a quick scan:

Sounds like if it's CD38 inhibition rather than plasma cell depletion we want this drug might be more effective than daratumumab?

 

[ryanc97]

From ChatGPT both ways Isa is better than Dara. It targets CD38 better and also I think somehow reduces fraticide of NK cells.

It’s just a superior Dara version apparnelty.