Ibrutinib enhances chimeric antigen receptor T-cell engraftment and efficacy in leukemia

[kebnekaise]

"In this study, we demonstrated that ibrutinib treatment enhances the feasibility of generating CAR T cells from CLL patients."

"Given that 90% or more of patients with high-risk disease have an initial response to ibrutinib and typically remain on ibrutinib therapy for over 1 year, this time window may provide an optimal opportunity to collect T cells and to subsequently administer a potentially curative T cell–based therapy that would allow for cessation of drug treatment. "

"In summary, we have shown that long-term ibrutinib treatment reverses the dysfunction of T cells in CLL, which has implications for both the mechanism of action of ibrutinib and the potential use of T-cell therapies. The enhanced ex vivo proliferative capacity of CAR-redirected lymphocytes is a strong predictive indicator of their ability to engraft in vivo and mediate antitumor responses. This increased therapeutic potential is further supported by the synergistic effect of CAR T cells and ibrutinib in resistant models of acute and chronic leukemia. These data suggest that clinical trials with ibrutinib lead-in and then continued treatment could enhance the efficacy and engraftment of adoptively transferred T cells, including CAR T cells."

bloodjournal.org/content/12...

Irina, CLL Norway

[lartington]

can any of our clever members explain in simple terms what the above post means??thankyou

[AussieNeil Partner Administrator in reply to lartington]

It's certainly not easy to understand, but what I think the article is saying is:

"T- lymphocytes (T-cells) from CLL patients don't work very well due to the inhibitory effects of CLL. Many CLL treatments also inhibit T-cells. Successful T-cell therapy requires T-cells that can be easily encouraged to multiply after extraction from the patient or a donor (so we get enough clones to reinject).

T-cells in CLL patients treated with Ibrutinib actually recover their ability to function, what's more T-cells that exhibit this recovery are more likely to survive and multiply within the CLL patient and thus control the patient's CLL. So perhaps we can overcome the need for indefinite Ibrutinib treatment by combining it with CAR-T therapy within the first year of Ibrutinib treatment."

You can understand medical insurance companies may well be interested in this. If it costs them say $50,000 per year for their negotiated price for Ibrutinib (I presume this is how the costs are partly made more affordable) and patients live for an average of 10 years longer on Ibrutinib, that's a $500,000 per patient expense for the insurance company for just Ibrutinib! If CAR-T can be done for say $400,000 total cost per patient, that's a potential saving of $100,000 per patient!! (There's still the challenge of turning off T-cells when the CLL tumour is under control and hoping that this results in the recovery of immunoglobulin production...)

Perhaps this is how the high costs of CAR-T can be seen as viable?

Neil

[HAIRBEAR_UK Founder Admin in reply to AussieNeil]

This is exciting stuff and an innovative way to harness an effect of BCR inhibitors

i have heard recently that the costs for T cell therapies are expected to come down considerably in the future Another potential curative development angle that payers may be able to afford could be closer.!! WoW

Great post kebnekaise a very complex paper, but it sure does provide us with a lot and hope for the future, interesting stuff.

Nick.

[lartington in reply to AussieNeil]

thankyou, how very intertesting......... however as NICE seem pretty determined to keep the door closed to Ibrutinib here in the UK we will just have to watch and wait for any further developments!!!!

[HAIRBEAR_UK Founder Admin in reply to lartington]

I agree we will have to watch and wait to see how things develop with NICE both in the short term. and long term with the NICE/CDF reorganization under way as well and a new system about to commence..

It will be revealing to see how they respond to this next consultation for Ibrutinb use in R&R and 1st line CLL, The preliminary decision may still be reversed as the door is open for limited further discussion and negotiation with the company and consultation with all stakeholders?

It will also be interesting to see how .First line Ibrutinib use progresses through the New system too as this is now in with NICE.

Interestingly Ibrutinib for the R&R 1st line indication is now being assessed by the Scottish Medicines Consortium for NHSS use and their consultation has just commenced.

Hope

Nick

[PE1234 in reply to AussieNeil]

Thank you once again Neil for explaining this .i didn't understand it either but it's a lot clearer now .

Brenda

[Cllcanada Top Poster CURE Hero]

The breakthrough in this therapy will be 'off the shelf' T cells..two companies will be starting clinical trials this year...

But they still need an 'off' button on the T cells... might replace stem cell transplants, there is a move in that direction...

This is Novartis... CTL019... still a patient specific T cell therapy...very costly...

~chris