The latest videos on the CLL channel vjhemonc.com/subject/chroni.... complement some of the recent posts on new treatment developments. Currently we have, with the interview time in minutes and seconds given after each video:-
- Epcoritamab monotherapy and combinations in R/R CLL and Richter’s syndrome - 1:00
Barbara Eichhorst • 14 Jun 2023
- Genomic evolution & resistance to pirtobrutinib in covalent BTK inhibitor pre-treated CLL - 1:32
Krish Patel • 15 Jun 2023
The CLL Treatment Infection Model: identifying patients with CLL at high risk of infections - 3:41
Wow. Thanks for posting this Neil. There are some seriously exciting updates in there (I may have gone a little wider into some of the videos!) and the future of personalized immunotherapy.
The data on using MRD status alone for monitoring disease post treatment, trialling of 3 months treatment on Ibrutinib & venetoclax to put CLL back into an indolent state. Personally, just the recognition that cellular or clonal changes manifest earlier than physical disease progression, or as Spike Milligan used as his epitaph: I told them I was ill. 😳
Ty Neil for sharing- there's so much information regarding BTKi especially the 1st generation ibrutinib vs 2nd generation acalabrutinib vs 3rd generation pirtobrutinib that is more tolerable for CLL folks. Curious as to why they don't put folks right away on pirtobrutinib (which I think they approved on Jan).
In theory you could first start treatment on pirtobrutinib. I'd say the concern is that not only are we still awaiting FDA approval for CLL, but the accelerated FDA approval was for MCL in January for second or later line treatment, including prior treatment with a BTKi. So while pirtobrutinib can be prescribed off label for CLL, a specialist would be going considerably out on a limb to prescribe it for first label CLL use. (I think there's concern that remissions may not last as long on non-covalently bonding BTKi drugs as those that covalently bond. We'd need head to head first line trials with randomisation to be sure. Maybe the manufacturer will find such a study to try and boost their market share?)
There's also the fact that we have way more long term data on the covalently bonding BTKi drugs, plus we know that the switch to pirtobrutinib usually works after resistance to a covalent bonding BTKi drug occurs.
Neil
* FDA approved Jaypirca™ (pirtobrutinib, 100 mg & 50 mg tablets) for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a Bruton's tyrosine kinase (BTK) inhibitor. (My emphasis, which, per the introduction must be a covalent bonding BTKi. We need to keep in mind that this approval was via the accelerated approval pathway approach, which was introduced by the FDA to speed access to new cancer drugs, but at the risk that later contraindications can appear as has happened with idelalisib and other PI3K inhibitors.)
Loxo/Eli Lili are already sponsoring a phase 3 clinical trial titled “Randomized Study of Pirtobrutinib (LOXO-305) Versus Ibrutinib in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (BRUIN-CLL-314) one of the criteria is treatment naïve patients. Clinical trials aren’t approved first line treatments, but they’re testing.
Ty Neil - you thoroughly explained the "why" to me. There's so much to learn regarding these BTK inhibitors! Thank you so much for sharing your expertise with us all.
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