2) .@tobyeyre82 discusses here more on #pharmacology, patient selection for #CAR_T, and sequencing of CAR T tx in the management of #CLL. Until recently, this approach was not as successful as it has been in #B_cell #leukemia and #lymphoma.
— @onc_ce (@onc_ce) July 18, 2023
4) 🔬 CART = Chimeric antigen receptor (CAR) T-cell therapies. #CARs are recombinant receptors for antigens that redirect the specificity & function of T lymphocytes &/or other immune cells in a single molecule.
— @onc_ce (@onc_ce) July 18, 2023
6) Anti-#CD19 #CART therapy is in further development in each of these disease entities with the aim to bring CART therapy further forward in the treatment pathway for patients. Ongoing randomised trials will help us understand where these treatments are best applied.
— @onc_ce (@onc_ce) July 18, 2023
7b) Although #CLLsm was the earliest disease in which CAR-T therapies were studied, development has been slower than other B cell malignancies and has yet to lead to regulatory approval.
— @onc_ce (@onc_ce) July 18, 2023
9) Producing functional CAR T cells capable of both in vivo expansion and adequate persistence has proved a challenge, and there has been a lack of data, until recently, demonstrating efficacy in #CLL patients resistant to both a BTK inhibitor #BTKi and #venetoclax.
— @onc_ce (@onc_ce) July 18, 2023
11) To help potentially overcome the issue of T cell dysfunction in #CLL, #ibrutinib was added pre Anti-CD19 CAR T cell therapy for 2wk & for ≥ 3mo post infusion in 19 high risk CLL patients. Encouraging responses: ORR iwCLL 83%, MRD-negativity 61%)
— @onc_ce (@onc_ce) July 18, 2023
🔓 https://t.co/dPV4gMOGO6
13) Recently, data from the #TRANSCEND_004 trial has demonstrated high response rates and #MRD-negativity in patients with high risk, relapsed/refractory #CLL. See my prior tweetorial on these results, still available for CE/#CME credit, at https://t.co/kfW7UBIFLb.
— @onc_ce (@onc_ce) July 18, 2023
15) Whether the specific T-cell enrichment process in #Liso_cel production has influenced these results remains an important question to answer in the future.
— @onc_ce (@onc_ce) July 18, 2023
16b) … & where CART treatment will optimally be sequenced in the #CLLsm treatment pathway.
— @onc_ce (@onc_ce) July 18, 2023
So what do we know about patient selection and treatment sequencing with #CAR_T so far?
17b) cont
— @onc_ce (@onc_ce) July 18, 2023
🔬No active, uncontrolled infections, including #hepatitis B, hepatitis C, or #HIV
🔬patient has adequate performance status & organ function
🔬patient has no clinically relevant comorbidities
See 🔓 https://t.co/wpqJCtn9kH
18b) It is also important that patients are able to withstand unique immune-related toxicities w/#CART & often must be able to travel for treatment.
— @onc_ce (@onc_ce) July 18, 2023
19b) Covalent #BTKi & #venetoclax-based tx form the standard treatment approaches in early lines of the #CLL pathway. It is likely that at least initially, pts will have been exposed to these agents prior to #CART therapy . . .
— @onc_ce (@onc_ce) July 18, 2023
19d) Per https://t.co/l4w5yChPaG, #CAR T-cell therapy for #CLL is evolving to next generation based on learning from several clinical trials, such as #TRANSCEND. pic.twitter.com/5f0a3vDSN8
— @onc_ce (@onc_ce) July 18, 2023
19f) More studies are needed to better understand T cell dysfunction in #CLL environment and to improve #CAR_T function by molecular, transcriptional and epigenetic modulation.
— @onc_ce (@onc_ce) July 18, 2023
20b) … ‘off the shelf’ natural killer CAR, ‘off the shelf’ allogenic CART, and altering CART constructs, e.g. co-stimulatory domains. See 🔓 https://t.co/UPOonzdWjr . pic.twitter.com/teQNLdCIGp
— @onc_ce (@onc_ce) July 18, 2023
21b) The answer is 4; #CD19 expression is present in #CLLsm, but the other 3 issues have slowed progress in #CART development.
— @onc_ce (@onc_ce) July 18, 2023
Now, re the #TRANSCEND 004 CLL study, you have to know your study population! MRD-negativity rate with #liso-cel in CLL patients from TRANSCEND 004 was
22) And you just earned 0.5hr 🆓CE/#CME. Just go to https://t.co/3iW8CFZcQj and claim your certificate! Tracking rapid advances in the management of #pan_lymphoma is challenging. Let @tobyeyre82 and our other expert faculty help you keep up as we support our patients! pic.twitter.com/myOehSb5ng
— @onc_ce (@onc_ce) July 18, 2023