@TargetedOnc @AHNtoday Thanks for having me here - great chat about CLL !

@TargetedOnc @AHNtoday I would everyone to keep in mind that enrolling in to clinical trials is of utmost importance without which none of what we have available currently would have been possible

@TargetedOnc @AHNtoday The future of CLL is bright. We are fortunate that we are moving away from chemotherapy and have many targeted agents to choose from. With that being said, significant improvements in treatments are still needed

@TargetedOnc @AHNtoday The combination of a BTK inhibitor, Venetoclax with or without an AntiCD20 in front-line CLL for a finite duration may also be practice-changing soon

@TargetedOnc @AHNtoday The emerging use of CAR-T cell therapy, as well as TIL therapy, is exciting and we have trials utilizing both technologies here at AHN. The approval of Pirtobrutinib will also be a welcome addition since it is effective in patients who develop resistance to current BTK inhibitors

@TargetedOnc @AHNtoday Focusing on developing treatments with a more finite duration would also benefit patients and hopefully, reduce the financial burden on the healthcare system as a whole

@TargetedOnc @AHNtoday A cure is still elusive. I don’t think we know what to do with MRD data yet and how best to use it. Sequencing of novel agents also remains a question

@TargetedOnc @AHNtoday Both are excellent choices and can be individualized towards the patient’s specific presentation, risk factors and goals as discussed in the prior questions

@TargetedOnc @AHNtoday The SOC would be the use of targeted agents rather than chemotherapy in most cases. There is no right or wrong answer though when choosing between a BTK inhibitor and a Venetoclax based regimen

@TargetedOnc @AHNtoday I also ask them to let me know if they are having any interventions, procedures or surgeries since BTK inhibitors have to be held pre and post surgery

@TargetedOnc @AHNtoday I also ask them not to skip doses and to let me know if other physicians they are seeing prescribe any medications since there might be interactions. This is also true if the patient would start any OTC meds

@TargetedOnc @AHNtoday I ask them to inform me immediately if they notice excessive bruising, bleeding, palpitations or light-headedness which could mean the patient might be exhibiting some of the side effects unique to BTK inhibitors (increased bleeding/bruising risk, arrhythmias)

@TargetedOnc @AHNtoday The tablet form was recently approved and being on a PPI or an H2 blocker is no longer an issue

@TargetedOnc @AHNtoday Previously, this would have affected my choice and I would have tried to get the patient off of it if I were to use Acalabrutinib because the capsule form is not absorbed while a patient is on a PPI

@TargetedOnc @AHNtoday Zanubrutinib is another good choice but is not yet FDA approved for use in patients with CLL in the frontline setting although it is part of the NCCN guidelines and can be used if needed

@TargetedOnc @AHNtoday I would choose Acalabrutinib because it is a second generation BTK inhibitor generally has lesser side effects than Ibrutinib. With its new tablet formulation, the patient’s use of a PPI is no longer an issue.

@TargetedOnc @AHNtoday The ELEVATE-RR study is also notable because it compared Acalabrutinib vs Ibrutinib and noted that Acalabrutinib is just as efficacious in CLL (relapsed) but also generally has fewer adverse reactions in some respects

@TargetedOnc @AHNtoday shows a better PFS than FCR as well as BR for younger or older patients respectively. The ELEVATE-TN trial showed efficacy of Acalabrutinib with or without Obinutuzumab in the front line setting

@TargetedOnc @AHNtoday The 5 year update from the CLL14 trial presented at this year’s ASCO influenced my choice of using Venetoclax plus Obinutuzumab for this patient. Other notable trials that influence my choices are the ECOG-E1912 trial and the ALLIANCE A041202 trials which showed that Ibrutinib

@TargetedOnc @AHNtoday Other factors to note that may sway my decision would be kidney function, logistical challenges for the patient if present as well as cardiac function, arrhythmias and whether a patient is on an anticoagulant or not.