Cyrus Khan, MD

Lymphoma, Malignant Hematology, Transplant & Cellular Therapy, Allegheny Health Network Cancer Institute @AHNtoday

[Cyrus Khan, MD @CyrusKhann]

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

[Cyrus Khan, MD @CyrusKhann]

@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

[Cyrus Khan, MD @CyrusKhann]

@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

[Cyrus Khan, MD @CyrusKhann]

@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

[Cyrus Khan, MD @CyrusKhann]

@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

[Cyrus Khan, MD @CyrusKhann]

@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

[Cyrus Khan, MD @CyrusKhann]

@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

[Cyrus Khan, MD @CyrusKhann]

@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

[Cyrus Khan, MD @CyrusKhann]

@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

[Cyrus Khan, MD @CyrusKhann]

@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

[Cyrus Khan, MD @CyrusKhann]

@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

[Cyrus Khan, MD @CyrusKhann]

@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)

[Cyrus Khan, MD @CyrusKhann]

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

[Cyrus Khan, MD @CyrusKhann]

@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

[Cyrus Khan, MD @CyrusKhann]

@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

[Cyrus Khan, MD @CyrusKhann]

@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.

[Cyrus Khan, MD @CyrusKhann]

@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

[Cyrus Khan, MD @CyrusKhann]

@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

[Cyrus Khan, MD @CyrusKhann]

@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

[Cyrus Khan, MD @CyrusKhann]

@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.