Chair, Anthony R. Mato, MD, MSCE, Kristen Battiato, MSN, RN, AGNP-C, Dipti Gupta, MD, MPH, and Amber C. King, PharmD, BCOP, prepared useful Practice Aids pertaining to B-cell cancers for this CME/MOC/NCPD activity titled “Interprofessional Perspectives on Safety Management With Targeted Therapy for B-Cell Malignancies.” For the full presentation, downloadable Practice Aids, and complete CME/MOC/NCPD information, and to apply for credit, please visit us at http://bit.ly/3cHX3zm. CME/MOC/NCPD credit will be available until October 3, 2023.

1. Tools for Understanding BTK Inhibitors: Dosing and Safety1-7
Full abbreviations, accreditation, and disclosure information available at PeerView.com/ECV40
CLL/SLL
Agent
Acalabrutinib8
Ibrutinib9
Pirtobrutinib10
Zanubrutinib11,12
MCL MZL WM Dosing
FDA approved for
adult patients
FDA approved for
adult patients with
≥1 prior therapy
Phase 1/2 testing Phase 2 testing
100 mg orally every
12 hours until
disease progression
or unacceptable
toxicity
FDA approved for
adult patients with
or without del(17p)
FDA approved for
adult patients with
≥1 prior therapy
FDA approved for
adult patients with
≥1 prior anti-CD20–
based therapy
FDA approved for
adult patients
• MCL and MZL:
560 mg orally
once daily
• CLL/SLL and WM:
420 mgorally
once daily
Phase 3 testing
FDA approved for
adult patients with
≥1 prior therapy
FDA approved for
adult patients with
≥1 prior anti-CD20-
based therapy
FDA approved for
adult patients
160 mg orally twice
daily or 320 mg
orally once daily
Phase 3 testing Phase 3 testing Phase 2 testing Phase 2 testing
From the BRUIN trial:
200 mg orally
daily until disease
progression or
unacceptable
toxicity
BTK Inhibitor Regulatory Status and Dosing Recommendations

2. • Don’t give BTKi concomitantly with warfarin
•
For new-onset AF, consider nonwarfarin
anticoagulation and monitor
• Hypertension: manage with antihypertensives
•
Monitor for and manage cardiac arrhythmia/AF
and treat appropriately
• Monitor patients for signs of bleeding
•
Arthralgia: rule out other causes, monitor, and use
supportive care for lower-grade events
–
Dose reduction once symptoms affect ADLs,
dose holds for higher-grade arthralgia
•
Monitor for infections and secondary malignancies
•
Headaches commonly occur early in therapy
with acalabrutinib and typically resolve in
1-2 months; manage with acetaminophen
and caffeine
• Monitor for neutropenia (particularly
with zanubrutinib)
In real-world settings, BTKi toxicity appears to be the most common reason for treatment discontinuation
in the frontline and relapsed/refractory settings. More selective covalent BTK inhibitors appear to have fewer off-target
effects leading to AEs versus ibrutinib.13
Understanding the spectrum of treatment-emergent
AEs with BTK inhibitors is an important first step
toward effective toxicity management
Management approaches for BTKi AEs are
available for all currently approved agents used
in B-cell cancer settings
Selected Clinical Notes
Additional Important Toxicities
Common Toxicities
Dermatologic
changes
Atrial
fibrillation Arthralgia Infection
Ventricular
arrhythmia
Fatigue
Diarrhea Hypertension Bleeding Cytopenias
Tools for Understanding BTK Inhibitors: Dosing and Safety1-7
Full abbreviations, accreditation, and disclosure information available at PeerView.com/ECV40
1. NCCN Clinical Practice Guidelines in Oncology: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. Version 1.2022. https://www.nccn.org/professionals/physician_gls/pdf/cll.pdf. 2. Lipsky A, Lamanna N. Hematology Am Soc Hematol Educ Program. 2020;1:336-345. 3. Byrd JC et al.
ASCO 2021. Abstract 7500. 4. Hillmen P et al. EHA 2021. Abstract LB1900. 5. Mato AR et al. Lancet. 2021;397:892-901. 6. Mato AR et al. Blood. 2016.28:2199-2205. 7. Mato AR et al. Haematologica. 2018;103:874-879. 8. Calquence (acalabrutinib) Prescribing Information. https://www.accessdata.fda.
gov/drugsatfda_docs/label/2017/210259s000lbl.pdf. 9. Imbruvica (ibrutinib) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205552s002lbl.pdf. 10. https://clinicaltrials.gov/ct2/show/NCT04666038. 11. https://www.cancernetwork.com/view/sequoia-trial-
meets-primary-pfs-end-point-improvement-with-frontline-zanubrutinib-for-cll. 12. Brukinsa (zanubrutinib) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/213217s000lbl.pdf. 13. Kaptein A et al. ASH 2018. Abstract 1871.

3. Managing Ibrutinib-Associated AF1
Full abbreviations, accreditation, and disclosure information available at PeerView.com/ECV40
1. Ganatra S et al. JACC Clin Electrophysiol. 2018;4:1491-1500.
12
Use beta blocker
• Avoid non-DHP CCB (CYP450 3A4 inhibitor, increases ibrutinib level)
• Avoid digoxin (P-gp substrate, ibrutinib increased digoxin level)
• Add CCB with ibrutinib dose reduction and close monitoring or
temporary withholding of ibrutinib after discussion with a
hematologist OR
• Add digoxin at lower dose 6 hours prior to or after ibrutinib dose
with close monitoring of plasma levels and development of toxicity
Persistent rapid ventricular rate, severe symptoms, persistent reduced LVEF, or refractory HF
Continue beta blocker
Ibrutinib-associated AF
Assess suitability for anticoagulation
• High CHADS2VASc score/low HAS-BLED score
• No prior bleeding events
• Normal platelets, Hb, and INR
Consider anticoagulation
• Choose an agent based on individual patient profile and
preference
– LMWH if normal Cr
– Caution with Factor Xa inhibitors
– Avoid direct thrombin inhibitors
Rhythm control strategy
(cardioversion and
anti-arrhythmic medications)
Assess echocardiogram, Cr,
electrolytes, CBC, INR, and TSH
Rate control strategy preferred
due to:
• High likelihood of recurrence
on ibrutinib
• Need for uninterrupted
anticoagulation after
cardioversion
Hemodynamically unstable Hemodynamically stable
Yes
No Adequate rate control achieved

4. Tools for Understanding BCL-2 Inhibitor Dosing and Safety
Full abbreviations, accreditation, and disclosure information available at PeerView.com/ECV40
1. Venclexta (venetoclax) Prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208573s009lbl.pdf.
Venetoclax Dosing Schedule for Ramp-Up Phase in Patients With CLL/SLL
400 mg
400 mg
Week
5
20 mg
Week
1
50 mg
Week
2
100 mg
Week
3
200 mg
Week
4
Myelosuppression
TLS GI events
Infections
• Manage with dose
interruption/reduction
• For grade ≥3, consider G-CSF
and/or antibiotics
• Assess risk in all patients
• Pretreatment CT scan to
assess internal
lymphadenopathy
• Premedicate with
antihyperuricemics;
ensure adequate hydration
• Diarrhea: rule out
infectious causes; treat
with antidiarrheals and
PO hydration
• Nausea: adjust dose timing
and use antiemetics
• Grade 3/4: withhold until
resolution and resume at
same or reduced dose
Venetoclax is
FDA approved for
the treatment of adult
patients with CLL/SLL,
with or without
del(17p), who have
received at ≥1 prior
therapy1

5. CLL Society Resources
Full abbreviations, accreditation, and disclosure information available at PeerView.com/ECV40
Ask the Experts
CLL Support Groups
Email Alerts for CLL
Breaking News
cllsociety.org/ask-the-expert
cllsociety.org/cll-specific-
patient-support-groups
cllsociety.org/cll_alerts
The mission of the CLL Society is to be an
inclusive, patient-centric, physician-curated
nonprofit organization that addresses the
unmet needs of the CLL community through
patient education, advocacy, support, and
research. Here you will find highlights of helpful
resources from cllsociety.org to better inform
your practice.
Test Before Treat™ Resources and Handouts
cllsociety.org/cll-101/test-before-treat
Current NCCN and iwCLL guidelines indicate the importance
of obtaining biomarker testing before the first treatment
and again before every subsequent therapy
Patient Education Toolkit Binder
cllsociety.org/patient-education-toolkit
Free resource for healthcare providers and CLL/SLL patients
TM