Andre H. Goy, MD, Owen A. O’Connor, MD, PhD, Stephen D. Smith, MD, and Michael Wang, MD, prepared useful practice aids pertaining to B-cell malignancies for this CME activity titled "Exploring the Present and Future of BTK Inhibition in B-Cell Malignancies: Expert Insights on Practical Implications for Patient Management." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2rvynmE. CME credit will be available until December 20, 2019.

1. Access the activity,“Exploring the Present and Future of BTK Inhibition in B-Cell Malignancies: Expert Insights on Practical Implications for Patient Management,”
at www.peerview.com/KKT40.
A Clinical Guide to BTK Inhibitors
Considerations for Use in B-Cell
Non-Hodgkin Lymphoma
PRACTICE AID
This Practice Aid has been provided as a quick reference to help learners apply the information to their daily practice and care of patients.
• MCL with at least 1 prior therapy
• CLL/SLL
• CLL/SLL with 17p deletion
• WM
• MZL requiring systemic therapy and with
at least 1 prior anti-CD20–based therapyIndications
• CYP3A inhibitors
• CYP3A inducers
DDIs
Neutropenia,
thrombocytopenia,
diarrhea, anemia,
musculoskeletal pain, rash,
nausea, bruising, fatigue,
hemorrhage, and pyrexia
Adverse Events
in ≥20% Pts
• Avoid use of ibrutinib
in patients with severe
baseline hepatic
impairment
• In patients with mild or
moderate impairment,
reduce ibrutinib dose
Use in Special
Populations
Testing for BTK and PLCG2 mutations
may be useful in patients receiving
ibrutinib and suspected of having
progression. BTK and PLCG2 mutation
status alone is not an indication to
change treatment.
NCCN
Recommendations2
Monitor pts for:
• Bleeding
• Infections and fever
• Cardiac arrhythmias
• Elevated BP
• TLS
• Secondary primary malignancies
Assess/advise:
• CBCs monthly
• TLS baseline risk
• Women to avoid pregnancy while
on drug and 1 mo after cessation,
and men to avoid fathering a child
during the same period
Safety
Considerations
• MCL/MZL: 560 mg orally once
daily
• CLL/SLL and WM: 420 mg orally
once daily
Dosing
O
N
N
N
N
N
H2N
O
Ibrutinib1

2. BTK: Bruton's tyrosine kinase; CLL: chronic lymphocytic leukemia; CYP3A: cytochrome P450 3A4; DDI: drug–drug interaction; MCL: mantle cell lymphoma; MZL: marginal zone B-cell lymphoma; NCCN: National Comprehensive Cancer Network; PPI: proton pump inhibitor;
SLL: small lymphocytic lymphoma; TLS: tumor lysis syndrome; WM: Waldenström’s macroglobulinemia.
1. Imbruvica (ibrutinib) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205552s002lbl.pdf. Accessed August 20, 2018. 2. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology. Chronic Lymphocytic Leukemia/Small
Lymphocytic Lymphoma. Version 2.2019. 3. Calquence (acalabrutinib) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/210259s000lbl.pdf. Accessed August 20, 2018.
Access the activity,“Exploring the Present and Future of BTK Inhibition in B-Cell Malignancies: Expert Insights on Practical Implications for Patient Management,”
at www.peerview.com/KKT40.
This Practice Aid has been provided as a quick reference to help learners apply the information to their daily practice and care of patients.
A Clinical Guide to BTK Inhibitors
Considerations for Use in B-Cell
Non-Hodgkin Lymphoma
PRACTICE AID
• Adult patients with MCL with at least
1 prior therapy
Indications
• CYP3A inhibitors
and CYP3A inducers
• Gastric acid–reducing
agents (PPIs)
DDIs
Anemia,
thrombocytopenia,
headache, neutropenia,
diarrhea, fatigue,
myalgia, and bruising
Adverse Events
in ≥20% Pts
• Advise women not to
breastfeed
Use in Special
Populations
NCCN also recommends acalabrutinib
for relapsed/refractory CLL (except
ibrutinib–refractory CLL with BTK
C481S mutations).NCCN
Recommendations2
Monitor pts for:
• Bleeding
• Signs and symptoms of infections
• Secondary primary malignancies
• Atrial fibrillation and atrial flutter
Assess/advise:
• CBCs monthly
• Pts to use sun protection
Safety
Considerations
• 100 mg orally approx. every
12 h; swallow whole with water
and with or without food
• Advise not to break, open,
or chew capsuleDosing
Acalabrutinib3
O
N
NH2
N
N
N
N
NH
O

3. Access the activity,“Exploring the Present and Future of BTK Inhibition in B-Cell Malignancies: Expert Insights on Practical Implications for Patient Management,”
at www.peerview.com/KKT40.
Selected Studies With BTK Inhibitors
Clinical Trial Landscape of B-Cell
Non-Hodgkin Lymphoma1
PRACTICE AID
Ibrutinib
Zanubrutinib
(BGB-3111)
Primary Endpoint(s)
Primary Endpoint(s)
TLS, DTL, PFS
CR, VGPR
PFS
PFS
PFS
PFS
PFS
Key: ˜ Active, not recruiting ˜ Currently recruiting
Phase 3 Clinical
Trials
Phase 3 Clinical
Trials
NCT03112174 (SYMPATICO)
Ibrutinib + venetoclax in previously treated patients with MCL
NCT03053440 (BGB-3111-302)
BGB-3111 vs ibrutinib in patients with WM
NCT02947347 (PERSPECTIVE)
Ibrutinib + rituximab in patients with treatment-naïve FL
NCT03336333 (BGB-3111-304)
BGB-3111 vs bendamustine + rituximab in patients with previously untreated CLL/SLL
NCT03462719 (GLOW/CLL 3011)
Ibrutinib + venetoclax vs chlorambucil + obinutuzumab for patients with newly diagnosed CLL/SLL
NCT02443077 (BMT CTN 1201/Alliance A051301)
Ibrutinib before and after SCT in patients with R/R DLBCL
FLAIR2
Ibrutinib monotherapy vs ibrutinib + rituximab vs ibrutinib + venetoclax vs FCR
in patients with treatment-naïve CLL/SLL

4. BTK: Bruton's tyrosine kinase; CLL: chronic lymphocytic leukemia; CR: complete response; DLBCL: diffuse large B-cell lymphoma; DLT: dose-limiting toxicities; FCR: fludarabine, cyclophosphamide, and rituximab; FL: follicular lymphoma; MCL: mantle cell lymphoma;
MRD- CR: minimal residual disease–negative complete response; NCCN: National Comprehensive Cancer Network; R/R: relapsed/refractory; SCT: stem cell transplant; SLL: small lymphocytic lymphoma; TLS: tumor lysis syndrome; TN: treatment naïve; VGPR: very good partial response;
WM: Waldenström’s macroglobulinemia.
1. https://clinicaltrials.gov/ct2/home. Accessed November 15, 2018. 2. https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-ibrutinib-rituximab-chronic-lymphocytic-leukaemia-flair#undefined. Accessed November 15, 2018. 3. National Comprehensive Cancer Network
(NCCN) Clinical Practice Guidelines in Oncology. B-Cell Lymphomas. Version 5.2018.
Access the activity,“Exploring the Present and Future of BTK Inhibition in B-Cell Malignancies: Expert Insights on Practical Implications for Patient Management,”
at www.peerview.com/KKT40.
This Practice Aid has been provided as a quick reference to help learners apply the information to their daily practice and care of patients.
Selected Studies With BTK Inhibitors
Clinical Trial Landscape of B-Cell
Non-Hodgkin Lymphoma1
PRACTICE AID
Acalabrutinib Primary Endpoint(s)
PFS
PFS
PFS
PFS
MRD- CR, time to first therapy
MRD- CR
Key: ˜ Active, not recruiting ˜ Currently recruiting
Phase 3 Clinical
Trials
NCT02475681 (Elevate CLL TN)
Acalabrutinib monotherapy vs acalabrutinib + obinutuzumab vs obinutuzumab + chlorambucil
in patients with previously untreated CLL/SLL
NCT02477696 (Elevate CLL R/R)
Acalabrutinib vs ibrutinib in previously treated patients with high-risk CLL/SLL
NCT02972840 (ACE-LY-308)
Acalabrutinib + bendamustine/rituximab vs bendamustine/rituximab
in patients with previously untreated MCL
NCT02970318 (ACE-CL-309)
Acalabrutinib vs investigator's choice of idelalisib + rituximab
or bendamustine + rituximab in R/R CLL/SLL
NCT03516617 (Phase 2)
Acalabrutinib ± obinutuzumab in patients with early stage CLL/SLL
NCT03580928 (AVO; Phase 2)
Venetoclax + obinutuzumab + acalabrutinib in patients with newly diagnosed CLL/SLL
NCCN Recommendation3
The NCCN believes that the best management for any patient with cancer is in a clinical trial. Participation in a clinical trial is especially encouraged.