Michael Wang, MD, and Michael J. Keating, MB, BS, prepared useful Practice Aids pertaining to B-cell malignancies for this CME activity titled "Integrating BTK Inhibitors Into the Management of B-Cell Malignancies: How Is Evidence Driving Patient Care?" For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2zChqfa. CME credit will be available until October 11, 2019.

1. Considerations for Use of BTK Inhibitors
in B-Cell Non-Hodgkin Lymphoma
PRACTICE
AID
Access the activity,“Integrating BTK Inhibitors Into the Management of B-Cell Malignancies: How Is Evidence Driving Patient Care?”
at www.peerview.com/XHZ40.
CLINICAL GUIDE
This Practice Aid has been provided as a quick reference to help learners apply the information to their daily practice and care of patients.
Adverse
Events in
≥20% Pts
Ibrutinib1 • 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 therapy
• MCL/MZL: 560 mg orally
once daily
• CLL/SLL and WM:
420 mg orally once daily
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
Neutropenia,
thrombocytopenia, diarrhea,
anemia, musculoskeletal
pain, rash, nausea, bruising,
fatigue, hemorrhage,
and pyrexia
• 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
DDIs
• CYP3A inhibitors
• CYP3A inducers
NCCN Recommendations2
Testing for BTK and PLCG2 mutations may be useful in patients with CLL
receiving ibrutinib and suspected of having progression. BTK and PLCG2
mutation status alone is not an indication to change treatment.
DosingIndications
Safety
Considerations
X
O
N
N
N
N
N
H2N
O

2. Considerations for Use of BTK Inhibitors
in B-Cell Non-Hodgkin Lymphoma
BTK: Bruton's tyrosine kinase; CLL: chronic lymphocytic leukemia; CYP3A: cytochrome P450 3A4; DDI: drug–drug interactions; 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. B-Cell Lymphomas. Version
4.2018. 3. Calquence (acalabrutinib) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/210259s000lbl.pdf. Accessed August 20, 2018.
PRACTICE
AID
Access the activity,“Integrating BTK Inhibitors Into the Management of B-Cell Malignancies: How Is Evidence Driving Patient Care?”
at www.peerview.com/XHZ40.
CLINICAL GUIDE
Adverse
Events in
≥20% Pts
Acalabrutinib3
• Adult patients with MCL with at least
1 prior therapy
• 100 mg orally approx.
every 12 h; swallow whole
with water and with or
without food
• Advise not to break, open,
or chew capsule
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
Anemia,
thrombocytopenia,
headache,
neutropenia, diarrhea,
fatigue, myalgia,
and bruising
• Advise women not
to breastfeed
Use in
Special
Populations
DDIs
• CYP3A inhibitors and
CYP3A inducers
• Gastric acid–reducing
agents (PPIs)
NCCN Recommendations2
NCCN also recommends acalabrutinib for relapsed/refractory CLL
(except ibrutinib refractory CLL with BTK C481S mutations).
DosingIndications
Safety
Considerations
X
O
N
NH2
N
N
N
N
NH
O

3. Selected Studies With BTK Inhibitors
in B-Cell Non-Hodgkin Lymphoma1,2
PRACTICE
AID
Access the activity,“Integrating BTK Inhibitors Into the Management of B-Cell Malignancies: How Is Evidence Driving Patient Care?”
at www.peerview.com/XHZ40.
CLINICAL TRIAL LANDSCAPE
This Practice Aid has been provided as a quick reference to help learners apply the information to their daily practice and care of patients.
Ibrutinib Phase 3 Clinical Trials Primary Endpoint(s)
Active, not recruiting Currently recruitingKey:
NCT03112174 (SYMPATICO)
Ibrutinib in combination with venetoclax in patients with MCL
TLS, DLT, PFS
NCT02947347 (PERSPECTIVE)
Ibrutinib with rituximab in patients with treatment-naïve FL
PFS
NCT02443077
Ibrutinib before and after SCT in patients with R/R DLBCL
PFS
NCT03462719 (GLOW/CLL3011)
Ibrutinib + venetoclax vs chlorambucil + obinutuzumab for patients with CLL/SLL (1st line)
PFS
Zanubrutinib (BGB-3111) Phase 3 Clinical Trials Primary Endpoint(s)
NCT03053440
BGB-3111 vs ibrutinib in patients with WM
CR, VGPR
NCT03336333
BGB-3111 vs bendamustine + rituximab in patients with previously untreated CLL/SLL
PFS
NCT01776840 (SHINE)
Ibrutinib in combination with bendamustine + rituximab in patients with newly diagnosed MCL
PFS

4. Selected Studies With BTK Inhibitors
in B-Cell Non-Hodgkin Lymphoma1,2
BTK: Bruton's tyrosine kinase; CLL: chronic lymphocytic leukemia; CR: complete response; DLBCL: diffuse large B-cell lymphoma; DLT: dose-limiting toxicities; FL: follicular lymphoma; MCL: mantle cell lymphoma; MRD- CR: minimal residual disease–negative complete response; NCCN: National Comprehensive
Cancer Network; PFS: progression-free survival; 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 August 20, 2018. 2. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology. B-Cell Lymphomas. Version 4.2018.
PRACTICE
AID
Access the activity,“Integrating BTK Inhibitors Into the Management of B-Cell Malignancies: How Is Evidence Driving Patient Care?”
at www.peerview.com/XHZ40.
CLINICAL TRIAL LANDSCAPE
Acalabrutinib Phase 3 Clinical Trials Primary Endpoint(s)
Active, not recruiting Currently recruitingKey:
NCT02475681 (Elevate CLL TN)
Obinutuzumab + chlorambucil, acalabrutinib + obinutuzumab,
and acalabrutinib in patients with previously untreated CLL
NCT02477696 (Elevate CLL R/R)
Acalabrutinib vs ibrutinib in previously treated patients with high-risk CLL
PFS
NCT02970318 (ACE-CL-309)
Acalabrutinib vs investigator's choice of idelalisib + rituximab
or bendamustine + rituximab in patients with R/R CLL
PFS
NCT02972840 (ACE-LY-308)
Bendamustine + rituximab alone vs in combination with acalabrutinib
in patients with previously untreated MCL
PFS
NCT03516617 [Phase 2]
Acalabrutinib ± obinutuzumab in patients with early-stage CLL/SLL
MRD- CR, time to first therapy
Not yet recruiting
PFS
NCCN Recommendations
NCCN believes that the best management for any patient with cancer is in a clinical trial. Participation in a clinical
trial is especially encouraged.