Nathan H. Fowler, MD, Matthew S. Davids, MD, MMSc, and Sonali M. Smith, MD, prepared useful practice aids pertaining to B-cell malignancies for this CME activity titled "Innovative Therapy in B-Cell Malignancies: An Expert Tumor Board on Novel Agent Classes in CLL, FL, and MCL." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2PZOP99. CME credit will be available until October 8, 2019.

1. Bcl-2: B-cell lymphoma 2; C/A/P: chest/abdominal/pelvic; CBC: complete blood count; CD: cluster of differentiation; chemo: chemotherapy; CT: computed tomography; FL: follicular lymphoma; hep: hepatitis; IHC: immunohistochemistry; LDH: lactate dehydrogenase;
PI3K: phosphatidylinositol-3 kinase; PET: positron emission tomography; PS: performance status; R: rituximab.
1. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology. B-Cell Lymphomas. Version 4.2018. 2. Aliqopa (copanlisib) Prescribing Information. http://labeling.bayerhealthcare.com/html/products/pi/Aliqopa_PI.pdf. Accessed August 14, 2018.
3. Zydelig (idelalisib) Prescribing Information. http://www.gilead.com/~/media/Files/pdfs/medicines/oncology/zydelig/zydelig_pi.pdf. Accessed August 14, 2018. 4. Fowler N et al. 2018 American Society of Clinical Oncology Annual Meeting (ASCO 2018). Abstract 7500.
This Practice Aid has been provided as a quick reference to help learners apply the information to their daily practice and care of patients.
Access the activity,“Innovative Therapy in B-Cell Malignancies: An Expert Tumor Board on Novel Agent Classes in CLL, FL, and MCL,”at www.peerview.com/ZAJ40.
Follicular Lymphoma: Charting
Progress With New Agent Classes
PRACTICE AID
Diagnostic components include
workup, biopsy & hematopathology,
and immunophenotyping1
Essential Immunophenotyping
• IHC panel: CD20, CD3, CD10, Bcl-2,
Bcl-6, CD21, CD23 with/without:
- Cell surface marker analysis:
Kappa/lambda, CD19, CD20,
CD5, CD23, CD10
Essential Workup
• Physical exam, PS, B symptoms, CBC with differential, LDH,
comprehensive metabolic panel, hep B screening, C/A/P CT and/or
whole-body PET/CT, bone marrow biopsy, and pregnancy testing
Lenalidomide + Rituximab4
• Suggested as frontline regimen in untreated FL; recent
phase 3 RELEVANCE trial showed similar efficacy to R-chemo
• Lenalidomide ± rituximab is a preferred regimen for 2L and
subsequent treatment
Obinutuzumab Approved
• In 2L following a rituximab-
containing regimen
• In 1L combined with chemo →
obinutuzumab alone in adult pts
PI3K Inhibitors Approved
• Idelalisib: Relapsed FL in patients
who have received ≥2 prior
systemic therapies
• Copanlisib: Adult patients with
relapsed FL who have received
≥2 prior systemic therapies
Longstanding treatment of FL, particularly in 1L settings, has been based
on rituximab–chemo combinations, although single agent approaches
have been considered for elderly and infirm patients
Recent therapeutic innovations include approval
of next-generation mAbs, PI3K inhibitors,
and phase 3 data on IMiD–mAb regimens1-3
FL

2. Bcl-2: B-cell lymphoma 2; BTK: Bruton tyrosine kinase; CBC: complete blood count; CD: cluster of differentiation; CLL: chronic lymphocytic leukemia; IHC: immunohistochemistry; PS: performance status.
1. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology. Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. Version 1.2019. 2. Imbruvica (ibrutinib) Prescribing Information. https://www.imbruvica.com/docs/librariesprovider7/
default-document-library/prescribing-information.pdf. Accessed August 14, 2018. 3. Gazyva (obinutuzumab) Prescribing Information. https://www.gene.com/download/pdf/gazyva_prescribing.pdf. Accessed August 14, 2018. 4. Venclexta (venetoclax) Prescribing Information.
https://www.rxabbvie.com/pdf/venclexta.pdf. Accessed August 14, 2018. 5. https://clinicaltrials.gov/ct2/show/NCT02048813. Accessed August 21, 2018. 6. https://clinicaltrials.gov/ct2/show/NCT02477696. Accessed August 21, 2018. https://clinicaltrials.gov/ct2/show/
NCT02475681. Accessed August 21, 2018.
This Practice Aid has been provided as a quick reference to help learners apply the information to their daily practice and care of patients.
Chronic Lymphocytic Leukemia: Charting
Progress With New Agent Classes
PRACTICE AID
Access the activity,“Innovative Therapy in B-Cell Malignancies: An Expert Tumor Board on Novel Agent Classes in CLL, FL, and MCL,”at www.peerview.com/ZAJ40.
Diagnostic components include workup,
biopsy & hematopathology, and
immunophenotyping1
Essential Immunophenotyping
• IHC panel: CD3, CD5, CD10, CD20,
CD23, cyclin D1 with/without:
- Cell surface marker analysis:
Kappa/lambda, CD19, CD20,
CD5, CD23, CD10
Essential Workup
• Physical exam including measurement of liver and spleen
size, PS, B symptoms, CBC with differential, and comprehensive
metabolic panel
Bcl-2 Inhibitor Approved
• Venetoclax: for patients with 17p deletion, as detected by an
FDA-approved test, who have received ≥1 prior therapy
Obinutuzumab Approved
• With chlorambucil for previously
untreated CLL
Ibrutinib Approved
• Adult patients with CLL ± 17p
deletion
• Phase 3 study testing ibrutinib
combinations in 1L CLL (E1912)5
Acalabrutinib6,7
• In phase 3 testing (Elevate CLL
trials in 1L and 2L settings)
• Recommended (NCCN 2018) for
relapsed/refractory CLL in frail
older pts (≥65 years) and younger
patients (<65 years)
Historically, treatment of symptomatic CLL was chemotherapy or immunochemotherapy based;
in the past several years, novel agent classes have emerged and established roles as part of CLL care
Recent therapeutic innovations include
approval of next-generation mAbs, BTK
inhibitors, and Bcl-2 inhibitors1-4
CLL

3. BR: bendamustine and rituximab; BTK: Bruton tyrosine kinase; C/A/P: chest/abdominal/pelvic; CD: cluster of differentiation; chemo: chemotherapy; CT: computed tomography; ECG: electrocardiogram; IHC: immunohistochemistry; IMiD: immunomodulatory drug; LDH: lactose
dehydrogenase; MCL: mantle cell lymphoma; MUGA: multiple-gated acquisition; PET: positron emission tomography; PS: performance status; RT: radiation therapy.
1. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology. B-Cell Lymphomas. Version 4.2018. 2. Calquence (acalabrutinib) Prescribing Information. https://www.azpicentral.com/calquence/calquence.pdf#page=1. Accessed August 14, 2018.
3. Revlimid (lenalidomide) Prescribing Information. http://media.celgene.com/content/uploads/revlimid-pi.pdf. Accessed August 14, 2018. 4. https://clinicaltrials.gov/ct2/show/NCT03112174. Accessed August 21, 2018. 5. https://clinicaltrials.gov/ct2/show/NCT02972840. Accessed
August 21, 2018.
This Practice Aid has been provided as a quick reference to help learners apply the information to their daily practice and care of patients.
Mantle Cell Lymphoma: Charting
Progress With New Agent Classes
PRACTICE AID
Access the activity,“Innovative Therapy in B-Cell Malignancies: An Expert Tumor Board on Novel Agent Classes in CLL, FL, and MCL,”at www.peerview.com/ZAJ40.
Diagnostic components include workup,
biopsy & hematopathology, and
immunophenotyping1
Essential Immunophenotyping
• IHC panel: CD20, CD3, CD5, cyclin
D1, CD10, CD21, CD23, BCL2, BCL6,
Ki-67 with/without:
- Cell surface marker analysis:
Kappa/lambda, CD19, CD20,
CD5, CD23, CD10
Essential Workup
• Physical exam, PS, B symptoms, CBC with differential,
comprehensive metabolic panel, LDH, bone marrow biopsy ±
aspirate, C/A/P CT and/or whole-body PET/CT, hep B screening
(if rituximab contemplated), ECG or MUGA scan (if anthracycline or
anthracenedione-based regimen is indicated) and pregnancy testing
(if chemo or RT planned)
IMiD Approved
• Lenalidomide: Relapsed MCL in patients who have received ≥2 prior
systemic therapies, one of which included bortezomib
BTK Inhibitors Approved
• Ibrutinib: Adult patients with
relapsed MCL who have received
≥2 prior systemic therapies
• Ibrutinib–venetoclax combination
is being studied in the phase 3
SIMPATICO trial4
• Acalabrutinib: Adult patients with
relapsed MCL who have received
≥1 prior therapy
• Phase 3 study of 1L acalabrutinib
+ BR is underway5
Immunochemotherapy, often aggressive in nature, is a mainstay of 1L therapy in MCL;
however, relapsed MCL has historically been characterized by poor response rates and overall survival;
newer therapies have emerged in the 2L setting that are more active than traditional tx
Recent therapeutic innovations include
approval of BTK inhibitors and IMiDs1-3
MCL

4. Bcl-2: B-cell lymphoma 2; BID: twice a day; BTK: Bruton tyrosine kinase; C: cycle; CD: cluster of differentiation; cGVHD: chronic graft-versus-host disease; CLL: chronic lymphocytic leukemia; FL: follicular lymphoma; IMiD: immunomodulatory drug; MCL: mantle cell lymphoma;
MZL: marginal zone lymphoma; PI3K: phosphatidylinositol-3 kinase; SLL: small lymphocytic lymphoma; TLS: tumor lysis syndrome; WM: Waldenstrom macroglobulinemia.
1. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology. B-Cell Lymphomas. Version 4.2018. 2. Imbruvica (ibrutinib) Prescribing Information. https://www.imbruvica.com/docs/librariesprovider7/default-document-library/prescribing-
information.pdf. Accessed August 14, 2018. 3. Calquence (acalabrutinib) Prescribing Information. https://www.azpicentral.com/calquence/calquence.pdf#page=1. Accessed August 14, 2018. 4. Zydelig (idelalisib) Prescribing Information. http://www.gilead.com/~/media/Files/
pdfs/medicines/oncology/zydelig/zydelig_pi.pdf. Accessed August 14, 2018. 5. Aliqopa (copanlisib) Prescribing Information. http://labeling.bayerhealthcare.com/html/products/pi/Aliqopa_PI.pdf. Accessed August 14, 2018. 6. Revlimid (lenalidomide) Prescribing Information.
http://media.celgene.com/content/uploads/revlimid-pi.pdf. Accessed August 14, 2018. 7. Gazyva (obinutuzumab) Prescribing Information. https://www.gene.com/download/pdf/gazyva_prescribing.pdf. Accessed August 14, 2018. 8. Venclexta (venetoclax) Prescribing
Information. https://www.rxabbvie.com/pdf/venclexta.pdf. Accessed August 14, 2018.
This Practice Aid has been provided as a quick reference to help learners apply the information to their daily practice and care of patients.
Dosing Guide for Novel Therapies
in FL, CLL, and MCL
PRACTICE AID
Access the activity,“Innovative Therapy in B-Cell Malignancies: An Expert Tumor Board on Novel Agent Classes in CLL, FL, and MCL,”at www.peerview.com/ZAJ40.
Bcl-2 INHIBITOR
Idelasib1,4
• CLL, FL: 150 mg
PO BID
Ibrutinib1,2
• CLL/SLL, WM,
cGVHD: 420 mg PO
daily continuously
until progression of
disease
• MCL, MZL: 560 mg
PO once daily
Copanlisib1,5
• FL: 60 mg
administered as a
1-h IV infusion on d
1, 8, and 15 of a 28-d
treatment cycle on an
intermittent schedule
(3 wk on, 1 wk off)
Lenalidomide1,6
• MCL: 25 mg once
daily orally on d 1-21
of repeated 28-d
cycles
• Renal impairment:
Adjust starting dose
based on clinical and
laboratory findings
• CLL: 100 mg on d 1 +
900 mg on d 2 of C 1
+ 1,000 mg on d 8 +
15 of C 1 + 1,000 mg
on d 1 of C 2-6
• FL: 1,000 mg on d 1, 8,
15 of C 1 + 1,000 mg
on d 1 of C 2-6 or C
2-8, and then 1,000
mg every 2 mo for up
to 2 y
Obinutuzumab1,7
Venetoclax1,8
• CLL: 400 mg PO
daily until disease
progression or
unacceptable toxicity
• Initiate at 20 mg for 1
wk; gradually escalate
to target dose over 5
wk to reduce the risk
of TLS
• Consider re-initiating
at a lower dose, then
continue with dose
escalation in pts who
have tx interruption
for >1 wk during
escalation
Acalabrutinib1,3
• MCL: 100 mg PO
approximately
every 12 hours;
manage toxicities
using treatment
interruption, dose
reduction, or
discontinuation
NEXT-GEN mAbIMiDPI3K INHIBITORSBTK INHIBITORS