The document outlines essential immunophenotyping and workup procedures for chronic lymphocytic leukemia (CLL), emphasizing the importance of cell surface marker analysis and diagnostic components. It discusses recent therapeutic innovations including various approved agents such as venetoclax, ibrutinib, and acalabrutinib, and their indications and dosing. Additionally, it highlights the role of organizations like the CLL Society in providing education and resources for patients and healthcare providers.

1. Essential Immunophenotyping
• IHC panel: CD3, CD5, CD10, CD20, CD23, and cyclin D1
–
Cell surface marker analysis: kappa/lambda, CD19, CD20, CD5, CD23, and CD10; cytospin for cyclin D1
or FISH for t(11;14); t(11q;v)
Essential Workup1
• Physical exam including measurement of liver and spleen size, PS, B symptoms, CBC with differential,
and comprehensive metabolic panel
Venetoclax (BCL-2 Inhibitor) Approved6
• For adults with CLL
• Preferred upfront and 2L therapy option (plus an anti-CD20 mAb) in older and younger patients with
CLL ± del(17p)/TP53 (NCCN)
Diagnostic components include workup, biopsy and
hematopathology, and immunophenotyping
Recent therapeutic innovations include approval of
next-generation mAbs, BTK inhibitors, and BCL-2 inhibitors1-7
Historically, treatment of symptomatic CLL was chemotherapy or immunochemotherapy; however, in the past
several years, novel agent classes have emerged and established roles in the CLL treatment landscape
CLL Current Status of BCR Inhibitors
• Ibrutinib2
(BTK inhibitor): adults with CLL ± 17p deletion (including as a single agent or in combination
with rituximab or obinutuzumab)
• Acalabrutinib3
(BTK inhibitor): adults with CLL
• Duvelisib4
(PI3K inhibitor): adults with relapsed/refractory CLL after ≥2 prior therapies
• Idelalisib5
(PI3K inhibitor): patients with relapsed CLL, in combination with rituximab, in patients for
whom rituximab alone would be considered appropriate therapy due to other comorbidities
Chronic Lymphocytic Leukemia: Charting
Progress With New Agent Classes
Full abbreviations, accreditation, and disclosure information available at PeerView.com/JWG40
1. NCCN Clinical Practice Guidelines in Oncology: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. Version 4.2020. https://www.nccn.org/professionals/physician_gls/pdf/cll.pdf. 2. Imbruvica (ibrutinib) Prescribing Information. https://www.imbruvica.com/docs/
librariesprovider7/default-document-library/prescribing-information.pdf. 3. Calquence (acalabrutinib) Prescribing Information. https://www.azpicentral.com/calquence/calquence.pdf#page=1. 4. Copiktra (duvelisib) Prescribing Information. http://www.verastem.com/wp-
content/uploads/2018/08/prescribing-information.pdf. 5. Zydelig (idelalisib) Prescribing Information. https://www.gilead.com/~/media/Files/pdfs/medicines/oncology/zydelig/zydelig_pi.pdf. 6. Venclexta (venetoclax) Prescribing Information. https://www.rxabbvie.com/pdf/
venclexta.pdf. 7. Fischer K et al. 57th ASH Annual Meeting and Exposition (ASH 2015). Abstract 496.

2. Acalabrutinib1
Agent
BTKi
• Adult patients with CLL
• In combination with obinutuzumab in patients
with previously untreated CLL
100 mg PO every 12 hours taken with water;
don’t open, break, or chew capsules
CLL Indications Dosing
Ibrutinib2
BTKi
• Adult patients with CLL
• Adult patients with CLL and 17p deletion
• Also approved for use in combination with
obinutuzumab or rituximab in CLL
420 mg PO daily taken with a glass of water;
don’t open, break, or chew the capsules;
don’t cut, crush, or chew the tablets
Note: Dosage differs from use in MCL
Idelalisib4
PI3Ki
• Relapsed CLL in combination with rituximab
• In patients for whom rituximab alone would
be considered appropriate therapy due to
other comorbidities
150 mg PO BID
Duvelisib5
PI3Ki
• Relapsed CLL after ≥2 prior therapies 25 mg PO BID (modify dosage for toxicity)
Venetoclax3
BCL-2i
• Adult patients with CLL
Note: Can be used in combination with obinutuzumab
or rituximab in TN-CLL and R/R CLL, respectively
Take with a meal and water; don’t chew, crush,
or break tablets
• With obinutuzumab:
Initiate venetoclax on day 22
• With rituximab:
Start rituximab after the first
venetoclax cycle and 400 mg
once daily for 7 days
5-week ramp up
Week 1 = 20 mg
Week 2 = 50 mg
Week 3 = 100 mg
Week 4 = 200 mg
Week 5 = 400 mg
Guide for Novel Oral Agents in CLL:
Indications and Dosing
Full abbreviations, accreditation, and disclosure information available at PeerView.com/JWG40
1. Calquence (acalabrutinib) Prescribing Information. https://www.azpicentral.com/calquence/calquence.pdf#page=1. 2. Imbruvica (ibrutinib). Prescribing Information. www.imbruvica.com/docs/librariesprovider7/default-document-library/prescribing-information.pdf.
3. Venclexta (venetoclax) Prescribing Information. https://www.rxabbvie.com/pdf/venclexta.pdf. 4. Zydelig (idelalisib) Prescribing Information. https://www.gilead.com/~/media/Files/pdfs/medicines/oncology/zydelig/zydelig_pi.pdf. 5. Copiktra (duvelisib) Prescribing
Information. https://copiktra.com/pdf/verastem/COPIKTRA-PI-072019.pdf.

3. 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
CLL Society Resources
Full abbreviations, accreditation, and disclosure information available at PeerView.com/JWG40