This document provides a quick reference guide summarizing diagnostic components, essential immunophenotyping, essential workup, and recent therapeutic innovations for several B-cell malignancies including follicular lymphoma, chronic lymphocytic leukemia, mantle cell lymphoma, and diffuse large B-cell lymphoma. It highlights new agent classes such as monoclonal antibodies, PI3K inhibitors, BTK inhibitors, Bcl-2 inhibitors, IMiDs, and CAR-T cell therapies that have established roles in the treatment of these cancers. The summary is intended to help healthcare professionals apply this information to the care of their patients.

1. This Practice Aid has been provided as a quick reference to help learners apply the information to their daily practice and care of patients.
1L: first-line; 2L: second-line; 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; HBV: hepatitis B virus; IHC: immunohistochemistry; IMiD: immunomodulatory imide drugs;
LDH: lactate dehydrogenase; mAb: monoclonal antibodies; PET: positron emission tomography; PI3K: phosphatidylinositol-3 kinase; PS: performance status; R: rituximab; R/R: relapsed/refractory.
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. Morschhauser F et al. N Engl J Med. 2018;379:934-947. 5. Leonard JP et al. 2018 The American Society of Hematology Annual Meeting. Abstract 445.
Access the activity, “Building Innovative Treatment Options for Patients With B-Cell Malignancies: Practical Insights on Clinical Evidence and Integration Strategies,”
at www.peerview.com/HPR40.
PRACTICE AID
Follicular Lymphoma: Charting Progress
With New Agent Classes
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, HBV screening, C/A/P CT and/or whole-body PET/CT, bone
marrow biopsy, and pregnancy testing
Lenalidomide + Rituximab4-5
• 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
• The phase 3 AUGMENT trial showed improvement in PFS in R/R FL with
lenalidomide + rituximab vs rituximab alone
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
and immunophenotyping and phase 3 data on IMiD–mAb regimens
FL

2. 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.
Chronic Lymphocytic Leukemia: Charting
Progress With New Agent Classes
1L: first-line; 2L: second-line; Bcl-2: B-cell lymphoma 2; BTK: Bruton tyrosine kinase; CBC: complete blood count; CD: cluster of differentiation; CLL: chronic lymphocytic leukemia; IHC: immunohistochemistry; mAb: monoclonal antibodies; 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. 7. https://clinicaltrials.gov/ct2/show/
NCT02475681. Accessed August 21, 2018.
Access the activity, “Building Innovative Treatment Options for Patients With B-Cell Malignancies: Practical Insights on Clinical Evidence and Integration Strategies,”
at www.peerview.com/HPR40.
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. 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.
1L: first-line; 2L: second-line; BR: bendamustine and rituximab; BTK: Bruton tyrosine kinase; C/A/P: chest/abdominal/pelvic; CBC: complete blood count; CD: cluster of differentiation; chemo: chemotherapy; CT: computed tomography; ECG: electrocardiogram; HBV: hepatitis B virus;
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; tx: treatment.
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.
Access the activity, “Building Innovative Treatment Options for Patients With B-Cell Malignancies: Practical Insights on Clinical Evidence and Integration Strategies,”
at www.peerview.com/HPR40.
Mantle Cell Lymphoma: Charting
Progress With New Agent Classes
Diagnostic components include workup,
biopsy & hematopathology, and
immunophenotyping1
Essential Immunophenotyping
• IHC panel: CD20, CD3, CD5, cyclin
D1, CD10, CD21, CD23, Bcl-2, Bcl-6,
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, HBV 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
newer therapies have emerged in the 2L setting that are more active than traditional txnewer therapies have emerged in the 2L setting that are more active than traditional tx
MCL

4. 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.
Diffuse Large B-Cell Lymphoma: Charting
Progress With New Agent Classes1
1L: first-line; ASCT: autologous stem cell transplant; Bcl: B-cell lymphoma; BTK: Bruton tyrosine kinase; C/A/P: chest/abdominal/pelvic; CAR-T: chimeric antigen receptor T (cell); CBC: complete blood count; CD: cluster of differentiation; chemo: chemotherapy; DLBCL: diffuse large
B-cell lymphoma; GCB: germinal center B-cell; HBV: hepatitis B virus; HDT: high-dose chemotherapy; IHC: immunohistochemistry; IPI: International Prognostic Index; IRF4: interferon regulatory factor 4; LDH: lactose dehydrogenase; LVF: left ventricle function; MUGA: multigated
acquisition; MUM1: melanoma associated antigen mutated 1; NCCN: National Comprehensive Cancer Network; PS: performance status; R-CHOP: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone; R-EPOCH: rituximab, etoposide phosphate, prednisone,
vincristine, cyclophosphamide, and doxorubicin; R/R: relapsed or refractory; RT: radiation therapy.
1. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology. B-Cell Lymphomas. Version 4.2018.
Access the activity, “Building Innovative Treatment Options for Patients With B-Cell Malignancies: Practical Insights on Clinical Evidence and Integration Strategies,”
at www.peerview.com/HPR40.
Diagnostic components include workup, biopsy
& hematopathology, and immunophenotyping
Essential Immunophenotyping
• IHC panel: CD20, CD3, CD5,
CD10, CD45, Bcl-2, Bcl-6, Ki-67,
IRF4/MUM1, MYC
- Cell surface marker analysis:
Kappa/lambda, CD45, CD3, CD5,
CD19, CD10, CD20
Essential Workup
• Physical exam, PS, B symptoms, CBC with differential, LDH,
comprehensive metabolic panel, uric acid, whole-body PET/CT ± C/A/P CT
with contrast of diagnostic quality, bone marrow biopsy, calculation of IPI, HBV
testing, echocardiogram or MUGA scan (if anthracycline- or anthracenedione-
based regimen indicated), pregnancy testing (if chemo or RT planned)
Approved CAR-T Cell Therapies
• Axicabtagene ciloleucel: Adults with DLBCL after
≥2 prior systemic therapies
• Tisagenlecleucel: Adults with R/R DLBCL after
≥2 prior systemic therapies
Induction Therapy
(Suggestions as per NCCN)
• 1L therapy largely remains R-CHOP
• Other 1L therapies are R-CHOP14
and R-EPOCH
• Anthracycline-sparing
immunochemotherapy for pts with
poor LVF
• Lenalidomide maintenance in pts 60-80 y
of age after R-CHOP
• Modified immunochemotherapy also
available for frail/elderly patients (>80 y
of age) with comorbidities
• Adjusted high-risk IPI: HDT + ASCT
Second-Line and Subsequent Therapy
HDT candidates
• Multi-agent chemotherapy ± rituximab
Non-HDT candidates
• Chemotherapy ± rituximab
• Brentuximab vedotin for CD30+ disease
• Ibrutinib (non-GCB disease)
• Lenalidomide ± rituximab
(non-GCB disease)
Current guidelines, however, suggest the use of novel therapeutics, including
immunomodulating agents and BTK inhibitors; other recent therapeutic innovations include
the approval of CAR-T cell therapy for relapsed/refractory DLBCL
Rituximab-chemotherapy combination remains
the standard of care for previously
untreated DLBCL
DLBCL