98 Follicular Lymphoma Flashcards by Amelie Avenido

TRUE OR FALSE

Follicular lymphoma (FL) is an indolent lymphoid neoplasm that is derived from germinal center (GC) B cells and has a nodular or follicular histologic pattern.

TRUE

Follicular lymphoma (FL) is an indolent lymphoid neoplasm that is derived from germinal center (GC) B cells and has a nodular or follicular histologic pattern.

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The most often cause of patients receiving treatment to fail or relapse within the first 2 years of initiating treatment

20%

Histologic transformation (HT) into diffuse large B-cell lymphoma (DLBCL)

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Median age at diagnosis

63 years

Male-to-female ratio tends to be greater than 1

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Conditions that increase risk for FL

Family history of NHL
Greater body mass index as young adults
Women with Sjögren syndrome
(heavy) smokers (particularly women)
Pesticides

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A genetic hallmark of FL, is detectable in the blood of 50% to 70% of healthy individuals

t(14;18)

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Histologic appearance of FL

Nodular and predominantly follicular pattern
Centroblasts and centrocytes are randomly distributed with a loss of the polarization

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The follicular pattern can be highlighted by CD_ staining (follicular dendritic cell marker).

CD23

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The hallmark of FL and can be useful in distinguishing neoplastic from reactive follicles

BCL2 overexpression

No BCL2 expression is found in 10% to 15% of cases

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FL cells typically express:
* Monoclonal surface immunoglobulin (IgM with or without IgD, IgG, or rarely IgA)
* B-cell associated antigens (CD19, CD20, CD22, and CD79a)
* BCL6 and CD10

but not ___________

CD5 or CD43

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FL Grade 1

0–5 per HPF

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FL Grade 2

6-15 per HPF

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FL Grade 3A

15 centroblasts per HPF; centrocytes still present

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FL Grade 3B

15 centroblasts per HPF; composed only of centroblasts

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Encompass the large majority of the cases (80%)

FL Grade 1 & 2

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A distinct variant of FL differs from nodal FL in that it lacks BCL2 gene rearrangement, and patients usually present with grade 3 disease.

Testicular Follicular Lymphoma

It is reported in children and adolescents but can also occur in adults.
Usually localized, it is associated with a good prognosis after surgery.

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Duodenal-Type Follicular Lymphoma : lesions, usually reported as incidental findings in the ________ portion of the duodenum, present as small polyps.

Second portion of the duodenum

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Similar histology but is BCL2 negative without BCL2, BCL6, IRF4, or any aberrant IG rearrangement

Pediatric Follicular Lymphoma

It usually presents with stage I–II nodal disease, and there is a marked male predominance.

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Detected by immunohistochemistry (IHC) for BCL2, is defined by partial or total colonization of GCs by clonal B cells carrying the t(14;18) in an otherwise reactive lymph node.

In Situ Follicular Neoplasia

Progression to overt FL is infrequent (~5%).

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The most indolent asymptomatic disease not requiring immediate therapeutic intervention occurs in about__________of patients with FL

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One-third

Grade 3B FL is a more aggressive disease requiring DLBCL-like management at diagnosis

FL is an incurable disease except for these 2 conditions:

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(a) localized FL might be cured with nonchemotherapy therapeutic options, and

(b) grade 3B has a low rate of relapse 2 years after immunochemotherapy, suggesting it may be a curable disease, in accord with its similarity to DLBCL

The leading cause of death in patients with FL

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Lymphoma

Especially after disease transformation

Defined by the documentation of an increased number of large cells that eliminate the follicular structure, with a similar microscopic appearance to DLBCL.

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Histologic Transformation

The annual incidence has been estimated at approximately 3%.

TRUE OR FALSE

Patients with de novo HT (ie, a DLBCL histology with pathological findings that favors the existence of the FL component at the time of diagnosis) have a better outcome than those with a transformation event occurring after FL therapy.

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TRUE

Patients with de novo HT (ie, a DLBCL histology with pathological findings that favors the existence of the FL component at the time of diagnosis) have a better outcome than those with a transformation event occurring after FL therapy.

Mutations at diagnosis that might be associated with a shorter time to transformation

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NOTCH2, DTX1, UBE2A, and HISTHIE

The first disease manifestation of FL

Incidental discovery of one or several enlarged lymph nodes ## Footnote Approximately **10% to 20%** of patients with FL present with **B symptoms** (fever, weight loss, night sweats) at diagnosis.

The optimal diagnostic procedure for disgnosis of FL

Surgical removal of an enlarged lymph node ## Footnote The removal of several lymph nodes is not recommended in the context of FL and may expose the patient to surgical sequelae.

# TRUE OR FALSE Most, if not all, cases of FL lesions are FDG avid, and the PET scan is the most sensitive staging procedure.

TRUE Most, if not all, cases of **FL lesions are FDG avid,** and the PET scan is the most sensitive staging procedure.

Diagnostic Criteria that is used to separate FL patients with a low or high tumor burden

Groupe d’Etude des Lymphomes Folliculaires (GELF) and the British National Lymphoma Investigation (BNLI)

# Treatment initiation criteria GELF CRITERIA

Presence of at least one of the following: * Involvement of ≥3 nodal sites, each with a diameter ≥3 cm * Tumor mass ≥7 cm * Symptomatic splenomegaly * Pleural effusion or ascites * Organ compression * Any B symptom * Serum LDH or β2M above upper limit of normal

# Treatment initiation criteria BNLI CRITERIA

Presence of at least one of the following: * Pruritus or B symptom(s) * Rapid generalized disease progression in the preceding 3 months * Life-endangering organ involvement * Significant marrow infiltration * Localized bone lesions detected on radiography or isotope scan * Renal infiltration * “Macroscopic” as opposed to “microscopic” liver involvement.

A more objective measurement of tumor burden

TMTV on the initial PET ## Footnote It has been proposed that a threshold of **510 cm3** could separate patients with a low or high tumor burden, with significant differences in PFS.

Prognostic indices used in FL

Follicular International Prognostic Index (FLIPI) FLIPI2 PRIMA-PI

The **PRIMA PI** is based on two easily available parameters:

β2M and marrow infiltration

Frontline therapy for **Stage I/II Low tumor burden disease**

* “watch and wait,” * radiotherapy (24 Gy) * rituximab (4 weekly infusions) ## Footnote **Immunochemotherapy**, as described later for symptomatic disseminated stages, should be given to patients with stage I disease if they have poor prognosis

Treatment for **Disseminated Follicular Lymphoma Without Treatment Initiation Criteria**

* “watch and wait,” * rituximab (4 weekly infusions)

Treatment for **Disseminated Follicular Lymphoma with Treatment Initiation Criteria**

**Immunochemotherapy** Rituximab was used in combination with chemotherapy (BR, RCHOP, RCVP)

The benefit of **maintenance treatment with rituximab** was demonstrated in what trial

PRIMA trial

Chemotherapy for patients with a **contraindication to anthracyclines**

Chemotherapy for **older patients** given its lower hematologic toxicity

R-CVP

Chemotherapy with efficacy in case of **HT**

R-CHOP

# TRUE OR FALSE Regarding the choice of anti-CD20, obinutuzumab is preferred to rituximab if a longer time before the next treatment is particularly desired.

TRUE Regarding the choice of anti-CD20, **obinutuzumab** is preferred to rituximab if a longer time before the next treatment is particularly desired.

Monitoring during treatment: it is usual to check the tumor response after how many months

**After three or four cycles** of treatment by CT, **at the end of induction**, and **every 6 months** during maintenance ## Footnote **PET results do not influence treatment** in that patients in complete metabolic response (Deauville score 1, 2, or 3) should continue maintenance treatment.

Recommend clinical monitoring for FL patients

Every 3 months in the first year, every 6 months for the next 4 years, and then annually

Recommended imaging for FL patients

**Imaging (CT)** is recommended at **6 months and 1 year after the end of treatment** and then **every 1–2 years**, although the impact of systematic imaging on patient survival is not demonstrated. ## Footnote PET is not recommended for the follow-up of these patients.

Treatment options for Early Relapse or Progression During Initial Treatment ## Footnote Relapses occurring early (ie, within 2 years from treatment initiation) have a **poor prognosis**.

* High-dose chemotherapy followed by a peripheral autologous stem cell transplant (ASCT)* OR * Combination of bendamustine–obinutuzumab followed by maintenance with obinutuzumab ## Footnote *preceded by a platinum– cytarabine-based salvage immunochemotherapy

Treatment options for Late Relapse

* Immunotherapy with four weekly infusions of rituximab at 375 mg/m2* * Immunochemotherapy followed by maintenance treatment with rituximab (every 3 months for 2 years)** * Immunotherapy combination such as lenalidomide and rituximab*** ## Footnote *In cases of progressive disease with low tumor burden or for the most fragile patients **more aggressive disease relapse ***12 cycles of lenalidomide (20 mg/day on days 1–21) plus rituximab once per week for 4 weeks in cycle 1 and day 1 of cycles 2 through 5)

Treatment options for Subsequent Relapses

* Alkylating agents and/or purine analogues * Low-dose radiation therapy (2 × 2 Gy)* * Radioimmunotherapy (ibritumomab tiuxetan or tositumomab)** * PI3K inhibitor (idelalisib, duvelisib, copanlisib) monotherapy*** * * EZH2 inhibitors monotherapy: clinical trial with promising results ## Footnote *localized tumor lesions **more disseminated relapse providing there is not extensive marrow involvement ***previous treatments have included an alkylating agent and rituximab

98 Follicular Lymphoma Flashcards

(47 cards)