98 Follicular Lymphoma Flashcards
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.
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)
Median age at diagnosis
63 years
Male-to-female ratio tends to be greater than 1
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
A genetic hallmark of FL, is detectable in the blood of 50% to 70% of healthy individuals
t(14;18)
Histologic appearance of FL
Nodular and predominantly follicular pattern
Centroblasts and centrocytes are randomly distributed with a loss of the polarization
The follicular pattern can be highlighted by CD_ staining (follicular dendritic cell marker).
CD23
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
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
FL Grade 1
0–5 per HPF
FL Grade 2
6-15 per HPF
FL Grade 3A
15 centroblasts per HPF; centrocytes still present
FL Grade 3B
15 centroblasts per HPF; composed only of centroblasts
Encompass the large majority of the cases (80%)
FL Grade 1 & 2
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.
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
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.
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%).
The most indolent asymptomatic disease not requiring immediate therapeutic intervention occurs in about__________of patients with FL
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:
(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
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.
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.
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
NOTCH2, DTX1, UBE2A, and HISTHIE
The first disease manifestation of FL
Incidental discovery of one or several enlarged lymph nodes
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
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
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)
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
BR
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
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.
PET is not recommended for the follow-up of these patients.
Treatment options for Early Relapse or Progression During Initial Treatment
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
*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***
*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
localized tumor lesions
**more disseminated relapse providing there is not extensive marrow involvement
**previous treatments have included an alkylating agent and rituximab
