Treatment protocols for follicular lymphoma (FL) are provided below, including general recommendations and an algorithm, treatment by stage, and second-line treatment.
The oncologist managing patients with FL faces several challenges, as controversies do exist regarding the following:
Some clinical scenarios with more straightforward decisions do exist (eg, patients with stage I or II; FL grade 1 or 2 patients with advanced disease [stages III and IV]). Nevertheless, definitions of the best time to initiate therapy continue to divide physicians.
The Groupe d’Etude des Lymphomes Folliculaires (GELF) and the British National Lymphoma Investigation (BNLI) proposed and used defined criteria for patients in whom immediate therapy is necessary.[1, 2]
GELF criteria are as follows[1] :
High tumor bulk is defined with the following parameters:
BNLI criteria are as follows[2] :
Diagnosis of FL involves the following:
Stage I/II
Treatment options are as follows:
Advanced-stage (stages III-IV or bulky stage II) – asymptomatic
Treatment options are as follows:
Advanced-stage (stages III-IV or bulky stage II) – any GELF or BNLI risk factors or high-risk FLIPI score
Treatment options are as follows::
Clinical trial evaluating novel upfront immunochemotherapy approaches with or without postinduction therapy (rituximab maintenance, radioimmunotherapy [RIT], or bone marrow transplantation [BMT]), with correlative science studies
If not on clinical trial: Rituximab plus cyclophosphamide, vincristine, doxorubicin, and prednisone (R-CHOP) or other anthracycline-containing regimens (preferred for FL grade 3) or rituximab plus bendamustine (FL grades 1-2)
Rituximab plus fludarabine or rituximab plus cyclophosphamide, vincristine, and prednisone (CVP); if not eligible for anthracyclines
Relapse
In all cases of relapse, check the following:
For relapse where the duration of remission is at least 1 y, therapeutic options include the following:
For relapse where the duration of remission is < 1 y, therapeutic options include the following:
Stage I or II, World Health Organization (WHO) FL grade 1 or 2[4]
Recommendations are as follows:
First-line treatment recommendations include using rituximab alone, as follows[4] :
Stage III-IV or bulky stage II[4] :
First-line treatment recommendations are as follows:
Rituximab 375 mg/m2 IV weekly for 4 wk with or without four additional doses given every week or every 2 mo (preferred extended schedule of rituximab administration)[5] or
Rituximab and fludarabine[6] : Rituximab 375 mg/m2 IV on day 1 plus fludarabine 25 mg/m2 IV on days 3-5; repeat every 28 d for six cycles (prophylactic trimethoprim-sulfamethoxazole, acyclovir, and fluconazole necessary) or
R-B regimen (rituximab and bendamustine)[7, 8] : Rituximab 375 mg/m2 IV on day 1 plus bendamustine 90 mg/m2 IV on days 1 and 2; repeat every 28 d for six cycles or
R-CHOP regimen[9] : Rituximab 375 mg/m2 IV on day 1 pluscyclophosphamide 750 mg/m2 IV on day 1 or 3 plusdoxorubicin 50 mg/m2 IV on day 1 or 3 plusvincristine 1.4 mg/m2 (dose cap at 2 mg) IV on day 1 or 3 plusprednisone 40 mg/m2 PO on days 1-5 or 3-8; every 21 d for six cycles or
R-CHOP regimen[10] : CHOP chemotherapy (see above) given at 21-d intervals for six cycles in combination with six doses of rituximab 375 mg/m2 IV administered on day 8 (ie, before CHOP) and day 1 of the first cycle of CHOP, on day 1 of cycles three and five of CHOP, and two additional doses on days 28 and 35 after the last cycle of CHOP or
R-CVP regimen[11] : Rituximab 375 mg/m2 IV on day 1 plus cyclophosphamide 750 mg/m2 IV on day 1 plus vincristine 1.4 mg/m2 (dose cap at 2 mg) IV on day 1 plus prednisone 40 mg/m2 PO on days 1-5; every 21 d for six cycles or
R-FND regimen (rituximab, fludarabine, mitoxantrone, and dexamethasone)[12] : Rituximab 375 mg/m2 IV on day 1 plus fludarabine 25 mg/m2 IV on days 1-3 plusmitoxantrone 10 mg/m2 IV on day 1 plus dexamethasone 20 mg PO or IV on days 1-5; every 4 wk for eight cycles (prophylactic trimethoprim-sulfamethoxazole, acyclovir, and fluconazole necessary)
After first-line treatment, the following are recommended:
Treatment options include the following:
Therapeutic options following second-line treatment are as follows:
Obinutuzumab
Obinutuzumab is indicated for FL that is refractory to, or relapses after, a rituximab-containing regimen.[21]
Obinutuzumab is administered with bendamustine for six 28-day cycles:
Duvelisib
Duvelisib is indicated for recurrent or relapsed FL after at least 2 prior systemic therapies[22] :
Mosunetuzumab
Mosunetuzumab is indicated for recurrent or relapsed FL after at least 2 prior systemic therapies[23] :
Tazemetostat
Tazemetostat is indicated for relapsed or refractory FL in patients whose tumors are positive for an EZH2 mutation and who have received at least 2 prior systemic therapies. It is also indicated for relapsed or refractory FL in patients who have no satisfactory alternative treatment options:
Umbralisib
Umbralisib is indicated for relapsed or refractory FL in patients who have received at least 3 prior systemic therapies:
Overview
What is the role of duvelisib in follicular lymphoma (FL) treatment?
What are the areas of controversy regarding the treatment of follicular lymphoma (FL)?
What are the GELF criteria for immediate follicular lymphoma (FL) treatment?
What are the BNLI criteria for immediate follicular lymphoma (FL) treatment?
What is the treatment algorithm for follicular lymphoma (FL)?
How is early-stage follicular lymphoma (FL) treated?
How is advanced-stage follicular lymphoma (FL) treated?
What are the second-line treatment options for follicular lymphoma (FL)?
What are the therapy options for follicular lymphoma (FL) following second-line treatment?
What is the role of obinutuzumab in follicular lymphoma (FL) treatment?