Lunsumio
mosunetuzumab-axgb
FDA Approved 2022 3rd Line+ NEW
Approved Indications (US/FDA)
Treatment of adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy.
Dosing Schedule
Step-up IV dosing: Cycle 1 (1mg/2mg/60mg), Cycle 2 (60mg), Cycles 3-17 (30mg)
Cycle Length
Every 21 days for up to 17 cycles
Combination Therapy
Monotherapy (CD20×CD3 bispecific antibody)
Manufacturer
Genentech/Roche
Approval Year
2022
Pivotal Trial
NCT02500407 ↗
Key Publication
Budde et al. Lancet Oncol 2022 ↗
Revlimid
lenalidomide
FDA Approved 2019 2nd Line+ NEW
Approved Indications (US/FDA)
In combination with rituximab for previously treated follicular lymphoma (FL).
Dosing Schedule
20 mg orally once daily on Days 1-21 of each 28-day cycle for up to 12 cycles
Cycle Length
28 days (21 days on, 7 days off)
Combination Therapy
With rituximab 375 mg/m² IV (R² regimen)
Manufacturer
Bristol-Myers Squibb (Celgene)
Approval Year
2019
Pivotal Trial
NCT01938001 ↗
Key Publication
Leonard et al. NEJM 2019 ↗

Overview of Follicular Lymphoma Treatment

Follicular lymphoma is the most common indolent non-Hodgkin lymphoma. Treatment ranges from observation for low-burden disease to anti-CD20-based chemoimmunotherapy. Relapsed/refractory disease has new options including the EZH2 inhibitor tazemetostat, bispecific antibodies (mosunetuzumab), and lenalidomide + rituximab (R² regimen).

Treatment Approach

First-Line

  • Rituximab or obinutuzumab + chemotherapy (GALLIUM)
  • Rituximab + lenalidomide for chemo-free option (RELEVANCE)

Relapsed/Refractory

  • Mosunetuzumab (Lunsumio) — CD20×CD3 bispecific
  • Lenalidomide + rituximab (R²)
  • Tazemetostat (Tazverik) — EZH2 inhibitor

Epidemiology & Impact

Follicular lymphoma is the most common indolent non-Hodgkin lymphoma worldwide, accounting for 20-25% of all NHL diagnoses with approximately 14,500 new cases annually in the United States. Median age at diagnosis is 63 years with equal gender distribution. The clinical course is typically indolent, with median overall survival exceeding 15-20 years. However, approximately 20% of patients experience early progression (POD24) identifying a high-risk subset. Histologic transformation to aggressive DLBCL occurs at 2-3% per year.

Molecular Biology & Biomarkers

The molecular hallmark is the t(14;18)(q32;q21) translocation (approximately 85% of cases), placing BCL-2 under immunoglobulin heavy chain enhancer control and causing resistance to apoptosis. Additional mutations include KMT2D (80-90%), CREBBP (60-65%), and EZH2 (25%, therapeutically targetable with tazemetostat). The FL grading system has prognostic significance, with grade 3B behaving more like DLBCL.

Evolving Treatment Landscape

Treatment has evolved from chemoimmunotherapy toward chemotherapy-free approaches. Lenalidomide plus rituximab (R2) demonstrated non-inferiority to chemoimmunotherapy in the RELEVANCE trial. Mosunetuzumab, a CD20xCD3 bispecific antibody, achieves complete response rates of approximately 60% in relapsed FL. Tazemetostat provides a targeted option for EZH2-mutant FL. CAR-T therapy with axicabtagene ciloleucel is approved for FL after two or more prior lines.

Yescarta
axicabtagene ciloleucel
FDA Approved 2021 3rd Line+ NEW
Approved Indications (US/FDA)
Treatment of adult patients with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy.
Dosing Schedule
Single IV infusion of CAR-T cells (target dose: 2 × 10⁶ CAR-T cells/kg)
Cycle Length
Single infusion following lymphodepleting chemotherapy
Combination Therapy
CD19-directed CAR-T cell therapy (autologous)
Manufacturer
Kite/Gilead
Approval Year
2021
Pivotal Trial
NCT03105336 ↗
Key Publication
Jacobson et al. NEJM 2022 (ZUMA-5) ↗

Approved Therapies