Results from a long-term, observational case series in FL: R-CHOP shown to be effective frontline treatment in NHL patients with FLG3

In November 2017, Paolo Strati of the MD Anderson Cancer Center in Houston, Texas and colleagues published online [article in press] in Clinical Lymphoma, Myeloma & Leukemia, a long-term, observational case series of 45 patients with follicular lymphoma grade 3 (FLG3) who had been treated with frontline rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). By closely examining their long-term outcomes, the authors sought to determine an optimal treatment/disease management strategy for this otherwise controversial group of patients.

Key Highlights:

• Largest published case series and longest follow-up of FLG3 treated with frontline R-CHOP
• ORR was 100% and the CR rate 96%, which is similar compared to the original phase II study evaluating the addition of rituximab to CHOP for the treatment of patients with either untreated or relapsing FL, with an ORRs of 100% and a CR rate of 78%
• After median follow-up of 9 years, median PFS has not been reached, and 3-year PFS was 70%

Treatment:

• Patients included in the case series received:
  • Day 0: rituximab 375 mg/m² administered intravenously (IV)
  • Day 1: cyclophosphamide 750 mg/m² IV, doxorubicin 50 mg/m² IV, vincristine 1.4 mg/m² IV (2.0 mg, max.)
  • Days 1-5: prednisone 100 mg/m² daily administered orally
• Treatment cycles were repeated after every 3 weeks for a total of 6 to 8 cycles
  • Median number of administered cycles was 6 (4-8) and 12 (27%) patients received more than 6 cycles
• Radiation therapy (RT) was used as consolidation treatment in some patients at the discretion of the treating physician
  • Twelve (20%) patients had RT as consolidation at the discretion of the treating physician

Efficacy:

• Overall response rate (ORR) was 100%, with 96% of patients achieving complete remission (CR) and 4% of patients achieving partial remission (PR)
• After a median follow-up of 9 years:
  • Median PFS has not been reached and 3-year PFS was 70%
  • Median OS has not been reached, 3-year OS was 98%, and 9 (20%) patients died
• Factors associated with a shorter OS on univariate analysis were age 60 years or older, elevated serum LDH, and elevated serum beta-2 microglobulin level

Safety:

• Anemia (hemoglobin < 12 g/dL), elevated LDH, and elevated beta-2-microglobulin were reported in 18%, 24% and 40% of cases, respectively

While FLG3 represents approximately 30% of FLs and 6% of all lymphomas, some controversy exists that has focused on whether FLG3 should be grouped with DLBCL rather than a discreet grade of FL. The authors had previously published a different iteration of this case series of 45 patients with FLG3 who received frontline R-CHOP at a single institution, which showed a high ORR and improved survival, when compared to a historical group of patients who received CHOP-like regimens that did not include rituximab. They chose to focus on these patients because they are not commonly included in clinical trials or their outcome is often not reported separately. The long-term follow up of these patients has shown, the authors conclude, that R-CHOP is an effective frontline treatment for patients with FLG3, underscored by the 3-year PFS of 70%, in addition to ORR and CR rates of 100% and 96%, respectively.

Abstract 

The optimal management of patients with follicular lymphoma grade 3 (FLG3) is controversial. This is a case series of 45 patients with FLG3 treated with frontline R-CHOP and observed for an extended time interval. The overall response rate was 100% and the median progression-free survival (PFS) has not been reached, with a 3-year PFS of 70%; 14 (31%) patients relapsed, nearly all within 3 years. The baseline characteristic more strongly associated with a shorter PFS were lymph node sites more than 4 and presence of B symptoms. Three patients later progressed to DLBCL, all had baseline elevated serum LDH and high IPI score. Median overall survival (OS) has not been reached. All 4 patients who later developed AML were older than 60 at the time of start of therapy. R-CHOP is an effective frontline treatment for patients with FLG3, and may provide extended PFS, comparable to outcomes observed in diffuse large B-cell lymphoma, particularly in subgroups with limited nodal disease.