Long-term findings from the phase 3 Watch & Wait trial show that after a median follow-up of 12.3 years, rituximab is highly effective at delaying time to next treatment in patients with low tumor burden follicular lymphoma (FL). These findings were presented at the 2022 American Society of Hematology (ASH) Annual Meeting by lead author, Michel Northend, MBBS, BSc, MRCP, FRCPath, University College Hospital, London, United Kingdom. 

Watch & Wait is an international phase 3 trial that randomized 463 patients with asymptomatic low tumor burden FL to one of 3 treatment groups: watch and wait approach (n = 187), rituximab induction (n = 84), and rituximab induction followed by rituximab maintenance. The primary end points were time to next treatment (TTNT) and quality of life at 7 months. Secondary end points included response at 25 months, progression-free survival (PFS), overall survival (OS), cause-specific survival (CSS), and rates of spontaneous remission and high-grade transformation.

Previous findings had shown that after a median follow-up of approximately 4 years, 88% of patients receiving rituximab maintenance had not initiated a new treatment at 3 years vs 46% of patients receiving the watch & wait approach. This extended follow-up analysis examined whether this improvement in TTNT was sustained and looked at the time to second next treatment to assess the impact of early use of rituximab in patients who subsequently received rituximab-chemotherapy.

A total of 242 patients initiated new treatment: 133 in the watch and wait arm, 42 in the rituximab induction arm, and 67 in the rituximab maintenance arm. Median TTNT was 2.7 years (95% confidence interval [CI], 2.2 to 4, 9.9 years (95% CI, 5.7 to not reached) and not reached, for each of the arms, respectively.

At 10 years, the percentage of patients who had not started a new treatment was 28.8% (95% CI, 22.1% to 35.8%) in the watch and wait arm, 49.4% (95% CI, 37.4% to 60.3%) in the rituximab induction arm (P <.0001) and 64.5% (95% CI, 56.7% to 71.2%) in the rituximab maintenance arm (P <.0001). Patients in the rituximab maintenance arm experienced significantly longer TTNT than those in the rituximab induction arm (hazard ratio [HR], 0.61; 95% CI, 0.41 to 0.90; P = .012).

In addition, a total 75 patients initiated a second new treatment: 35 patients in the watch and wait arm, 13 patients in the rituximab induction arm, and 27 patients in the rituximab maintenance arm. The median time to second next treatment was not reached in any of the arms.

At 25 months, the overall response rate (ORR) was 52.4% in the rituximab induction arm, with a complete response (CR) of 31%, and 76% in the rituximab maintenance arm, with a CR rate of 63%. 

The 4-year PFS rates were 32.1% (95% CI, 25.5% to 38.9%) with watch and wait, 56.5% (95% CI, 45.2% to 66.4%) with rituximab induction, and 78.4% (95% CI, 71.9% to 83.6%) with rituximab maintenance. PFS in the rituximab maintenance arm was superior to that in the rituximab induction arm (HR, 0.41; 95% CI, 0.27 to 0.65; P <.001). 

The 10-year OS rates were 76.4% in the watch and wait arm, 80.3% in the rituximab induction arm, and 82.5% in the rituximab maintenance arm, with no significant differences reported. The 10-year CSS rates were 87.1%, 87.9% and 89.7%, respectively.

Researchers reported high-grade transformation in 34 (18.2%) patients in the watch and wait arm, 9 (10.7%) patients in the rituximab induction arm and 26 (13.5%) patients in the rituximab maintenance arm. Rates of second primary malignancy were 8.7%, 17.9%, and 15.6%, respectively.

In conclusion, rituximab monotherapy demonstrates high efficacy in delaying TTNT in patients with low tumor burden FL and a strategy utilizing rituximab maintenance is superior to rituximab induction alone. 

“Upfront rituximab should therefore be considered an effective treatment option for patients who wish to delay chemoimmunotherapy,” Dr Northend and colleagues concluded.

Source:

Northend M, Wilson W, Clifton-Hadley L, et al. Long Term Follow-up of International Randomised Phase 3 Study of Rituximab Versus a Watch and Wait Approach for Patients with Asymptomatic, Low Tumour Burden Follicular Lymphoma Shows Rituximab Is Highly Effective at Delaying Time to New Treatment without Detrimental Impact Following Next Line of Therapy. Presented at the ASH Annual Meeting & Exposition; December 10-13, 2022; New Orleans, LA, and virtual. Abstract 607.