Results from 4 trials presented at the 2022 ASH Annual Meeting may help inform the treatment of newly diagnosed and relapsed/refractory follicular lymphoma (FL).
Long-term follow-up data from a phase 3 trial suggest rituximab induction, with or without rituximab maintenance, can spare FL patients from chemotherapy for 10 years or more.1
A pair of phase 2 trials showed that odronextamab, a bispecific antibody, and tisagenlecleucel, a chimeric antigen receptor (CAR) T-cell therapy, can produce lasting responses in patients with relapsed/refractory FL.2,3
And a phase 1/2 trial showed that a 3-drug combination — polatuzumab vedotin, obinutuzumab, and lenalidomide — can stave off progression for 4 years or more in patients who had relapsed/refractory FL at baseline.4
Rituximab May Allow Freedom From Chemo for 10 Years
The phase 3 Watch & Wait trial showed that rituximab, whether given as induction alone or as both induction and maintenance, significantly prolongs the time to initiation of new treatment (TTNT), compared with the watch-and-wait approach, in patients with FL.1
The trial (ClinicalTrials.gov Identifier: NCT00112931) enrolled 463 patients with asymptomatic, low-tumor-burden FL. At baseline, the median age was 60 years (range, 27-87), 79% of patients had stage III-IV disease, and all had an ECOG performance status of 0-1.
The patients were randomly assigned to watch and wait (n=187), induction with rituximab given at 375 mg/m2 weekly for 4 weeks (n=84), or the same rituximab induction followed by rituximab maintenance at 375 mg/m2, given every 2 months for 12 doses (n=192).
Prior results from this trial showed that, at 3 years, the proportion of patients who did not require new treatment was significantly higher in the rituximab arms than in the watch-and-wait arm.5
At ASH 2022, Michael Northend, MBBS, of University College Hospital in London, UK, presented updated results from this trial, with a median follow-up of 12.7 years.1
The median TTNT was 2.7 years in the watch-and-wait arm, 9.9 years in the rituximab induction arm, and was not reached in the rituximab maintenance arm. At 10 years, the proportion of patients who had not started a new treatment was 28.8% in the watch-and-wait arm, 49.4% in the rituximab induction arm, and 64.1% in the rituximab maintenance arm.
Starting a new treatment was significantly less likely for patients in the rituximab induction arm (hazard ratio [HR], 0.48; 95% CI, 0.34-0.68; P <.001) or the rituximab maintenance arm (HR, 0.31; 95% CI, 0.23-0.42; P <.001), compared with the watch-and-wait arm. The difference between the rituximab arms was also significant (HR, 0.65; 95% CI, 0.44-0.96; P =.03).
The time to initiation of a second new treatment was not reached in any arm. The proportion of patients who had not started a second new treatment at 10 years was 78.0% in the watch-and-wait arm, 85.3% in the rituximab induction arm, and 86.0% in the rituximab maintenance arm.
There was no significant difference in survival outcomes across the arms. The cause-specific survival rate at 10 years was 87.1% in the watch-and-wait arm, 87.9% in the rituximab induction arm, and 89.9% in the rituximab maintenance arm. The overall survival (OS) rates at 10 years were 76.5%, 80.3%, and 82.1%, respectively.
Based on these results, Dr Northend concluded that early treatment with rituximab, either as induction alone or induction and maintenance, should be considered a standard treatment option for patients with asymptomatic, low-tumor-burden FL.
He added, however, that these results also suggest the watch-and-wait approach is still a valid option for this patient population.
“I think it really comes down to patient preference,” he said. “For many patients, the idea of putting off receiving chemotherapy for possibly as much as 10 years or longer would be very attractive …, but for some patients, watch and wait is a really good option. We know some patients who have watch and wait actually never need treatment.”