Early Rituximab Can Delay Need for Chemo in Follicular Lymphoma

Oncology/Hematology
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Lymphoma

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At close to 15 years, 65% of patients on rituximab maintenance required no further treatment

by
Mike Bassett, Staff Writer, MedPage Today
May 5, 2025 • 3 min read

In this open-label trial, a higher proportion of asymptomatic follicular lymphoma patients assigned to rituximab required no further treatment at nearly 15 years compared with those assigned to watchful waiting.About a third of patients in the watchful waiting arm did not require any treatment, suggesting some rituximab patients may have been overtreated.Patients in the study all had advanced-stage, asymptomatic, low tumor burden disease.

Long-term results from a randomized trial confirmed that early rituximab monotherapy for advanced-stage, asymptomatic, low tumor burden follicular lymphoma can substantially delay the need for further treatment.

At nearly 15 years of follow-up, 65% of those assigned to rituximab maintenance and 48% of those given rituximab induction only required no further treatment, as compared with 34% of patients randomized to watchful waiting, reported researchers led by Michael Northend, MBBS, of University College London Hospitals.

The primary outcome of time to next treatment (TTNT) was not yet reached (95% CI 15.6-not estimable) in the maintenance group, 14.8 years (95% CI 7.5-not reached) in the induction group, and 5.6 years (95% CI 3.8-8.4) in the watchful waiting group, they stated in Lancet Haematology.

Thus, patients in the rituximab induction and maintenance groups were significantly less likely to start new treatment versus those in the watchful waiting group:

Induction: HR 0.55 (95% CI 0.38-0.80)Maintenance: HR 0.36 (95% CI 0.26-0.50)
“Our study shows that early rituximab monotherapy further delays the need for chemotherapy with little associated toxicity and no detrimental effect on time to second new treatment,” the researchers said.

Considering the median age at diagnosis is over 65 in follicular lymphoma, “these updated data suggest that early rituximab monotherapy could increase the proportion of patients who never require chemotherapy,” they observed, adding that the optimal treatment approach should take into account individual patient preference and fitness for subsequent chemotherapy.

In an accompanying comment, Eva Kimby, MD, PhD, of the Karolinska Institute in Huddinge, Sweden, said this long-term study follow-up “strengthens the evidence for early rituximab as an option, with the main aim of delaying or avoiding the use of chemotherapy.”

However, she also noted that more than 30% of patients in the watchful waiting group never required treatment, suggesting that many patients will be overtreated with rituximab.

“This, combined with the absence of any benefit of rituximab regarding overall survival and no significant reduction of the risk of high-grade transformation, makes watchful waiting still a valid option,” Kimby said.

Overall survival at 15 years was 73% for the rituximab maintenance group, 66% for the induction group, and 68% for the watchful waiting group, with no significant differences between groups.

Northend and colleagues said they hoped future biological studies will define the factors associated with prolonged treatment-free survival in order to identify patients who won’t benefit from early rituximab.

From October 2004 to May 2009, the phase III trial enrolled adult patients at 118 centers in the U.K., Australia, New Zealand, Turkey, and Poland.

Eligible patients had an Eastern Cooperative Oncology Group (ECOG) 0-1 performance status and were within 3 months of diagnosis of grade 1-3a, stage II–IV, previously untreated follicular lymphoma, with no B symptoms or severe pruritus.

Of the 455 patients randomized (median age around 60; majority female; most ECOG 0), 183 were assigned to watchful waiting (observation until treatment was required), 82 to rituximab induction alone, and 190 to rituximab induction followed by rituximab maintenance. Inclusion in the induction only group was stopped early due to slow accrual to the trial.

The study did find an interaction between sex and treatment. Both groups benefited from early rituximab monotherapy, but women had shorter TTNT with watchful waiting and longer TTNT with rituximab maintenance, suggesting women derived more benefit from early rituximab monotherapy.

Adverse events related to rituximab included five grade 3 infections in the maintenance group, three grade 3 allergies across the two rituximab groups, and four episodes of grade 3/4 neutropenia in the maintenance group.

Second primary malignancies occurred in 20% of patients — 23% of those in the watchful waiting group, 21% in the rituximab induction group, and 16% in the maintenance group — with no significant differences between groups.

Study limitations, according to the researchers, included a lack of long-term toxicity data and the early closure of the rituximab induction group, which limited the ability to compare the induction and maintenance groups.

Mike Bassett is a staff writer focusing on oncology and hematology. He is based in Massachusetts.

Disclosures

The study was funded by Cancer Research UK, Lymphoma Research Trust, Lymphoma Association, and Roche.

Northend disclosed no relationships with industry. Co-authors disclosed relationships with Roche/Genentech, Takeda, Gilead, Sobi, AbbVie, Amgen, GSK, Novartis, Pfizer, Janssen, AstraZeneca, Celgene, Acerta, MEI Pharma, MorphoSys, Sunesis, Bristol Myers Squibb, and the UCLH NIHR Biomedical Research Centre.

Kimby disclosed relationships with Pierre Fabre, AbbVie, AstraZeneca, BeiGene, and Johnson & Johnson.

Primary Source

Lancet Haematology

Source Reference: Northend M, et al “Early rituximab monotherapy versus watchful waiting for advanced stage, asymptomatic, low tumour burden follicular lymphoma: long-term results of a randomised, phase 3 trial” Lancet Haematol 2025; DOI: 10.1016/S2352-3026(25)00034-1.

Secondary Source

Lancet Haematology

Source Reference: Kimby E “Rituximab versus active surveillance in patients with follicular lymphoma” Lancet Haematol 2025; DOI: 10.1016/S2352-3026(25)00105-X.