The approach also eliminated the need for additional treatments in one-third of patients, and and 36% never needed chemotherapy, significantly reducing their burden of adverse effects.
The study, “Chemotherapy-Free Initial Treatment of Advanced Indolent Lymphoma Has Durable Effect With Low Toxicity: Results From Two Nordic Lymphoma Group Trials With More Than 10 Years of Follow-Up,” was published in the Journal of Clinical Oncology.
Survival rates for indolent lymphomas have significantly improved in recent decades, now reaching a median of approximately 20 years. The combination of chemotherapy and Rituxan is the mainstay first-line treatment for those who exhibit symptoms and have high tumor burden.
However, the optimal timing, sequence, and choice of chemotherapies are still up for debate. Also, with the extended survival of these patients, researchers are looking for options that keep short- and long-term adverse effects to a minimum.
To find out whether a chemotherapy-free regimen would be feasible as first-line treatment for indolent lymphoma patients, researchers in Sweden examined data from two Nordic Lymphoma Group trials with long-term follow-up.
The trials included 321 patients between 1998-1999 and 2002-2008. Most (84%) had follicular lymphoma, and the rest had either marginal zone lymphoma, small lymphocytic lymphoma, or indolent lymphoma not otherwise specified.
Participants received four weekly doses of Rituxan and were eligible for a second four-week round if they responded to the first cycle. Half the patients also received interferon alfa-2a, intended to increase responses to Rituxan.
After a median follow-up of 10 years and seven months, 73% of patients were still alive, which “is at least as good as that observed in modern immunochemotherapy trials,” researchers said.
Survival rates were significantly better among patients who responded to the first cycle of treatment, with 79% of responders living 10 years or more, versus 58% of non-responders. The addition of interferon did not improve survival in the long term.
During this period, 117 patients (36%) never needed chemotherapy, but 24 of these received antibody or radiation therapy.
Among those with indolent lymphoma, disease progression within the first two years of treatment with Rituxan and chemotherapy is predictive of very short survival times.
In the trials, patients who experienced early disease progression after Rituxan treatment were 70% more likely to die during the follow-up, compared to those with late progression. Still, more than half of these patients remained alive for 15 years or more, researchers found.
In 63 patients, the indolent lymphoma transformed into a more aggressive type after a median 4.2 years. This was the first event requiring chemotherapy in half of these patients, and led to a significant drop in median overall survival — only 47% lived past the five-year mark.
Researchers also found that patients with follicular lymphoma had a 90% lower rate of transformation than the remaining patients, even after adjusting for sex and other variables.
Adverse events were few both in the short and long term. Thirty-seven patients developed a second primary cancer, but the rates were similar both in patients who received chemotherapy and those who never needed it.
“Our data indicate that a chemotherapy-free initial approach in patients with indolent lymphoma is associated with an [overall survival] comparable with that found in other studies of first-line immunochemotherapy,” researchers concluded.