Sequential chemoimmunotherapy, radioimmunotherapy, and maintenance treatment with Rituxan (rituximab) improves progression-free survival and delays disease progression in patients with untreated advanced follicular lymphoma, Phase 2 clinical trial data shows.
The study reporting the positive findings of an aggressive therapy approach, “R-CHOP, radioimmunotherapy, and maintenance rituximab in untreated follicular lymphoma (SWOG S0801): a single-arm, phase 2, multicentre study,” was published in the journal The Lancet Hematology.
While several therapeutic options for follicular lymphoma have been developed in the past decades, the ideal sequence or therapeutic combination — and the real benefit of therapies after first-line treatment — remain unclear.
R-CHOP is a standard first-line therapy for advanced follicular lymphoma. It consists of a combination of Rituxan, an engineered anti-CD20 antibody that targets B-cells, and four chemotherapy drugs — cyclophosphamide, doxorubicin, vincristine, and prednisone or prednisolone.
Previous studies have shown that radioimmunotherapy or Rituxan (as maintenance therapy) improved progression free-survival after first-line treatment for follicular lymphoma. But no studies have tested them in combination after initial treatment.
The single-arm, multicenter, Phase 2 clinical trial (NCT00770224) investigated the efficacy and safety of a five-year sequential treatment of R-CHOP, radioimmunotherapy, and Rituxan maintenance.
The treatment plan consisted of R-CHOP every 21 days for up to six cycles, with Rituxan given on day 1 of cycles 1–4, followed by Bexaar (tositumomab) radioimmunotherapy. After that, patients would receive Rituxan every three months for up to four years.
A total of 84 adults (median age 52) were enrolled between April 2009 and December 2010. All patients had advanced follicular lymphoma with no previous treatment, and were being treated at 20 institutions within the National Cancer Institute’s Clinical Trials Network.
R-CHOP and radioimmunotherapy were completed by 73 patients, and of the 69 that moved to the Rituxan maintenance phase, 41 completed the treatment plan.
All patients responded to treatment (irrespective of the therapy phases completed), with about two thirds showing complete responses. At three years, 90 percent of patients were alive and progression-free. At five years, 85 percent remained without disease progression.
“Our findings suggest that this sequential therapeutic regimen is feasible and can further prolong remission duration for patients with follicular lymphoma,” the team wrote.
Researchers also noted that while more than 40 percent of patients had a poor prognosis, only 6 percent progressed in the first two years, “supporting further study of this type of aggressive treatment strategy to prevent early progression.”
The most common severe and very severe adverse events were low levels of neutrophils (neutropenia), a type of white blood cell, low levels of white blood cells, low levels of platelets, and fever with neutropenia.
Seven of 84 patients — or 8 percent — developed a secondary cancer, likely due to radioimmunotherapy. Discontinuation of Rituxan maintenance was mostly due to non-severe recurrent infections and to concerns related to therapy length.
“Additional therapy after induction [first-line treatment] warrants a thorough discussion of risks and benefits, and … treatment decisions should be made on a case-by-case basis,” the researchers wrote.
Tositumomab is currently no longer available, but researchers believe that similar results can be obtained with Zevalin (ibritumomab tiuxetan) as a radioimmunotherapy agent.
“These steps will steer the field toward a precision approach and ultimately enable clinicians to recommend chemoimmunotherapy and post-induction strategies when warranted,” the researchers concluded.