Combining consolidative radioimmunotherapy and sequential maintenance rituximab following chemoimmunotherapy improved progression-free survival at 3 years in patients with previously untreated follicular lymphoma, according to findings from the phase II SWOG S0801 study recently published in <em>The Lancet Hematology</em>.
blood cells
Combining consolidative radioimmunotherapy and sequential maintenance rituximab (Rituxan) following chemoimmunotherapy improved progression-free survival (PFS) at 3 years in patients with previously untreated follicular lymphoma, according to findings from the phase II SWOG S0801 study recently published inThe Lancet Hematology.
In the single-arm study, patients received a 5-year treatment plan of consolidative radioimmunotherapy plus sequential maintenance rituximab following R-CHOP chemoimmunotherapy.
“For patients with follicular lymphoma enrolled in our trial, sequential R-CHOP, radioimmunotherapy, and maintenance rituximab resulted in excellent treatment responses and durability of these responses,” the study authors wrote in their published findings.
Treatment consisted of 750 mg/m2of cyclophosphamide, 50 mg/m2of doxorubicin, and 1.4 mg/m2of vincristine intravenously on day 1, with 100 mg of oral prednisone or prednisolone daily for days 1 to 5 plus 375 mg/m2of rituximab on day 1 of cycles 1 to 4. R-CHOP was administered every 21 days for up to 6 cycles. Within 12 weeks after the sixth cycle of R-CHOP, subsequent131iodine tositumomab radioimmunotherapy was given and 375 mg/m2of maintenance rituximab every 3 months for up to 4 years.
Patients had stage III, IV, or bulky stage II follicular lymphoma, grades 1, 2, or 3a. The median age among enrolled patients was 52 (range, 46-60) and 52% were female. The majority (62%) of patients had an ECOG performance status of 0. Twenty-four percent of patients had bulky disease (>10 cm) and 62% had bone marrow involvement. Four-two percent had a high-risk as perceived by a high FLIPI (Follicular Lymphoma International Prognostic Index) score, and 40% had medium risk. Patients were recruited from 20 different institutions within the United States National Cancer Institute Clinical Trials Network.
Of the 84 patients enrolled in the study, 73 completed R-CHOP and radioimmunotherapy treatment. Sixty-nine of the 73 patients received the sequential rituximab maintenance therapy, with 54 patients completing 2 years and 41 patients completing the full 4 years of treatment. Patients were removed from protocol treatment for progressive disease, unacceptable toxicity, or patient preference.
Dose modification of R-CHOP was required in 42% and 9% required dose modification of maintenance rituximab. Maintenance therapy was discontinued in 28 patients.
The primary endpoint of the phase II study was progression-free survival (PFS) after 3 years. Secondary endpoints included PFS after 5 years, overall survival (OS) after 5 years, response rate up to 7 years on protocol or time of disease progression, and safety profile.
The PFS was analyzed in the intention-to-treat population. At 3 years, the PFS was 90% (95% CI, 82%-95%) and 85% at 5 years (95% CI, 75%-91%). OS estimates at 3 years were 96% (95% CI, 89%-99%) and 94% at 5 years (95% CI, 86%-98%). Patients with low or intermediate FLIPI scores tended to have significantly better PFS rates than patients with high FLIPI scores (98% vs 80%, respectively;P= .005).
The most common adverse events of grade 3 or higher during R-CHOP and radioimmunotherapy consolidation were neutropenia (57%), leucopenia (40%), thrombocytopenia (20%), and febrile neutropenia (17%). With maintenance therapy, the most common grade 3/4 adverse event was lymphopenia in 6%. Nine patients had possible treatment-related deaths for secondary or unknown causes in 3 cases, and cirrhosis, cardiac arrest, and secondary malignancies in 1 case each. Secondary malignancies occurred in 7 patients, including 2 sarcomas, 2 colorectal carcinomas, 2 acute myelogenous leukemias, and 1 renal cell carcinoma.
While sequential R-CHOP, consolidative radioimmunotherapy, and maintenance rituximab induced favorable outcomes, the full treatment plan was not followed by a considerable proportion of patients. This suggests that treatment decisions should be made on a case-by-case basis.
The study authors noted that further study is needed to enable clinicians to determine the adequate balance of chemoimmunotherapy and post-induction strategies in patients with follicular lymphoma, “maintenance therapy beyond 2 years and maintenance of any duration following bendamustine might require further study before routine adoption.”
Reference:
Barr PM, Li H, Burack WR, et al. R-CHOP, radioimmunotherapy, and maintenance rituximab in untreated follicular lymphoma (SWOG S0801): a single-arm, phase 2, multicentre study [published online January 24, 2018].Lancet Haematol.doi: 10.1016/S2352-3026(18)30001-2.
Does Odronextamab Show Hope in FL and DLBCL Despite Regulatory Hurdles?
November 5th 2024Despite regulatory challenges from the FDA, odronextamab has received European approval for the treatment of patients with relapsed/refractory follicular lymphoma or diffuse large B-cell lymphoma following 2 prior treatments.
Read More