The final results of the LNH-PRO-05 study showed that a combination of antiproliferative and immunomodulatory agents with chemo had good outcomes in follicular lymphoma patients.
Combination treatment with rituximab, interferon alfa-2b, and dose-dense cyclophosphamide/vincristine/prednisone (CVP) was safe and effective for patients with follicular lymphoma (FL) and an FL International Prognostic Index (FLIPI) score of 2 or greater, according to the final results of the LNH-PRO-05 study published as correspondence in the British Journal of Haematology.
“In the wide and changing therapeutic scenario for FL patients, it is desirable to focus on minimizing both early and long-term toxicity while maintaining efficacy, in order to achieve the long-expected survival,” wrote researchers led by Jimena Cannata-Ortiz, of the Hospital Universitario La Princesca in Madrid. “The use of two antiproliferative and immunomodulatory agents in combination with anthracycline-free chemotherapy can achieve excellent complete response rates in FL patients with a FLIPI score > 2, which translates into excellent progression-free survival (PFS) and overall survival (OS) at 8 years.”
According to the study, 2 decades ago the researchers introduced interferon alfa-2b combined with dose-dense CVP (CVP+IFN) for treatment of FL. Later, data showed a PFS rate of 57% and an OS rate of 79% at 10 years, with patients with a FLIPI score > 2 having worse outcomes.
Once rituximab became available, the researchers began a phase II trial looking only at patients with FLIPI scores of 2 or greater that included rituximab in every cycle of the prior schema (rituximab plus IFN plus CVP).
The study included 50 patients enrolled at 5 centers from 2005 to 2013. About two-thirds (62%) of patients had a FLIPI score of 2 and 38% had a FLIPI score of 3 to 5. Patients were scheduled to receive 8 cycles of therapy with granulocyte colony-stimulating factor support.
All patients were evaluated for response, with 82% achieving complete response at cycle 4 and 100% at cycle 8. With a median follow-up of 6.2 years, the PFS rate was 91% and the OS rate was 98%.
According to the researchers, all of these outcomes were superior to those seen with the prior treatment schema. However, they noted that “the differences might have been overestimated due to the longer follow-up in the former trial.”
The main grade 3/4 toxicity was neutropenia, which occurred in about one-third of patients. Serious adverse events occurred in 8% of cycles, with additional serious adverse events occurring because of delayed neutropenia during follow-up. Additionally, 40% of patients experienced grade 3/4 lymphopenia. No patients died.
“The efficacy/toxicity profile of this treatment stands out as a good option for these patients,” the researchers concluded.
Commenting on these results, Massimo Federico, MD, director of the medical oncology unit at the University of Modena and Reggio Emilia, Italy, said his first reaction was “the more we live, the more we learn.”
According to Federico, the results achieved in patients with advanced and high-risk FL using a combination of three “simple ingredients” such as rituximab, IFN alfa-2b, and dose-dense CVP, were probably beyond even the expectations of the investigators.
“Achieving a complete clinical and molecular response in 100% of cases, in a prospective and multicentric setting is impressive and should represent the basis for additional clinical and biologic studies aimed at better understanding the mechanisms of the extraordinary synergistic effect of three ingredients that, used alone, have demonstrated so far only a limited, although significant, efficacy,” Federico said.