Treatment of diffuse large B-cell lymphoma (DLBCL) with central nervous system (CNS) involvement with an intensive CNS-directed chemoimmunotherapy regimen followed by autologous hematopoietic stem cell transplant (autoHSCT) was found to be active and had a tolerable safety profile, according to the results of the phase 2 MARIETTA trial (ClinicalTrials.gov Identifier: NCT02329080) published in The Lancet Haematology.
The study authors reported that “…the results of the MARIETTA trial are a step forward in the treatment of secondary CNS lymphoma.”
The international, single-arm trial included 75 patients with DLBCL and CNS involvement, either at diagnosis or relapse, who underwent treatment with 3 courses of rituximab plus methotrexate and thiotepa (MATRix) followed by 3 courses of rituximab plus etoposide and carboplatin (RICE) and carmustine-thiotepa. Patients who achieved a partial or complete response with the MATRix-RICE therapy and showed adequate autologous peripheral blood stem cells underwent autoHSCT. The primary endpoint was 1-year progression-free survival, and secondary endpoints included overall response rate and complete response before autoHSCT, duration of response, overall survival, and safety.
At baseline, the median age was 58 years, and 51% of the patients were men. The International Prognostic Index was high risk in 23% of the patients, intermediate in 35%, low-intermediate in 24%, and low in 19% of the patients assessed.
One-year progression-free survival was 58% (95% CI, 55-61) for the overall cohort and 100% among patients who underwent autoHSCT. Two-year overall survival was 46% (95% CI, 39-53) for the total study population evaluated during a median follow-up of 29 months.
Complete response was found to increase with each component of the regimen. After the second course of MATRix, the complete response rate for systemic and CNS disease was 43% and 35%, respectively, which increased to 55% and 49%, respectively, after MATRix-RICE and 67% and 59%, respectively, after the entire regimen.
The overall response rate for systemic and CNS disease was 75% and 76%, respectively, after 2 courses of MATRix; 75% and 68%, respectively, after MATRix-RICE; and 73% and 61%, respectively, after the entire regimen.
The most common grade 3 to 4 adverse events were hematologic, including neutropenia, thrombocytopenia, and anemia. Treatment-related mortality was 5%, all of which was due to infections.
The authors concluded that “MATRix-RICE plus autologous HSCT was active in this population of patients with very poor prognosis, and had an acceptable toxicity profile.”
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original article for a full list of authors’ affiliations.
Ferreri AJM, Doorduijn JK, Re A, et al. MATRix–RICE therapy and autologous haematopoietic stem-cell transplantation in diffuse large B-cell lymphoma with secondary CNS involvement (MARIETTA): an international, single-arm, phase 2 trial. Lancet Haematol. 2021;8:e110-e121. doi:10.1016/S2352-3026(20)30366-5