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.
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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.
Reference
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
