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

BackgroundSecondary CNS lymphoma is a rare but potentially lethal event in patients with diffuse large B-cell lymphoma. We aimed to assess the activity and safety of an intensive, CNS-directed chemoimmunotherapy consolidated by autologous haematopoietic stem-cell transplantation (HSCT) secondary lymphoma.MethodsThis international, single-arm, phase 2 trial was done 24 hospitals Italy, UK, Netherlands, Switzerland. Adults (aged 18–70 years) histologically diagnosed involvement at time primary diagnosis or relapse Eastern Cooperative Oncology Group Performance Status 3 less were enrolled received three courses MATRix (rituximab 375 mg/m2, intravenous infusion, day 0; methotrexate 3·5 g/m2, first 0·5 g/m2 15 min followed h 1; cytarabine every 12 h, 1 infusions, days 3; thiotepa 30 4) RICE etoposide 100 mg/m2 per 500–1000 mL over 60 1, 2, ifosfamide 5 1000 infusion mesna support, 2; carboplatin area under curve 500 2) carmustine–thiotepa HSCT (carmustine 400 glucose 5% solution 1–2 ?6; mg/kg saline ?5 ?4). The endpoint progression-free survival year. Overall complete response rates before HSCT, duration response, overall survival, endpoints. Analyses modified intention-to-treat population. This study registered ClinicalTrials.gov, NCT02329080. ended after accrual completion; database lock Dec 31, 2019.FindingsBetween March 30, 2015, Aug 3, 2018, 79 enrolled. 75 assessable. 319 (71%) 450 planned delivered. At year from enrolment met, 42 progression free (progression-free 58%; 95% CI 55–61). 49 (65%; 54–76) had objective MATRix–RICE, 29 (39%) whom response. 37 who responded HSCT. end programme, 46 (61%; 51–71) median 26 months (IQR 16–37). follow-up 20–40), 35 33 alive, 2-year 46% (95% 39–53). Grade 3–4 toxicity most commonly haematological: neutropenia (61%) patients, thrombocytopenia 45 (60%), anaemia (35%). serious adverse events recorded (56%) patients; four (5%) those due sepsis caused Gram-negative bacteria (treatment-related mortality 5%; 0·07–9·93).InterpretationMATRix–RICE plus active this population very poor prognosis, acceptable profile.FundingStand Up To Cancer Campaign for Research Swiss foundation, League. Secondary 2019. Between 0·07–9·93). MATRix–RICE profile.