High-dose sequential chemotherapy and rituximab (R-HDS) supported by autologous stem cell transplantation (ASCT) in patients (pts) with systemic B-cell lymphoma with CNS involvement (SCNSL) at diagnosis or relapse: Interim analysis of feasibility and activity of a phase II trial.

8081 Background: High-dose (HD) chemotherapy supported by ASCT exhibited promising results in a few, small retrospective series of SCNSL. Herein we report the interim analysis of a phase II trial (ClinicalTrials.gov #NCT00801216) addressing a new R-HDS combination with ASCT in these poor-prognosis pts. Methods: Pts (≤65 ys old; ECOG PS 0-3) with SCNSL at diagnosis or relapse were treated with 2 c. of HD-methotrexate + HD-cytarabine (induction); 3 sequential c. of HD-cyclophosphamide, HD-cytarabine, HD-etoposide (R-HDS); BCNU-thiotepa-based conditioning and ASCT. Pts received 6 doses of i.v. rituximab and 4 doses of intrathecal liposomal cytarabine. Pts with CNS residual disease were referred to RT. The 2-year EFS is the primary endpoint (P0 40%; P1 60%; 38 pts required). This approach will be considered active if ≥21 pts will be progression free at 2 yrs. Results: the first 13 registered pts (median age 52 ys, 31-65; M/F ratio 1.6) were analyzed. Six pts were treated at diagnosis; 8 had systemic disease; no pt had positive CSF. Histotypes were diffuse large B-cell (10), mantle cell (2) and follicular (1) lymphomas. Bulky disease (1), ECOG-PS 2-3 (4) and B-symptoms (1) were uncommon; elevated LDH levels were observed in 10 pts. Treatment was completed in 8 pts, is ongoing in 3 (R-HDS), and was interrupted in 2: before conditioning in a poor mobilizer and after the first course due to PD. There were no toxic deaths. G4 neutropenia and thrombocytopenia were reported in all pts, febrile neutropenia in 7, other septic complications in 5. G3-4 non-hematological toxicity was not reported. PBSC collection was successful in 8 of the 9 referred pts (median 9.35 × 109/kg). Nine (69%) pts achieved a CR, 3 a PR (ORR 92%), 1 pt had PD. No pt received RT. At a median f-up of 15 m, 4 pts experienced relapse/PD (CNS 3, extra-CNS 1), with a 2-yr EFS of 46%; 9 pts are alive with a 2-yr OS of 54%. Conclusions: R-HDS supported by ASCT is feasible in pts ≤65 ys old with SCNSL. Preliminary results with this intensive approach are encouraging in this condition, with otherwise dismal prognosis. No significant financial relationships to disclose.