DP068 | ANTI-CD19 CAR-T IS EFFECTIVE IN SECONDARY CENTRAL NERVOUS SYSTEM LYMPHOMA REFRACTORY TO HIGH-DOSE METHOTREXATE-BASED CHEMOTHERAPY

Introduction: Secondary involvement of the CNS is a complication of large B cell lymphomas (LBCL). Treatment of SCNSL differs from systemic lymphomas and is based on high dose chemotherapy (CHT) with drugs that penetrate the blood-brain barrier, HDMTX in particular, followed by autologous stem cell transplantation (ASCT). However, 60% of pts is refractory to or relapses after this treatment. CAR-T is an effective salvage treatment for LBCL but experience in SCNSL is limited to registry studies. Herein we report the management of consecutive pts with SCNSL. Methods: Pts were evaluated for CAR-T eligibility between 07/22 and 03/25. Selected pts were offered a tailored holding therapy and, if in CNS remission after holding, were evaluated for CAR-T eligibility by a multidisciplinary team of experts. Eligible candidates underwent lymphocytoapheresis and bridging therapy until commercial CAR-T infusion. Results: 23 pts were referred to holding: 6 partial-brain irradiation, 4 intrathecal CHT, 2 polatuzumab vedotin, 5 ibrutinib, 1 HD-ifosfamide-based CHT, 2 MATRix regimen, 1 thiotepa-based ASCT, combinations of these strategies in 2. 7 pts experienced progressive disease after holding, were deemed not eligible for CAR-T and died within one month. The other 16 achieved a remission of CNS disease and were eligible for CAR-T (Table). All pts had ECOG 0-1, and all but one were refractory to prior HDMTX. All pts experienced CRS, in only one case G3-4, all CRS cases were successfully treated with tocilizumab and steroids, anakinra was used in 2 cases. ICANS were treated with steroids, plus anakinra in 2 cases. G≥3 ICANS occurs in two pts: one required pre-emptive ICU admission but resolved after 3 days, while the second pt had G1 CRS, developed refractory epilepticus status, and died 18 days after CAR-T infusion. Although recommended washout period was respected, the latter event could be explained by multiple intrathecal CHT instillations performed before CAR-T. Four pts had ≥1 cytopenia at 3 months. At a median follow up of 8 months (IQR: 3-12), 12/16 infused pts remain relapse-free (Figure); 3 had a systemic relapse, while none experienced CNS recurrence. Conclusion: SCNSL refractory to HDMTX-based polyCHT can benefit significantly from a tailored multimodal holding based on the pt’s history and extension of disease. Only pts with good PS and responsive to holding therapy should be offered CAR-T to avoid superfluous toxicity.