C021 | IMPACT ON OUTCOMES OF RESPONSE TO HIGH-DOSE METHOTREXAT-BASED INDUCTION AND CONSOLIDATION REGIMEN IN 1,545 PATIENTS WITH PRIMARY CNS LYMPHOMA TREATED WITH AUTOLOGOUS STEM-CELL TRANSPLANTATION IN EBMT CENTERS

Autologous stem cell transplantation (HDC-ASCT) is a valuable consolidation option for PCNSL patients responding to high-dose methotrexate (HD-MTX)-based induction chemoimmunotherapy. The relationship between survival and type of response to induction (CR vs. PR vs. PD), conditioning regimen, and type of induction has not been extensively studied. This study analyses data from first-line induction and consolidation options in PCNSL treated at EBMT centers. A total of 1,545 pts (44% F, 56% M) treated with HD-MTX-based polychemo and HDC-ASCT between 2010 and 2022 recorded in the EBMT registry were analyzed. Median age at ASCT was 59y (range 18-83y); 93 (6%) had a KPS <70. ASCT procedures increased over time: 346 (22%; 2010-2018), 395 (26%; 2018-2020), and 804 (52%; 2020-2022). HD-MTX-based induction included HD-cytarabine in 1,388 (90%) pts, Thiotepa (TT) in 1,018 (66%), and rituximab in 1,264 (82%). Conditioning was TT-based in 1,457 (95%) pts. At the time of ASCT, 773 (50%) pts were in CR, 714 (46%) in PR, and 58 (4%) in PD. By +100 days post ASCT, 995 pts (80%) were in CR and 252 (20%) had residual disease. After a median follow-up of 1.4 years (IQR 1.2-1.6), the 2-y PFS and OS were 75% (95% CI 72-78) and 81% (95% CI 80-83), respectively. No significant difference in OS and PFS was observed between pts who received ASCT in CR or PR, with a 2-y PFS of 76% for both (95% CI 72-79 and 72-80, respectively). Pts diagnosed with PD exhibited worse outcomes but showed a 2-y PFS of 50% (95% CI 33-65). TT-based conditioning regimens improved outcomes (2-y PFS and OS 76% vs. 62%, p=.015, and 82% vs. 63%, p=.002) compared to others. Age at ASCT (HR 1.12, p=.002; HR 1.32, p<.001) and conditioning regimen used (HR 2.24, p<.001; HR 3.24, p=.008) were key factors for OS and NRM. The latter significantly correlated also with PFS. Causes of death (n=215, 14.5%) were lymphoma (n=133), infections (n=20), other transplant-related (n=15), secondary tumors (n=6), and missing (n=41). This is the most extensive series of PCNSL patients treated with consolidative HDC-ASCT in routine practice. Despite the limitations of a registry-based study, such as the lack of image review, this analysis demonstrates that TT-based conditioning regimens were associated with significantly better outcomes and showed similar survival in pts achieving CR and PR at the time of ASCT. Additional investigations are needed to corroborate the beneficial effect of ASCT in some patients with PD after induction.