KEY TAKEAWAYS
- The phase 3 trial compared the efficacy of ITMTX and IVMTX in preventing CNS relapse in a specific subset of high-risk DLBCL patients.
- The study reported that there was no statistically significant difference in preventing CNS relapse between ITMTX and IVMTX in newly diagnosed DLBCL patients at high risk for CNS relapse.
In this prospective, open-label, randomized phase III trial, eligibility criteria included newly diagnosed diffuse large B cell lymphoma (DLBCL) patients (pts) with an age between 18 and 80, Eastern Cooperative Oncology Group Performance Status ≤2, and specific risk factors. These risk factors included a high International Prognostic Index (IPI) score, age-adjusted IPI score, elevated serum lactate dehydrogenase, or involvement of high-risk extra-nodal sites. All pts underwent cerebrospinal fluid analysis to confirm that the central nervous system (CNS) was not involved at diagnosis and received a single dose of intrathecal methotrexate (ITMTX) (15mg) before enrollment.
A total of 151 pts were randomly assigned to either ITMTX or intravenous methotrexate (IVMTX) in addition to the standard RCHOP21 treatment for 6 cycles. In the ITMTX arm, ITMTX was administered during the second to fourth cycles of RCHOP, while in the IVMTX arm, IVMTX was administered during the second and sixth cycles. The study’s primary endpoint was the cumulative incidence of CNS relapse at 2 years after treatment completion, with data cutoff on December 31, 2022.
Of the initial 151 pts, 142 were included in the analysis (ITMTX, n=73; IVMTX, n=69). The reasons for excluding 9 pts included confirmed CNS involvement at diagnosis, consent withdrawal before CNS prophylaxis, and investigator decision. The median age was 63 years in both groups, and baseline characteristics were similar. Most pts completed all six cycles of RCHOP, with no significant difference in adherence between the two arms.
Adverse events were manageable in both groups. After a median follow-up of 23.6 months, no statistically significant difference in the 2-year cumulative incidence of CNS relapse was found between the ITMTX arm (5.5%) and the IVMTX arm (4.9%), with a p-value of 0.749. The median time to CNS relapse was 4.4 months in the ITMTX arm and 12.0 months in the IVMTX arm. The 2-year progression-free survival was similar between the two groups (70.4% in ITMTX vs. 66.4% in IVMTX, p=0.571).
This phase 3 study was the first to compare the prophylactic efficacy of ITMTX and IVMTX in DLBCL. The results indicate no significant difference in preventing CNS relapse between these two treatments in newly diagnosed DLBCL pts at high risk for CNS relapse.
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03123718
Yahng, S., Yhim, H., Kwak, J., Shin, H., Moon, J.H., Eom, H., Kang, K., Park, Y., Kim, M.K., Lee, S.R., Kim, D.S., Kim, H.J., Yi, J.H., Do, Y.R., Kang, H.J., Lim, S., Yang, D.H. PROPHYLACTIC EFFICACY OF INTRATHECAL VERSUS INTRAVENOUS METHOTREXATE FOR CNS RELAPSE IN HIGH-RISK DIFFUSE LARGE B CELL LYMPHOMA : A PHASE III RANDOMIZED, CONTROLLED STUDY. EHA Library. Yahng S. 06/08/2023; 387929; S229
