Modified Newcastle Regimen Improves Survival Despite Central Nervous System Relapse in Monomorphic Epitheliotropic...

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare, aggressive malignancy with a median overall survival (OS) of 7-15 months. The Newcastle regimen, comprising cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), ifosfamide, etoposide, and epirubicin (IVE), and intermediate-dose methotrexate for central nervous system (CNS) prophylaxis, has demonstrated promising outcomes in enteropathy-associated T-cell lymphoma (EATL) but has not been evaluated in MEITL, where the CNS relapse risk informing methotrexate use remains poorly characterized.

In this real-world cohort of 56 patients with MEITL diagnosed from 2002 to 2025, outcomes were compared between those who received the modified Newcastle (mNewcastle) regimen omitting methotrexate (CHOP/IVE) and those treated with CHOP-based chemotherapy. Survival was estimated using the Kaplan-Meier method with multivariable Cox regression, and CNS relapse was analyzed using a competing risks framework.

Of 52 patients receiving systemic chemotherapy, 22 received the mNewcastle regimen and 28 received CHOP-based chemotherapy, with comparable baseline characteristics. With a median follow-up of 50 months, the mNewcastle was associated with significantly longer median progression-free survival (PFS; 14.4 vs. 6.6 months, p = 0.021) and OS (28.7 vs. 11.7 months, p = 0.021). In multivariable analysis, mNewcastle remained an independent predictor of improved PFS (hazard ratio [HR], 0.44; p = 0.020) and showed a trend toward improved OS (HR, 0.51; p = 0.077). The 2-year cumulative incidence of CNS relapse was 12.1% (95% CI, 2.9-21.4).

The mNewcastle regimen may provide superior survival compared with CHOP-based chemotherapy in MEITL, while CNS relapse remains a clinical concern.

Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.