Introduction: Mediastinal gray zone lymphoma (MGZL) is a rare lymphoma with features intermediate between classical Hodgkin lymphoma (cHL) and diffuse large B cell lymphoma (DLBCL). Due to its rarity and the heterogeneity of its biology, there is a lack of consensus on first line treatment as well as treatment in the setting of relapse or refractory (R/R) disease.

Methods: A retrospective review of adult patients diagnosed with MGZL at University of Kansas Cancer Center between 2012 and 2025 was included. The Kaplan-Meier model was used to evaluate overall survival (OS). OS was determined from date of initial diagnosis to last follow up appointment or date of death. Categorical variables were summarized using frequencies and percentages to provide a comprehensive overview of the dataset.

Results: Ultimately, 20 patients were evaluated. The median age at diagnosis was 35.5 years (20-75), 55% (11/20) were male, 65% (13/20) were white/Caucasian, and 100% had an ECOG PS scale of 0-1. 60% (12/20) had mediastinal involvement, 10% (2/10) had bone marrow involvement, 55% (11/20) had B symptoms, 55% (11/20) had extra-nodal involvement, 35% (7/20) had a ki67 >40%, 40% (8/20) had an elevated LDH, and 75% (15/20) were stage 3-4 at diagnosis. The median follow up was 84 months (95% CI 62.1- 105.9). The median lines of therapy were 2, and the mean was 2.5 (1-9). First line therapy consisted of 50% (10/20) with dose adjusted EPOCH based therapy, 35% (7/20) with CHOP based therapy, 10% (2/20) with AVD based therapy, and 5% (1/20) were other. 35% of patients underwent consolidative radiation. 58% were in complete remission (CR) after first line therapy, 16% had progressive disease (PD), and 26% had a partial response (PR). Of the patients that had CR after first line therapy (CR1), 27.2% (3/11) underwent consolidation with BEAM autologous transplant (auto-HCT). All of those who underwent consolidation after CR1 have been in CR since transplant. Of the 8 patients that had CR1 that did not undergo consolidative auto-HCT, 5 had relapse of disease (62.5%).

65% (13/20) had R/R disease (61.5% (8/13) refractory disease; 38.5% (5/13) relapsed disease). 84.6% (11/13) of salvage regimens were ICE based therapy, 1/13 was Pembro- GVD, and 1/13 was R-GemOx. Of the patients who received ICE based therapy 63.6% (7/11) had CR and 36.3% (4/11) had CR. Both the R-Gemox and Pembro-GVD patients were in CR after receiving these therapies. 30.8% of salvage regimens were an immune checkpoint inhibitor (ICI)-chemotherapy combination regimen. Of the patients who received ICI therapy, 1 patient had a grade 2 ICI-related toxicity of auto-immune hepatitis.

All R/R patients that had PR or CR after salvage or second line therapy underwent autoHCT, with 53.8% (7/13) in CR2 prior to auto-HCT and 38.4% (5/13) in PR prior to auto- HCT. Of those who were in CR2 and underwent auto-HCT, 85.7% (6/7) were in CR at last follow up appointment. One patient underwent consolidation with chimeric antigen receptor therapy (CAR-T) with liso-cel and later had relapse of disease. Two patients underwent allogenic stem cell transplant (allo-HCT), with 1 in PR and 1 with refractory disease prior to allo-HCT. The patient with refractory disease that underwent allo-HCT was in CR at last follow up appointment, while the patient in PR that underwent allo-HCT died due to disease progression. Two patients underwent CD19 directed CAR-T therapy with 1 patient who is in CR at last follow up appointment and the other has relapsed.

The total study population estimated 5-year OS was 69% (95% CI 49-96) and 10-year OS was 61% (95% CI 40-92). Of the patients that underwent auto-HCT, the estimated 5-year OS was 82% (95% CI 62-100) and 10-year OS was 82% (95% CI 62-100). The estimated 5- year OS for the patients that underwent allo-HCT was 50% (95% CI 13-100).

Conclusion: MGZL continues to be a challenging lymphoma subtype to treat in the first line and R/R setting. We observed high R/R disease in this single institution retrospective study that required salvage/further lines of therapy. Results suggest that auto-HCT consolidation in CR1 may be beneficial in avoiding future relapse of disease. Auto-HCT in later line appears to be adventitious with this high R/R population resulting in a high survival rate at 5 and 10 years, as well as durable response. As this is a single institution retrospective with a limited data set, further investigation with more institutions would be beneficial.

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2025
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