Lymphodepletion Enhances MAR T-Cell Expansion and Persistence in R/R Lymphoma

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Preconditioning with lymphodepletion was associated with stronger MAR T-cell response and indicative of enhanced antitumor activity in patients with lymphoma who received the MAR T-cell product MT-601 following relapse after CD19-directed CAR T-cell therapy or for whom CAR T-cell therapy is not an option, according to findings from the phase 1 APOLLO trial (NCT05798897).1 

Previously, Marker Therapeutics, the developer of MT-601, had reported that APOLLO patients achieved early objective responses with and without lymphodepletion. However, the most updated findings show preliminary evidence of lymphodepletion supporting the in vivo expansion and persistence of MT-601, which targets 6 tumor-specific antigens.1,2 Using T-cell receptor sequencing as an immunomonitoring strategy, APOLLO investigators found that the expansion and persistence of MAR T-cell clones in MT-601 occurred at significantly higher levels in patients who underwent lymphodepletion vs those who did not. The investigators hypothesize that the robust in vivo expansion and persistence of MT-601 may improve the antitumor activity of the MAR T-cell product in APOLLO.1

“We are excited to see these results from our immunomonitoring study,” Juan Vera, MD, president and chief executive officer of Marker Therapeutics, stated in a news release. “Our preliminary data clearly suggest that lymphodepletion increases the expansion and persistence of MT-601 in patients. This is the first time we have obtained this evidence in vivo, and it provides a clear direction for our MAR-T cell studies going forward.”

Prior studies have demonstrated similar correlations between lymphodepletion and the antitumor activity of other T-cell therapies, such as CAR T-cell and tumor-infiltrating lymphocyte products. Although research suggests that T-cell therapies are effective with or without lymphodepletion, several studies have reported that lymphodepletion enhances the expansion and persistence of T cells and improves clinical outcomes.

Vera noted in the news release that MT-601 continued to have a tolerable safety profile, despite the addition of lymphodepletion. A clinical data readout from APOLLO is expected later in 2025.

The multicenter, open-label APOLLO study is enrolling patients at least 18 years of age with cytologically confirmed non-Hodgkin lymphoma, Hodgkin lymphoma, or chronic lymphocytic leukemia.3 Patients must have measurable disease; a Karnofsky score of at least 70 or an ECOG performance score of 0 or 1; a life expectancy of at least 12 weeks; and adequate blood, liver, renal, and cardiac function. The primary end point of the dose-escalation portion is the safety and tolerability of MT-601, as measured by the number of patients with dose-limiting toxicities (DLTs) and adverse effects. The primary end points of the dose-expansion portion are objective response rate (ORR), duration of response, and complete response (CR) rate. APOLLO trial investigators anticipate the enrollment of up to approximately 30 patients across 9 clinical sites in the United States (US) during the dose-escalation phase of the trial.

Previous data from APOLLO were reported in December 2024.1 At a data cutoff of September 10, 2024, among 9 patients from 5 clinical trial sites across the US, MT-601 infusion was well tolerated in all patients. No DLTs were observed, including no cases of immune effector cell–associated neurotoxicity syndrome. Furthermore, the ORR rate was 78%, and the CR rate was 44.4%; responses were observed as early as 4 weeks following MT-601 infusion.

Following the presentation of these data, the APOLLO trial underwent an increase in patient enrollment, according to the news release. In the first 5 months of 2025, Marker Therapeutics enrolled and successfully manufactured MT-601 for more patients than it did in 2024 as a whole.

“We believe the incorporation of lymphodepletion was the right strategic decision as demonstrated by our immunomonitoring data. The incorporation of lymphodepletion has led to increased T-cell expansion and persistence, which we believe has the potential to further enhance the clinical outcomes we are seeing. We are now enrolling at an increased pace and are well positioned to generate meaningful data, which we expect to share by the end of this summer,” Vera concluded in the news release.

References

1. Marker Therapeutics reports that lymphodepletion improves the expansion and persistence of multi-antigen recognizing T cells in patients with lymphoma. News release. Marker Therapeutics, Inc. May 20, 2025. Accessed May 20, 2025. https://ir.markertherapeutics.com/news-releases/news-release-details/marker-therapeutics-reports-lymphodepletion-improves-expansion
2. Lymphodepletion improves the expansion and persistence of MAR-T cells in patients with lymphoma. Marker Therapeutics. May 20, 2025. Accessed May 20, 2025. https://ir.markertherapeutics.com/static-files/43f99360-d75a-413d-b646-b865e2a7ab47
3. Safety and preliminary efficacy of MT-601 in patients with relapsed/​refractory lymphoma (APOLLO). ClinicalTrials.gov. Updated May 30, 2024. Accessed May 20, 2025. https://clinicaltrials.gov/study/NCT05798897