Lymphoplasmacytic Lymphoma Vaccine Leads to Potential Clinical Benefit as Early Intervention

Patients exhibited improved disease-free progression with minimal adverse effects.

Patients with untreated asymptomatic lymphoplasmacytic lymphoma (LPL) who received a first-in-human, neoantigen DNA LPL vaccine achieved stable disease or better with no dose-limiting toxicities experienced, underscoring the potential utilization of this treatment in early-stage disease in patients with LPL, according to results published in Nature Communications.^1,2

Macro Image of Needle Injecting Blue and Purple Cancer Cell

Image credit: © Ishaq | stock.adobe.com

“By doing an early intervention with the vaccine, we nearly doubled the disease-free progression time to an average of just under seven years,” Larry Kwak, MD, PhD, a corresponding author of the trial, said in a news release. “In addition to being effective, the vaccine appears to be safe. It didn’t have any of the harsh side effects associated with other types of common cancer treatments.”⁴

An incurable form of low-grade B-cell lymphoma, LPL is characterized by the presence of clonal lymphoplasmacytic cells that infiltrate the bone marrow as the primary organ and a serum monoclonal protein. Waldenström's macroglobulinemia (WM)—IgM-secreting LPL—is the most common subtype of the disease.³

If there is an absence of end organ damage, patients are deemed to have smoldering phase disease, for which no approved standard therapy exists. Typically, patients are managed by active surveillance and utilizing methods to ease symptoms. The investigators wrote that it would be desirable if a well-tolerated therapeutic agent were available to enable early intervention.^1,3

In this trial, the investigators aimed to examine the efficacy of a DNA LPL vaccine that encodes the autologous LPL-derived Ig single chain variable fragment (scFv) fused to human chemokine CCL20 (macrophage inflammatory protein-3, MIP-3α). The vaccine was designed to trigger T-cell immunity through targeting the delivery of expressed fusion protein to antigen-presenting cells, while linking clinical efficacy with a successful perturbation of the tumor immune microenvironment.¹

A total of 9 patients were enrolled and received a vaccination in the trial. Three patients were in the 500-µg cohort and 6 in the 2500-µg cohort. The median age across the trial was 67, with most of them being male (78%). Lastly, the median time from diagnosis of asymptomatic LPL to a patient’s first immunization was 2.2 years.¹

Determining the vaccine’s maximum tolerated dose (MTD) and its safety profile was of primary importance to the investigators. In a positive development, all patients successfully completed their planned therapy and there were no dose-limiting toxicities or grade 4 adverse events reported.¹

About the Trial

Trial Name: Vaccine Therapy in Treating Patients With Lymphoplasmacytic Lymphoma

ClinicalTrials.gov ID: NCT01209871

Sponsor: MD Anderson Cancer Center

Estimated Study Completion: February 20, 2026

Regarding patient response, 4 patients experienced progression to symptomatic WM, which necessitated the initiation of systemic therapy at 29, 8, 32, and 25 months respectively. One patient, LPL-006, experienced early disease progression and was lost to follow-up 8.8 months following their last vaccination. According to the investigators, the remaining patients are known to be alive.¹

To analyze any vaccine-induced changes that occurred directly in the tumor microenvironment, bone marrow samples were obtained from all patients after a median of 3 months. There was a reduction in clonal tumor subpopulations and their gene-expression pathways following vaccination in the mature B-cell, but not in the LPL plasma cell-like compartment, the investigators found. A paired analysis showed that, overall, there was a reduction in tumor cells in B-cell compartments following vaccination in 6 of the 8 evaluable patients.¹

“As a protoype, our idiotype neoantigen vaccine demonstrated safety, the ability to significantly reduce clonal mature B-cell, but not plasma cell-like, LPL subpopulations and to favorably perturb the tumor microenvironment,” the investigators concluded. “Future functional studies of the pathways affected are needed to confirm the mechanisms of resistance elucidated and to design combination strategies to circumvent them.”¹

REFERENCES

1. Szymura SJ, Wang L, Zhang T, et al. Personalized neoantigen vaccines as early intervention in untreated patients with lymphoplasmacytic lymphoma: a non-randomized phase 1 trial. Nature Comm. 2024;15:6874. doi:10.1038/s41467-024-50880-2

2. ClinicalTrials.gov. Vaccine therapy in treating patients with lymphoplasmacytic lymphoma. National Library of Medicine. Last Updated June 3, 2024. Accessed September 30, 2024. https://clinicaltrials.gov/study/NCT01209871?term=NCT01209871&rank=1

3. Kyle RA, Ansell SA, Kapoor P. Prognostic factors and indications for treatment of Waldenström's Macroglobulinemia. B Pract & Research Clin Haem. 2016;29(2):179-186. doi:10.1016/j.beha.2016.08.014

4. City of Hope. City of Hope vaccine experts report positive results on Phase 1 trial of personalized vaccine for lymphoplasmacytic lymphoma. EurekAlert! News Release. Released September 19, 2024. Accessed September 30, 2024. https://www.eurekalert.org/news-releases/1058570