Loncastuximab Tesirine Demonstrates Promise in Managing Hemophagocytic Lymphohistiocytosis Associated With Diffuse Large B-Cell Lymphoma

Loncastuximab tesirine, in conjunction with standard therapy, demonstrated promise and exhibited favorable activity in patients with secondary malignancy-associated hemophagocytic lymphohistiocytosis (Mal-HLH) driven by diffuse large B-cell lymphoma (DLBCL), according to a case study of 3 patients published in Cureus.¹

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HLH is a severe and rare hyperinflammatory syndrome associated with multiorgan dysfunction and a high rate of mortality. Secondary HLH occurs in adult patients, oftentimes propagated by infection, malignancy, or autoimmune disorders. Incidence of HLH due to malignancy has been reported to be 1% to 2.8% in patients with lymphoma.²

Diagnosing and treating HLH can be challenging since primary and secondary HLH are induced through different mechanisms. The current protocol for treatment recommends early treatment of corticosteroids in pediatric patients. Limited data exists on Mal-HLH, but it is known that the omission of lymphoma-directed therapy has shown a 100% mortality rate in these patients.^1,2

Loncastuximab tesirine, an antibody-drug complex that targets CD19, has previously shown promise in treating DLBCL. The drug is designed to attach itself to CD19, thereby minimizing systemic toxicity and damaging the DNA of lymphoma cells. In the LOTIS-2 trial, approximately 50% of patients who had previously underwent 2 or more treatments showed a complete or partial response to the therapy.³

Prior to the publishing of this study, no literature regarding the treatment of acute Mal-HLH from DLBCL had been published, especially regarding some of the newer agents that have revolutionized the treatment of chemotherapy-refractory DLBCL. Therefore, the investigators reported the experiences of 3 critically ill patients hospitalized with Mal-HLH from DLBCL treated with loncastuximab tesirine.¹

The key outcomes of the trial were ferritin response, defined as greater than 50% reduction, and disease response to loncastuximab tesirine. Patient 1 presented with recurrent Mal-HLH disease progression and was given steroids followed by loncastuximab tesirine. Rapid improvement was observed, though it was unclear what the true peak and onset of ferritin reduction was since the patient’s levels weren’t quantified above 30,000 ng/mL. A complete response was noted 29 days following loncastuximab tesirine, but the patient died due to a separate infection.¹

Regarding patient 2, a diagnosis of Mal-HLH and progression of disease (POD) was confirmed with DLBCL after she presented to the hospital and was transferred to the ICU. On day 36 of treatment with stem cell therapy, the patient was given loncastuximab tesirine; because of the severity of the patient’s condition, multiple HLH-directed therapies were administered. In a positive development, the patient had a 78% reduction from peak ferritin levels 11 days following loncastuximab tesirine treatment, with the onset of decline occurring 1 day after first administration.¹

Patient 3 presented to the hospital with infection after previously documented POD. Despite their admission, POD occurred with new-onset Mal-HLH. Along with HLH-directed therapy, loncastuximab tesirine was administered, but no signs of clinical or laboratory response were noted. Due to refractory Mal-HLH, the patient was transferred to inpatient hospice care.¹

Loncastuximab tesirine was selected for treatment due to multiple theorized advantages, the investigators discussed. Mainly, it was thought to have a more rapid onset than other agents, which was demonstrated in the rapid ferritin response in patients 1 and 2. It was also determined to be an appropriate bridge to CAR-T therapy or allogenic transplant.¹

“While none of the three patients were successfully bridged to potentially curative therapy, we believe loncastuximab tesirine has favorable activity and should be the latest addition in the armamentarium in DLBCL-driven Mal-HLH,” the investigators concluded.¹

REFERENCES

1. Schieber T, Snyder J, Lutfi F, et al. Treatment of secondary hemophagocytic lymphohistiocytosis associated with diffuse large B-cell lymphoma using loncastuximab tesirine as lymphoma-directed therapy. Cureus. 2024;16(9):e70450. doi:10.7759/cureus.70450

2. La Rosée P, Horne A, Hines M, et al. Recommendations for the management of hemophagocytic lymphohistiocytosis in adults. Blood. 2019;133(23):2465-2477. doi:10.1182/blood.2018894618

3. Murphy J. Loncastuximab tesirine shows promise treating diffuse large B-cell lymphoma. Pharmacy Times. Published July 28, 2021. Accessed October 9, 2024. https://www.pharmacytimes.com/view/loncastuximab-tesirine-shows-promise-treating-diffuse-large-b-cell-lymphoma