The FDA approves Loncastuximab for diffuse large B-cell lymphomas


The U.S. Food and Drug Administration granted accelerated approval on April 24 for a new drug for use in patients with relapsed / refractory large B-cell lymphomas (DLBCL) who have tested at least two previous systemic therapies.

The new product, loncastuximab tesirina-lpyl (Zynlonta, ABC Therapeutics), is the first and only conjugate of CD19-targeted antibody drugs approved for this disease.

DLBCL is the most common type of Hodgkin’s lymphoma in the United States, but the indication also includes DLBCL not otherwise specified (NOS), DLBCL derived from a low grade lymphomaand high quality B cell lymphoma.

“There is a significant unmet need for treatment options for patients with [relapsed or refractory] DLBCL, including those who have been heavily pretreated and have difficult-to-treat diseases, “said in a journal Paolo F. Caimi, MD, University Hospitals Cleveland Medical Center and Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio. company press release.

The company also cites data from previous clinical trials that show that more than 40% of first-line DLBCL treatments fail and that these patients have a poor prognosis, getting worse with each line of therapy attempted.

Accelerated approval based on ORR

Accelerated approval was based on the overall response rate (ORR) data of the single-arm LOTIS-2 assay. All patients received the new drug, administered as a 30-minute infusion once every 3 weeks for 1 year.

The trial was performed in 145 patients with DLBCL r / r who had already tried at least two lines of systemic therapy. Caimi noted that this included patients who had been severely pretreated, as the population included patients who had previously received stem cell transplantation or CAR-T cell therapy.

The ORR was 48.3% (70/145 patients), which included a full response rate of 24.1% (35/145 patients) and a partial response rate of 24.1% (35/145 patients). ).

Patients had a mean response time of 1.3 months and the mean response time (mDoR) for the 70 respondents was 10.3 months.

“Continued approval of this indication may depend on the verification and description of the clinical benefit in a confirmatory trial,” the company noted.

There is a phase 3 confirmation process: the LOTIS 5 trial (NCT04384484) compares the combination of loncastuximab tesirin and rituximab vs. chemoimmunotherapy in patients with relapsed / refractory DLBCL.

The company also noted that in a grouped safety population the most common adverse reactions (≥20%) were thrombocytopenia, an increase in liver enzyme levels. gamma-glutamyltransferase (GGT), neutropenia, anemia, hyperglycemia, elevated transaminase, fatigue, hypoalbuminemia, rash, edema, nausea, and musculoskeletal pain.

In the LOTIS-2 trial, the most common emergent adverse events of treatment ≥3 grade ≥3 were neutropenia (26.2%), thrombocytopenia (17.9%), increased GGT (17.2%), and anemia (10.3%).

Permanent discontinuation of treatment as a result of an adverse reaction occurred in 19% of patients, which included an increase in GGT, edema, and effusion.

Dose reductions due to an adverse reaction occurred in 8% of patients, and most were the result of an increase in GGT.

Dose interruptions occurred due to an adverse reaction in 49% of patients, which included an increase in GGT, neutropenia, thrombocytopenia, and edema.

Warnings about effusions, infections and skin reactions

The product warns that severe effusion and edema have been reported. Grade 3 edema occurred in 3% (mainly peripheral edema or ascites), a grade 3 pleural effusion in 3%, and a grade 3 or 4 pericardial effusion in 1%.

Prescribers are advised to monitor patients for new or worsening edema or effusions and to consider diagnostic imaging in patients with symptoms of pleural effusion or pericardial effusion, such as new or worsened dyspnea, chest pain, and / or ascites such as abdominal swelling and inflorescence.

The product also features a warning for serious and fatal infections, including opportunistic infections, and severe skin reactions, including photosensitivity reactions, rashes (including exfoliative and maculopapular) and erythema.

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