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SAN DIEGO -- The combination of loncastuximab tesirine (Zynlonta) and rituximab achieved promising response rates in patients with relapsed or refractory follicular lymphoma (R/R FL), according to a phase II trial.

The showed that 38 of 39 patients (97%) achieved a response at 12 weeks after treatment, with 26 (67%) achieving a complete response (CR) -- meeting the study's primary endpoint of at least a 50% response at week 12, reported Juan Pablo Alderuccio, MD, of the Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine.

The 6- and 12-month progression-free survival (PFS) rates were both 94.6% (95% CI 79.9-98.6) with median PFS not yet reached. The 6-month overall survival (OS) rate was 97.1% (95% CI 81.4-99.6%), and the 12-month OS rate was 94.1% (95% CI 78.4-98.5), with median OS not yet reached.

The study "suggests that a fixed-duration program of loncastuximab with rituximab is a promising combination in second-line and later follicular lymphoma," Alderuccio said at the American Society of Hematology annual meeting. Results were simultaneously published in .

Alderuccio and colleagues also noted these high response rates were consistent among difficult-to-treat groups, including those with progression or relapse within 24 months (POD24) after the first line of treatment; high-tumour burden, defined by ≥1 Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria; previous transformed FL, and a high-risk FL International Prognostic Index (FLIPI) score:

• POD24: overall response rate (ORR) 100%; CR 85%
• Previously transformed follicular lymphoma: ORR 100%; CR 73%
• ≥1 GELF criteria: ORR 97%; CR 75%
• High-risk FLIPI score: ORR 96%; CR 67%

Response was durable: Among the responders, 22, 10, and five of the patients had their response last at least 12, 18, and 24 months, respectively.

The common treatment-emergent adverse events (TEAEs) were hyperglycemia (44%) and increased alkaline phosphatase (41%), as well as neutropenia, fatigue, and increased aspartate aminotransferase and alanine aminotransferase (38% each).

The most common grade ≥3 TEAEs were lymphopenia in eight patients, and neutropenia in five patients. Sixteen serious TEAEs occurred in 10 patients, with four considered to be related to the study drugs (grade 3 febrile neutropenia, grade 3 dyspnea, grade 3 generalised edema, and grade 3 skin infection).

A TEAE led to treatment discontinuation in one patient.

Study Design

Patients had a histologically confirmed diagnosis of FL that was relapsed or refractory disease after treatment with one or more lines of systemic therapy. They presented with POD24 after the first line of treatment, one or more GELF criteria, or second relapse, and an Eastern Cooperative Oncology Group performance status of 0-2.

Patients in this study had a median age of 68, 54% were male, and 56% were Hispanic. More than half (51.5%) had POD24 and 92% had a high-tumor burden by GELF criteria. Patients had received a median of one prior line of therapy, with 11 (28%) received ≥3 prior lines of therapy.

IV loncastuximab tesirine, a CD19-directed antibody and alkylating agent conjugate, was administered on day 1 of a 21-day cycle, at 0.15 mg/kg for two cycles, then 0.075 mg/kg thereafter. IV rituximab was administered on day 1 of cycle 1, at 375 mg/m² for four once-weekly doses, followed by one dose every 8 weeks on cycles 5, 6, and 7.

At week 21, patients with a CR discontinued loncastuximab tesirine and received two more doses of rituximab once every 8 weeks. Patients with a partial response at week 21 continued both agents for 18 more weeks.

The primary endpoint of a CR rate of at least 50% at week 12 was based on results from the phase III , testing lenalidomide (Revlimid) with rituximab in 358 patients with R/R indolent lymphoma (295 with FL). That trial reported a PFS benefit with the combination (HR 0.46, 95% CI 0.34–0.62, P<0·001) against rituximab alone, and a CR rate of 35% in patients with FL. The lenalidomide-rituximab combination was in 2019 for previously treated FL and marginal zone lymphoma.

Limitations of the current study included the single-center design, lack of a control group, relatively small sample size, and a median follow-up of 18.2 months. Also, the median number of previous lines of therapy was lower than in other "pivotal" studies such as and .

"Acknowledging the need for a randomised clinical trial to inform practice, this study suggests that a fixed-duration and ambulatory regimen of loncastuximab tesirine with rituximab represents a promising combination in the second-line and later treatment of follicular lymphoma, and a is commencing," according to Alderuccio and colleagues.

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