Loncastuximab-Rituximab Boosts Response Charges in R/R Follicular Lymphoma

SAN DIEGO — The mixture of loncastuximab tesirine (Zynlonta) and rituximab achieved promising response rates in sufferers with relapsed or refractory follicular lymphoma (R/R FL), in line with a portion II trial.

The single-arm explore confirmed that 38 of 39 sufferers (97%) achieved a response at 12 weeks after medication, with 26 (67%) reaching a complete response (CR) — meeting the explore’s essential endpoint of on the least a 50% response at week 12, reported Juan Pablo Alderuccio, MD, of the Sylvester Entire Cancer Heart on the College of Miami Miller College of Treatment.

The 6- and 12-month development-free survival (PFS) rates have been both 94.6% (95% CI 79.9-98.6) with median PFS no longer yet reached. The 6-month overall survival (OS) payment used to be 97.1% (95% CI 81.4-99.6%), and the 12-month OS payment used to be 94.1% (95% CI 78.4-98.5), with median OS no longer yet reached.

The explore “suggests that a mounted-duration program of loncastuximab with rituximab is a promising mixture in second-line and later follicular lymphoma,” Alderuccio said on the American Society of Hematology annual meeting. Outcomes have been simultaneously printed in Lancet Haematology.

Alderuccio and colleagues moreover eminent these high response rates have been consistent among complicated-to-treat groups, in conjunction with these with development or relapse within 24 months (POD24) after the essential line of medication; high-tumour burden, defined by ≥1 Groupe d’Etude des Lymphomes Folliculaires (GELF) requirements; earlier transformed FL, and a high-possibility FL World Prognostic Index (FLIPI) win:

• POD24: overall response payment (ORR) 100%; CR 85%
• Previously transformed follicular lymphoma: ORR 100%; CR 73%
• ≥1 GELF requirements: ORR 97%; CR 75%
• High-possibility FLIPI win: ORR 96%; CR 67%

Response used to be sturdy: Amongst the responders, 22, 10, and 5 of the sufferers had their response closing on the least 12, 18, and 24 months, respectively.

The everyday medication-emergent adversarial events (TEAEs) have been hyperglycemia (44%) and increased alkaline phosphatase (41%), to boot to neutropenia, fatigue, and increased aspartate aminotransferase and alanine aminotransferase (38% every).

The commonest grade ≥3 TEAEs have been lymphopenia in eight sufferers, and neutropenia in 5 sufferers. Sixteen excessive TEAEs occurred in 10 sufferers, with four belief to be to be associated to the explore pills (grade 3 febrile neutropenia, grade 3 dyspnea, grade 3 generalised edema, and grade 3 skin infection).

A TEAE ended in medication discontinuation in a single patient.

Seek Kind

Sufferers had a histologically confirmed analysis of FL that used to be relapsed or refractory disease after medication with one or more lines of systemic remedy. They offered with POD24 after the essential line of medication, one or more GELF requirements, or second relapse, and an Jap Cooperative Oncology Community performance situation of 0-2.

Sufferers in this explore had a median age of 68, 54% have been male, and 56% have been Hispanic. More than half (51.5%) had POD24 and 92% had a high-tumor burden by GELF requirements. Sufferers had obtained a median of 1 prior line of remedy, with 11 (28%) obtained ≥3 prior lines of remedy.

IV loncastuximab tesirine, a CD19-directed antibody and alkylating agent conjugate, used to be administered on day 1 of a 21-day cycle, at 0.15 mg/kg for 2 cycles, then 0.075 mg/kg thereafter. IV rituximab used to be administered on day 1 of cycle 1, at 375 mg/m² for four as soon as-weekly doses, followed by one dose every 8 weeks on cycles 5, 6, and 7.

At week 21, sufferers with a CR discontinued loncastuximab tesirine and obtained two more doses of rituximab as soon as every 8 weeks. Sufferers with a partial response at week 21 persevered both brokers for 18 more weeks.

The principle endpoint of a CR payment of on the least 50% at week 12 used to be per results from the portion III AUGMENT trial, testing lenalidomide (Revlimid) with rituximab in 358 sufferers with R/R indolent lymphoma (295 with FL). That trial reported a PFS profit with the combo (HR 0.46, 95% CI 0.34–0.62, P<0·001) against rituximab alone, and a CR payment of 35% in sufferers with FL. The lenalidomide-rituximab mixture used to be licensed by the FDA in 2019 for beforehand handled FL and marginal zone lymphoma.

Obstacles of the scorching explore integrated the single-center originate, lack of a preserve an eye on neighborhood, barely small sample dimension, and a median word-up of 18.2 months. Furthermore, the median preference of earlier lines of remedy used to be lower than in assorted “pivotal” stories similar to EPCORE NHL-1 and ZUMA-5.

“Acknowledging the necessity for a randomised clinical trial to expose word, this explore suggests that a mounted-duration and ambulatory routine of loncastuximab tesirine with rituximab represents a promising mixture within the second-line and later medication of follicular lymphoma, and a multicentre expansion cohort is taking off,” in line with Alderuccio and colleagues.