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Novel anti-CD47 immunotherapy shows promise in relapsed/refractory lymphoma

Christina Lau
10 Jul 2019

A first-in-class immunoglobulin G4 (IgG4) antibody targeting CD47 has demonstrated durable responses when used in combination with rituximab in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) or indolent lymphoma.

The investigational anti-CD47 immunotherapy, known as Hu5F9-G4 (5F9), was evaluated in 70 patients with R/R DLBCL and 45 patients with R/R indolent lymphoma (including 41 patients with follicular lymphoma [FL] and four patients with marginal zone lymphoma [MZL]) in a phase Ib study and an ongoing phase II study. The results showed rapid and durable responses to the 5F9/rituximab regimen, with most adverse events (AEs) being grade 1/2. [Advani R, et al, EHA 2019, abstract S867]

“Patients [median age, 66 years] in the studies had received a median of three prior therapies, with 85 percent being rituximab-refractory. Results from the phase Ib and phase II cohorts showed a median time to response of 1.8 months among patients who responded to 5F9 at doses up to 45 mg/kg administered in combination with rituximab,” reported investigator Dr Mark Roschewski of the Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, US.

“Median duration of response had not been reached in the phase Ib cohort after a median follow-up of 13.8 months for patients with DLBCL and 21 months for patients with FL,” he continued. “Some patients showed durable complete responses lasting beyond 20 months.”

Among 97 patients from the phase Ib and phase II studies with efficacy data available, an overall response rate (ORR) of 45 percent was reported. The ORR in patients with DLBCL and indolent lymphoma was 36 percent and 61 percent, respectively.

“The complete response [CR] rate was 19 percent overall. In patients with DLBCL and indolent lymphoma, the CR rate was 15 percent and 24 percent, respectively,” said Roschewski.

Treatment-related AEs occurring in >10 percent of patients included infusion reactions (38 percent), headache (34 percent), chills (30 percent), fatigue (30 percent), anaemia (27 percent), nausea (24 percent), pyrexia (23 percent), vomiting (13 percent), and back pain (11 percent).

According to the investigators, the AEs were mostly grade 1/2. Grade 3/4 AEs occurred in no more than 7 percent of patients with the exception of grade 3 anaemia, which was reported in 15 percent of patients and was an expected transient effect occurring with administration of the first dose. Treatment discontinuation due to AEs occurred in 7 percent of the patients.

“Enrolment for the phase II study is ongoing. The 30 mg/kg dose of 5F9 has been selected for further evaluation,” Roschewski noted.

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Most Read Articles
01 Dec 2020
Tetanus toxoid 5 Lf, diphtheria toxoid 2 Lf, pertussis toxoid 2.5 mcg, filamentous haemagglutinin 5 mcg, fimbriae types 2 and 3 5 mcg, pertactin 3 mcg
Dr. Hsu Li Yang, Dr. Tan Thuan Tong, Dr. Andrea Kwa, 08 Jan 2021
Antimicrobial resistance has become increasingly dire as the rapid emergence of drug resistance, especially gram-negative pathogens, has outpaced the development of new antibiotics. At a recent virtual symposium, Dr Hsu Li Yang, Vice Dean (Global Health) and Programme Leader (Infectious Diseases), NUS Saw Swee Hock School of Public Health, presented epidemiological data on multidrug-resistant (MDR) gram-negative bacteria (GNB) in Asia, while Dr Tan Thuan Tong, Head and Senior Consultant, Department of Infectious Diseases, Singapore General Hospital (SGH), focused on the role of ceftazidime-avibactam in MDR GNB infections. Dr Andrea Kwa, Assistant Director of Research, Department of Pharmacy, SGH, joined the panel in an interactive fireside chat, to discuss challenges, practical considerations, and solutions in MDR gram-negative infections. This Pfizer-sponsored symposium was chaired by Dr Ng Shin Yi, Head and Senior Consultant of Surgical Intensive Care, SGH.
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Inhaled corticosteroid (ICS) should be the mainstay of long-term asthma management — such is the key message of the latest Singapore ACE* Clinical Guidance (ACG) for asthma, released in October 2020.
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