Severe adverse events (AEs) from T-cell-engaging bispecific antibodies are less common in solid tumours than haematological malignancies, new data shows.

The meta-analysis found that less than half of patients with solid tumours experienced grade 3 or worse AEs in clinical trials of the agents, compared to more than 70% of those with blood cancers.

While cytokine release syndrome was the most common treatment-related toxicity of any grade for both cancer types, neutropenia was the most common grade 3 or worse AE in blood cancers, and increased γ-glutamyltransferase in solid tumours.

The data also showed that nearly all patients experienced some kind of AE related to T-cell-engaging bispecific antibodies, while the rate of mortality was 1%, most commonly due to infections, particularly sepsis and opportunistic pathogens.

“These results provide critical evidence to guide clinicians and patients in weighing the therapeutic benefits of T-cell-engaging bispecific antibodies against their safety risks,” wrote the authors.

“By clarifying the adverse event landscape, this study helps close an important gap in the literature and informs the design of safer, more effective treatment strategies,” they added.

The meta-analysis, published in The Lancet Oncology [link here], analysed treatment-related AEs in 104 clinical trials involving 10,353 participants (7,311 with haematological malignancies and 3,042 with solid tumours) and 33 different T-cell-engaging bispecific antibodies.

Across the whole cohort:

• 97.7% of patients experienced at least one treatment-related AE of any grade and 62.5% experienced grade 3 or worse events;
• The pooled incidence of any grade treatment-related AE was 97.5% among haematological malignancy patients and 97.9% in solid tumour patients; and 
• The incidence of grade 3 or above treatment-related AE was 70.3% and 45.3%, respectively.

In haematological malignancies, the most frequent any-grade events were cytokine release syndrome (43.3%), fever or pyrexia (31.1%) and anaemia (22.8%), while the most common grade 3 or worse events were neutropenia (18.1%), infections (12.3%) and anaemia (12.0%).

In solid tumours, cytokine release syndrome (46.3%) was also the most common treatment-related AE of any grade, followed by fever or pyrexia (42.1%) and fatigue (32.2%), while for grade 3 or above events, increased γ-glutamyltransferase (3.7%), lymphopenia (3.5%) and fatigue (3.4%) were most frequent.

Immune effector-cell associated neurotoxicity syndrome was more common in haematological than solid cancers (any grade 9.1% vs 1.3%, grade 3 or above 2.5% vs 0.8%), as were infections (all-grade 22.0% vs 3.0%, grade 3 or above 12.3% vs 1.1%).

Across the whole cohort, 94 deaths were attributed to treatment among 9206 patients (1.0%), with sepsis, pneumonia, neutropenic infection, respiratory failure, septic shock, and multi-organ failure the most frequent causes.

GPRC5D × CD3 constructs were associated with the highest incidence of any-grade or grade 3 or worse AEs in haematological malignancies, while Gp100 × CD3 and survivin-derived peptide × CD3 T-cell-engaging bispecific antibodies caused the highest incidences, respectively, in solid tumours.

“Early identification of T-cell-engaging bispecific antibodies-related symptoms and signs for specific targets is required,” the authors suggested.

“Rash might be an early sign of skin lesions, diarrhoea a sign of colitis, fatigue a sign of anaemia or heart failure, and elevated liver enzymes a sign of hepatitis,” they noted.

“Therefore, when choosing a treatment plan, the side-effects brought by the target information should be taken into account,” they added.