Glofitamab in relapsed/refractory diffuse large B‐cell lymphoma: Real‐world data

Abstract

Glofitamab is a CD3xCD20 bi‐specific antibody with two fragments directed to the CD20 antigen and a single CD3‐binding fragment. Encouraging response and survival rates were recently reported in a pivotal phase II expansion trial conducted in patients with relapsed/refractory (R/R) B‐cell lymphoma. However, the real‐world data of patients of all ages with no strict selection criteria are still lacking. Herein, this retrospective study aimed to evaluate the outcomes of diffuse large B‐cell lymphoma (DLBCL) patients who received glofitamab via compassionate use in Turkey. Forty‐three patients from 20 centers who received at least one dose of the treatment were included in this study. The median age was 54 years. The median number of previous therapies was 4, and 23 patients were refractory to first‐line treatment. Twenty patients had previously undergone autologous stem cell transplantation. The median follow‐up time was 5.7 months. In efficacy‐evaluable patients, 21% and 16% of them achieved complete response and partial response, respectively. The median response duration was 6.3 months. The median progression‐free survival (PFS) and overall survival (OS) was 3.3 and 8.8 months, respectively. None of the treatment‐responsive patients progressed during the study period, and their estimated 1‐year PFS and OS rate was 83%. The most frequently reported toxicity was hematological toxicity. Sixteen patients survived, while 27 died at the time of the analysis. The most common cause of death was disease progression. One patient died of cytokine release syndrome during the first cycle after receiving the first dose of glofitamab. Meanwhile, two patients died due to glofitamab‐related febrile neutropenia. This is the largest real‐world study on the effectiveness and toxicity of glofitamab treatment in R/R DLBCL patients. The median OS of 9 months seems promising in this heavily pretreated group. The toxicity related mortality rates were the primary concerns in this study.

Supportive care measures for bispecific T-cell engager therapies in haematological malignancies

“…Neurotoxicity is infrequently seen with CD20-CD3 TCEs with most agents reporting less than 5% grade ≥ 3 NEs [9–14]. Severe neutropenia of grade ≥ 3 is seen in 20–25% of patients, and rates of grade ≥ 3 infection are reported in around 15–25% [9–14], with similar rates seen in real-world data [14].…”

“…So far, epcoritamab and glofitamab have been approved for the treatment of R/R diffuse large B-cell lymphoma, and mosunetuzumab has been approved for the treatment of R/R follicular lymphoma. CRS is a frequent AE of CD20-CD3 TCEs, occurring in between 15 and 80% of patients depending on the agent, disease context, delivery route, and dose [9][10][11][12][13][14]. Nearly all CRS events are low-grade, confined to the first cycle (with a median onset of less than 1 day from the first dose), and last a median of 2 days with supportive care measures [9][10][11][12][13][14].…”

“…CRS is a frequent AE of CD20-CD3 TCEs, occurring in between 15 and 80% of patients depending on the agent, disease context, delivery route, and dose [9][10][11][12][13][14]. Nearly all CRS events are low-grade, confined to the first cycle (with a median onset of less than 1 day from the first dose), and last a median of 2 days with supportive care measures [9][10][11][12][13][14]. Neurotoxicity is infrequently seen with CD20-CD3 TCEs with most agents reporting less than 5% grade ≥ 3 NEs [9][10][11][12][13][14].…”

“…Nearly all CRS events are low-grade, confined to the first cycle (with a median onset of less than 1 day from the first dose), and last a median of 2 days with supportive care measures [9][10][11][12][13][14]. Neurotoxicity is infrequently seen with CD20-CD3 TCEs with most agents reporting less than 5% grade ≥ 3 NEs [9][10][11][12][13][14]. Severe neutropenia of grade ≥ 3 is seen in 20-25% of patients, and rates of grade ≥ 3 infection are reported in around 15-25% [9-14], with similar rates seen in real-world data [14].…”

B cell responses and antibody‐based therapeutic perspectives in human cancers

“…Similarly, Daratumumab, a monoclonal IgG1 antibody, binds with CD38 on myeloma cells and is extensively used for treating multiple myeloma patients 112 . Resistance to rituximab in relapsed refractory lymphoma patients is common 113 and therefore alternative approaches have been introduced later in the clinical practice, for example targeting CD79b by Polatuzumab 114 or using bi‐specific antibodies, such as Glofitamab which is a CD20‐directed, CD3 T cells engager 115,116 . Trastuzumab, which is also an IgG1 monoclonal antibody, works in a similar fashion to Rituximab or Daratumumab by binding with surface protein Her2 on breast cancer cells and is a life‐saving drug for ER/PR negative Her2 positive breast cancer patients 117 .…”