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Sequencing immune-based therapies in B-cell malignancies
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Chimeric antigen receptor (CAR) T-cell therapy can improve outcomes for patients with diffuse large B-cell lymphoma (DLBCL); however, patients with rapid progressive disease at lymphodepletion have poor outcomes.1 The addition of checkpoint inhibitors targeting PD-1 to CAR T-cell therapy may improve outcomes in patients with DLBCL.1
During the 50th Annual Meeting of the EBMT, Amit presented final results from a phase II trial (NCT05385263) investigating the addition of nivolumab, a checkpoint inhibitor targeting PD-1, to CAR T-cell therapy in patients with DLBCL with progressive disease.1 Below, we summarize the key findings.
In the nivolumab group, 50% of patients experienced post-nivolumab cytokine-release syndrome (Table 1).
Table 1. Toxicity profile*
Domain, % |
All patients (n = 20) |
Patients receiving nivolumab (n = 12) |
Patients’ ineligible for nivolumab (n = 8) |
Overall CRS |
85 |
75 |
100 |
Grade 3–4 CRS |
20 |
17 |
25 |
Overall ICANS |
20 |
8 |
38 |
Grade 3–4 ICANS |
10 |
0 |
25 |
Post nivolumab CRS/ICANS |
N/A |
50%† |
N/A |
Grade 3–4 ICAHT |
|||
Early |
15 |
8 |
25 |
Late |
5 |
8 |
0 |
Overall IEC-HS |
10 |
8 |
13 |
Grade 3–4 IEC-HS |
0 |
0 |
0 |
Patients with infections by 3 months |
10 |
17 |
0 |
Patients with IgG <3.5 gr/L |
30 |
33 |
25 |
NRM at 1 month |
5 |
0 |
13 |
CRS, cytokine release syndrome; ICAHT, immune effector cell–associated hematotoxicity; ICANS, immune effector cell associated neurotoxicity syndrome; IEC-HS, immune effector cell–associated hemophagocytic lymphohistiocytosis-like syndrome; IgG, immunoglobulin G; NRM, non-relapse mortality. †All Grade 1–2 CRS. |
Figure 1. 6- and 12-month progression-free survival and overall survival rates*
*Data from Amit1
Key learnings |
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