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Glofitamab Plus R-CHOP Induces High Response Rates in NHL, DLBCL
Preliminary findings from a dose-escalating phase 1b study found glofitamab plus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) induces high response rates with minimal cytokinetic release syndrome (CRS) in patients with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) and previously untreated diffuse large B-cell lymphoma (DLBCL). These data were presented at the 2021 American Society of Hematology (ASH) Annual Meeting.
“Over a third of patients with previously untreated DLBCL do not respond to, or relapse after, R-CHOP. Despite recent advances, patients with R/R NHL have limited curative options,” explained Nilanjan Ghosh, MD, PhD, Levine Cancer Institute/Atrium Health, Charlotte, North Carolina, and co-investigators.
Thus, Dr Ghosh aimed to assess the feasibility and safety of glofitamab, a novel T-cell-engaging bispecific antibody, plus R-CHOP in R/R NHL and previously untreated DLBCL. Response rates were assessed by PET-CT. CRS events were graded by ASTCT criteria.
In the first group of the analysis, 31 patients with R/R NHL with a median of 2 prior lines of therapy received increasing glofitamab doses in separate cohorts (70µg, 1800µg, 10mg and 30mg), plus standard R-CHOP for 6 to 8 cycles, each for 21 days. To mitigate CRS risk, R-CHOP or obinutuzumab-based CHOP (G-CHOP) was given during cycle 1 with the goal of tumor debulking. Glofitamab was then given from cycle 2 on. For the 70µg and 1800µg cohorts, glofitamab was given as a fixed-dose from day 8 of cycle 2 onward. For the 10mg and 30mg cohorts, glofitamab was given as a step-up dose to further mitigate CRS risk. Optional glofitamab maintenance was permitted in the dose-escalating phase only every 2 months for <2 years.
In the second group, 4 out of 13 patients with previously untreated DLBCL, who had an ECOG PS score of 0-3, and had Ann Arbor Stage 3/4 disease, received glofitamab 30 mg plus standard R-CHOP for 6 to 8 cycles, each for 21 days. Patients receiving R-CHOP in cycle 1 had glofitamab step-up dosing starting in cycle 2.
For patients in the first group, after a median follow-up of 9 months, the overall response rate (ORR) was 90 percent (n=28) and the complete response rate (CRR) was 77 percent (n=24). The median duration of response was not met. Reported grade ≥3 adverse events (AEs) happened in 28 (90%) of patients, serious AEs in 21 (68%), and CRS in 17 (55%). One patient had a grade 5 AE (COVID-19 pneumonia not related to the study treatment). AEs led to glofitamab dose modifications or interruptions in 2 (6%) patients and withdrawal in 1 (3%) patient. Neurological AEs happened in 20 (65%) patients. Immune effector cell-associated neurotoxicity syndrome (iCANS)-like AEs were uncommon. Neutropenia occurred in 24 (77%) patients.
For patients in the second group, the CRR was 100%. Out of 13 total patients, 1 (8%) had a CRS event after the first 2.5 mg glofitamab dose. Reported grade ≥3 AEs occurred in 8 (62%) patients, and grade ≥3 AEs related to glofitamab happened in 1 (8%) patient only. No AEs led to glofitamab or R-CHOP dose interruptions. Neutropenia occurred in 6 (46%) patients.
“The very low CRS rate and no neurotoxicity in previously untreated DLBCL may render glofitamab particularly suitable for the outpatient setting without the need for hospitalization,” Dr Ghosh et al concluded.
Researchers concluded that glofitamab plus R-CHOP has tolerable safety in R/R NHL and previously untreated DLBCL.—Emily Bader
Ghosh N, Townsend W, Dickinson M, et al. Glofitamab plus R-CHOP induces high response rates with minimal cytokine release syndrome in patients with relapsed/refractory non-Hodgkin lymphoma and previously untreated diffuse large B-cell lymphoma: Preliminary results from a dose-escalation and safety run-in phase Ib study. Presented at: the 2021 ASH Annual Meeting; Dec. 11-14, 2021; Abstract 2479.
