Carmelo Carlo-Stella, MD, PhD, Department of Biomedical Sciences, Humanitas University, Department of Oncology and Hematology, IRCCS Humanitas Research Hospital, discusses the FDA approval of glofitamab-gxbm (Columvi) for the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified or large B-cell lymphoma arising from follicular lymphoma, after at least 2 lines of systemic therapy.

The June 15, 2023, approval was based on findings from the phase 1/2 NP30179 trial (NCT03075696), which demonstrated that the CD20xCD3 T-cell–engaging bispecific antibody glofitamab led to a 56% overall response rate (ORR) and a complete response (CR) rate of 43%. Additionally, the median duration of response was 18.4 months (95% CI, 11.4-not estimable) and 68.5% of responders continued to respond for 9 months or longer (95% CI, 56.7-80.3). 

In the study, the agent was administered in 13 intravenous infusions for up to 12 cycles, including step-up dosing, until disease progression or intolerance. Following cycle 1 of treatment, glofitamab was given once every 3 weeks. In terms of safety, the most common adverse effects (AEs; n = 145) were cytokine release syndrome (CRS; 70%), musculoskeletal pain (21%), fatigue (20%), and rash (20%). CRS was mostly low grade, occurring most often at grade 1 (52%) and grade 2 (14%).

The standard of care for patients with relapsed/refractory DLBCL has been cytotoxic chemotherapy, which fails to elicit responses in most patients, Carlo-Stella adds. As such, the approval is a great accomplishment, ridding some patients of large bulky tumors with lymph node involvement in a mere 2 days, Carlo-Stella says. The approval also sets the stage for further development of immunotherapy in this population, Carlo-Stella adds. 

Continued approval for the current indication may be contingent upon the results of a confirmatory trial.

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Carmelo Carlo-Stella, MD, PhD, discusses the FDA approval of glofitamab for the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma not otherwise specified or large B-cell lymphoma arising from follicular lymphoma, after at least 2 lines of systemic therapy.

Dr Carlo-Stella on the FDA Approval of Glofitamab in Relapsed/Refractory DLBCL

Carmelo Carlo-Stella, MD, PhD, Department of Biomedical Sciences, Humanitas University, Department of Oncology and Hematology, IRCCS Humanitas Research Hospital in Rozzano, Italy, discusses the evaluation of subcutaneous and intravenous (IV) RG6234 in relapsed/refractory multiple myeloma.

A phase 1 dose-escalation trial (NCT04557150) evaluated both subcutaneous and IV RG6234 in patients with heavily pretreated multiple myeloma who previously received treatment with an immunomodulatory drug and proteasome inhibitor and are intolerant to or have no other option for standard-of-care treatment.

Updated results presented at the 2022 ASH Annual Meeting showed that patients who received IV RG6234 experienced an overall response rate (ORR) of 71.4%, and those in the subcutaneous RG6234 cohort had an ORR of 63.6%. Notably, 50% of patients in the IV cohort achieved a very good partial response or better. Additionally, 71.4% of patients who achieved complete remission (CR) became minimal residual disease negative.

RG6234 is a GPRC5DxCD3 T-cell engaging bispecific antibody that targets CD3 cells and multiple myeloma plasma cells, Carlo-Stella explains. Upon the antibody aligning with the bindings of the T-cells and myeloma cells, the T-cells are activated, in turn producing cytokines that target myeloma plasma cells, Carlo-Stella says.

Due to their off-the-shelf nature and ease of use, bispecific antibodies have gained more traction across hematologic malignancies in recent years, Carlo-Stella notes, adding that this shift has largely occurred across the landscape of lymphoproliferative disorders. These agents have created high expectations for both physicians and patients, Carlo-Stella emphasizes.

At this stage in development, RG6234 remains under evaluation in a phase 1 clinical trial that has enrolled 108 patients with relapsed/refractory multiple myeloma. Approximately half of these patients have been treated with IV RG6234, and the other half were treated subcutaneously, Carlo-Stella notes. Investigators hope to develop RG6234 as a subcutaneous drug as a fixed-duration therapy, Carlo-Stella concludes.

Carmelo Carlo-Stella, MD, PhD, discusses the evaluation of subcutaneous and intravenous RG6234 in relapsed/refractory multiple myeloma.

Dr. Carlo-Stella on the Investigation of RG6234 in R/R Multiple Myeloma

Carmelo Carlo-Stella, MD, PhD, Department of Biomedical Sciences, Humanitas University, Department of Oncology and Hematology, IRCCS Humanitas Research Hospital, discusses updated results from a phase 1 dose-escalation study (NCT04557150) of subcutaneous (SC) and intravenous (IV) RG6234 in relapsed/refractory multiple myeloma.

The study evaluated the safety and pharmacokinetics of RG6234, a GPRC5DxCD3 T-cell engaging bispecific antibody, in patients with relapsed or refractory multiple myeloma who have no sufficient available or tolerable standard-of-care treatments.

Data presented at the 2022 ASH Annual Meeting demonstrated that RG6234 was highly effective when administered either intravenously or subcutaneously, Carlo-Stella states. The overall response rate (ORR) was 71.4% in the IV cohort and 63.6% in the SC cohort. Notably, over 50% of patients in the IV cohort displayed a very good partial response or better.

Additionally, 71.4% of patients who achieved complete remission (CR) became minimal residual disease (MRD) negative, Carlo-Stella continues. These data support the efficacy of RG6234 and indicate the potential for achieving long-term, durable responses with this agent.

Carmelo Carlo-Stella, MD, PhD, discusses updated results from a phase 1 dose-escalation study of subcutaneous and intravenous RG6234 in relapsed/refractory multiple myeloma.

Carmelo Carlo-Stella, MD, PhD

Articles

Dr Carlo-Stella on the FDA Approval of Glofitamab in Relapsed/Refractory DLBCL

Dr. Carlo-Stella on the Investigation of RG6234 in R/R Multiple Myeloma

Dr Carlo-Stella on Updated Results on RG6234 Activity in R/R Multiple Myeloma