Cevostamab Elicits Responses in Younger and Older Patients with Relapsed/Refractory Myeloma

Amrita Y. Krishnan, MD

Cevostamab (RG 6160) generated responses and was well tolerated in younger and older patients with relapsed/refractory multiple myeloma, according to data from the phase 1 GO39775 trial (NCT03275103) presented at the 19th International Myeloma Society Annual Meeting.

Findings showed that patients under the age of 65 who were treated with cevostamab (n = 31) achieved an overall response rate (ORR) of 58.1% (95% CI, 39.1%-77.1%), including a stringent complete response (sCR) rate of 6.5%, a complete response (CR) rate of 3.2%, and a very good partial response (VGPR) rate of 25.8%. Overall, 35.5% of patients experienced a VGPR or better.

Among patients 65 years or older (n = 29), cevostamab generated an ORR of 55.2% (95% CI, 35.4%-75.0%) with sCR and VGPR rates of 6.9% and 20.7%, respectively. Overall, 27.6% of patients had a VGPR or better.

“In terms of efficacy, the drug was highly active in both older and younger patients. The responses appeared durable,” Amrita Y. Krishnan, MD, a hematologist at the City of Hope Comprehensive Cancer Center, said in a poster presentation of the data.

Approximately 64% of patients diagnosed with multiple myeloma in the United States are 65 years or older. Advancing age can often lead to a decline in patients’ immune function and increase their chances for comorbidities, leaving them more vulnerable to treatment-related adverse effects (AEs).

The GO39775 trial investigated cevostamab, a bispecific antibody that utilizes dual binding to effectively induce T-cell activation and potent T-cell–directed killing of cancerous cells.

GO39775 enrolled patients with advanced relapsed or refractory multiple myeloma, who had no established therapy that was available, appropriate, or tolerable. Patients were required to have an ECOG score of 0 or 1, and prior treatment with CAR T-cell therapy, antibody-drug conjugates, and bispecific antibodies was allowed.

In the single step-up, dose-escalation portion of the trial, patients received step-up dosing of cevostamab before reaching targeted doses of 132 mg, 160 mg, and 198 mg. On day 1 of cycle 1, patients received 3.6 mg of cevostamab. On day 8 of cycle 1, patients received a target dose of 132 mg (n = 7), 160 mg (n = 8), or 198 mg (n = 9). Patients continued with their target dose of day 1 of cycles 2 to 17, receiving treatment every 3 weeks. Notably, lower target doses of cevostamab were also explored in this portion of the trial, but only data from patients treated with target doses of 132 mg to 198 mg were presented.

In the double step-up escalation- and expansion-portion of the trial, patients (n = 36) received 0.3 mg of cevostamab on day 1 of cycle 1, 3.6 mg of cevostamab on day 8 of cycle 1, and 160 mg of cevostamab on day 15 of cycle 1. In cycles 2 to 17, 160 mg of cevostamab was administered on day 1, with treatment occurring every 3 weeks.

The median age of younger patients was 57 years (range, 45-64), and the median age of older patients was 70 years (range, 65-82). Among all patients, the median number of prior lines of therapy was 6 (range, 2-12). Almost all patients in both groups were triple-class refractory, and many were penta-drug refractory. More than half of patients in both groups had high-risk cytogenetics, and approximately 20% of patients in both groups had documented extramedullary disease.

“The baseline patient characteristics and disease characteristics were generally well balanced in both the younger and older patient groups,” Krishnan noted.

When evaluating baseline biomarker characteristics from bone marrow samples, FcRH5 expression and CD8 T-cell subsets were similar between the younger and older groups. Notably, older patients appeared to have lower T-cell levels than younger patients.

Regarding safety, cytokine release syndrome (CRS) was the most common any-grade AE in both age groups, occurring in 83.9% and 82.8% of patients in the younger and older cohorts, respectively. However, the only grade 3 CRS event was reported in 1 patient younger group. Any-grade immune effector cell-associated neurotoxicity syndrome (ICANS) associated with CRS was reported in 1 patient in the younger group and 3 patients in the older group. One grade 3 ICANS event occurred in a patient in the older group.

Additionally, any-grade infections occurred in 61.3% of patients younger than 65 years and in 41.4% of patients at least 65 years old. Rates of grade 3 infections were 19.4% and 20.7%, respectively, and rates of grade 4 infections were 9.7% and 0, respectively. One patient in the older group had grade 5 hemophagocytic lymphohistiocytosis.

Three patients experienced AEs that led to discontinuation of cevostamab in the 65 years and older age group due to CRS, rash, and confused state, respectively. 1 more patient in the older group and 4 in the younger group had AEs that led to treatment discontinuation, though they were not related to cevostamab.

“Cevostamab was efficacious and well tolerated in heavily pretreated patients with myeloma, including those less than 65 [years old] and those over age 65,” Krishnan concluded

Reference

Krishnan A, Cohen A, Trudel S, et al. P-012 Cevostamab is efficacious and well tolerated in patients aged < 65 and ≥65 years with relapsed/refractory multiple myeloma (RRMM). Presented at: 19th International Myeloma Society Annual Meeting; August 25-27, 2022; Los Angeles, California. Abstract P-012.