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Expert Point of View: Craig Hofmeister, MD, MPH


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“The IKEMA trial is based on the interest of adding a CD38 naked antibody to a carfilzomib-plus-dexamethasone skeleton, a protocol nearly identical to the recently presented CANDOR trial,” said Craig Hofmeister MD, MPH, Associate Professor of Hematology and Oncology at the Winship Cancer Institute of Emory University, Atlanta, in an interview with The ASCO Post.

The phase III CANDOR trial found a 37% reduction in the risk of disease progression (P = .0014) with daratumumab plus carfilzomib and dexamethasone (Kd) over Kd alone, according to the late-breaking presentation at the 2019 American Society of Hematology (ASH) Annual Meeting by Usmani et al.1

Comparing Results From IKEMA and CANDOR

The IKEMA and CANDOR trials are similar in that they included an anti-CD38 antibody paired with Kd. Dr. Hofmeister looked deeper at these study findings for some important takeaways, focusing on the rates of grade 3 or 4 infections, key patient characteristics, response rates, and dosing.

Grade 3 or 4 infections were reported in 22.1% of patients receiving isatuximab plus Kd compared with 14.7% of those given Kd alone, which was similar to those reported in CANDOR (28.9% vs 15.7%, respectively). “Clearly, these regimens are immunosuppressive and should prompt us to carefully consider infection prophylaxis at the outset,” he noted.

Regarding differences in their patient populations, he noted that CANDOR allowed prior carfilzomib, whereas IKEMA did not, although patients were required to be sensitive to carfilzomib at the time of enrollment. In addition, CANDOR may have allowed patients with more renal insufficiency, at 15 to 50 mL/min in 13.9% of patients treated, whereas IKEMA reported 20.2% of patients had a creatinine clearance up to 60 mL/min/1.73 m2 by MDRD [Modification of Diet in Renal Disease Study equation], “without further details,” commented Dr. Hofmeister.

By response rates, he observed the complete response proportion was 39.7% in IKEMA and 28.5% in CANDOR, “but the bump from using the CD38 antibody was 18% in CANDOR and just 12% in IKEMA…. The addition of the CD38 antibody led to an approximate 15% improvement in the proportion with minimal residual disease, similar to CANDOR,” Dr. Hofmeister noted.

“Overall, the regimens reported in CANDOR and IKEMA were effective in the majority of patients,” Dr. Hofmeister concluded, suggesting “perhaps only the number of doses distinguishes the two cocktails.”

Median exposure to the CD38 antibody totaled 80 weeks (162 doses) in IKEMA for isatuximab and 78 weeks (88 doses) in CANDOR for daratumumab. 

DISCLOSURE: Dr. Hofmeister has served as a consultant or advisor to Celgene, Imbrium, Janssen Oncology, Karyopharm, Nektar, Oncopeptides, and Sanofi Pasteur and has received research funding from Bristol-Myers Squibb, Celgene, and Cellularity.

REFERENCE

1. Usmani SZ, Quach H, Mateos MV, et al: Carfilzomib, dexamethasone, and daratumumab vs carfilzomib and dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma: Primary analysis results from the randomized, open-label, phase III study CANDOR (NCT03158688). 2019 ASH Annual Meeting & Exposition. Abstract LBA-6. Presented November 21, 2019.


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