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2017 ASCO Annual Meeting!

Session: Hematologic Malignancies—Plasma Cell Dyscrasia

Type: Oral Abstract Session

Time: Sunday June 4, 9:45 AM to 12:45 PM

Location: E354b

Impact of denosumab (DMB) compared with zoledronic acid (ZA) on renal function in the treatment of myeloma bone disease.

Multiple Myeloma

Hematologic Malignancies—Plasma Cell Dyscrasia

2017 ASCO Annual Meeting

Abstract No:

J Clin Oncol 35, 2017 (suppl; abstr 8005)

Author(s): Noopur S. Raje, G. David Roodman, Wolfgang Willenbacher, Kazuyuki Shimizu, Ramon Garcia-Sanz, Brian G. Durie, Li Zhu, Paul C. Cheng, Sumita Bhatta, Evangelos Terpos; Massachusetts General Hospital Cancer Center, Boston, MA; Indiana University, Indianapolis, IN; Medical University of Innsbruck, Innsbruck, Austria; National Hospital Organization Higashi Nagoya National Hospital, Nagoya, Japan; Hospital Universitario de Salamanca, Salamanca, Spain; Cedars-Sinai Comprehensive Cancer Center, Los Angeles, CA; Amgen Inc., Thousand Oaks, CA; National and Kapodistrian University of Athens, Athens, Greece

Abstract Disclosures


Background: Osteolytic bone disease and renal dysfunction are complications of multiple myeloma. ZA, used for the prevention and treatment of bone complications, can be nephrotoxic. DMB inhibits RANKL and thereby osteoclast function, and is not renally cleared. This international, phase III, randomized, double blind study evaluates the efficacy and safety of DMB compared with ZA in newly diagnosed myeloma patients (pts). Methods: Eligible pts were randomized 1:1 to DMB 120mg SC Q4W or ZA 4mg (renally adjusted) IV Q4W along with anti-myeloma therapy. Pts with baseline CrCl<30mL/min were excluded due to ZA dosing restrictions. The primary endpoint was non-inferiority of DMB to ZA with respect to time to first on-study SRE. Overall survival (OS) was a secondary endpoint; progression-free survival (PFS) was an exploratory endpoint. Renal toxicity and safety were assessed. Results: 1718 pts were randomized, 859 to each arm. Baseline renal insufficiency (CrCl ≤ 60mL/min) was reported in 26.7% of pts. DMB was non-inferior to ZA (P = 0.01) in delaying time to first on-study SRE. Fewer AEs potentially related to renal toxicity were reported with DMB compared to ZA overall (10.0% vs 17.1%, P< 0.001) in those with baseline CrCl > 60mL/min (8.8% vs 14.2%) and particularly in those with baseline CrCl ≤ 60mL/min (12.9% vs 26.4%). 12.5% of pts on DMB experienced an increase in creatinine, compared to 20.8% of those on ZA. Median cumulative exposure (Q1, Q3) to DMB was 15.75 months (8.18, 25.79) compared to 14.78 months (7.46, 24.87) for ZA. PFS yielded a HR (95%CI) of 0.82 (0.68, 0.99); descriptive P = 0.036. OS HR (95%CI) between DMB and ZA was 0.9 ([0.70, 1.16]; P = 0.41), with fewer deaths in DMB (121 [14.1%]) than in ZA (129 [15.0%]). Conclusions: DMB achieved the primary endpoint of non-inferiority to ZA in delaying time to first on study SRE in pts with newly diagnosed MM. Pts on DMB had a significantly lower rate of renal AEs compared to ZA; more importantly this rate was 2-fold lower in pts with renal insufficiency (CrCl≤60mL/min). The bone specific benefits in combination with the renal function results and possible prolongation of PFS with DMB therapy is promising. Clinical trial information: NCT01345019

Other Abstracts in this Sub-Category:


1. Daratumumab (DARA) in combination with carfilzomib, lenalidomide, and dexamethasone (KRd) in patients (pts) with newly diagnosed multiple myeloma (MMY1001): An open-label, phase 1b study.

Meeting: 2017 ASCO Annual Meeting Abstract No: 8000 First Author: Andrzej J. Jakubowiak
Category: Hematologic Malignancies—Plasma Cell Dyscrasia - Multiple Myeloma


2. Lenalidomide, doxorubicin hydrochloride and dexamethasone versus bortezomib, lenalidomide, and dexamethasone prior to scheduled stem cell transplant in newly diagnosed myeloma.

Meeting: 2017 ASCO Annual Meeting Abstract No: 8001 First Author: Stefan Knop
Category: Hematologic Malignancies—Plasma Cell Dyscrasia - Multiple Myeloma


3. An open-label, single arm, phase IIa study of bortezomib, lenalidomide, dexamethasone, and elotuzumab in newly diagnosed multiple myeloma.

Meeting: 2017 ASCO Annual Meeting Abstract No: 8002 First Author: Jacob Laubach
Category: Hematologic Malignancies—Plasma Cell Dyscrasia - Multiple Myeloma