Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2017

Rates of peripheral neuropathy (PN) in patients with relapsed and refractory multiple myeloma (RRMM) treated with carfilzomib vs comparators in pivotal Phase 3 trials (#192)

Ruben Niesvizky 1 , Vania Hungria 2 , P. Joy Ho 3 , Darrell J White 4 , Lifen Zhou 5 , Karim S Iskander 5 , Laura Rosiñol 6 , Kristy Shipman 7
  1. 1Center for Myeloma, New York Presbyterian Hospital-Weill Cornell Medical Center, New York, NY, USA
  2. Santa Casa de São Paulo Medical School, , São Paulo, Brazil
  3. Institute of Haematology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
  4. Dalhousie University and QEII Health Sciences Centre, Halifax, Nova Scotia, Canada
  5. Amgen Inc, Thousand Oaks, CA, USA
  6. Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clinic, Barcelona, Spain
  7. Amgen Australia, North Ryde, NSW, Australia


PN is a dose-limiting toxicity for some anti-MM agents, including the proteasome inhibitor (PI) bortezomib (V). Carfilzomib (K), a PI associated with low PN, was evaluated in 2 recent phase 3 studies in RRMM patients.


This analysis evaluated PN rates in ASPIRE (K [27 mg/m2]-lenalidomide [R]-dexamethasone[d] [KRd] vs Rd in relapsed MM) and ENDEAVOR (Kd [K 56 mg/m2] vs Vd in RRMM). We evaluated grade ≥2 PN during treatment, patient-reported outcomes (LS mean difference QLQ-C30 pain, FACT/GOG-neurotoxicity subscales), and progression-free survival (PFS) in patients with baseline history of PN.


In ASPIRE, grade ≥2 PN rate was low (8.9% [KRd] vs 8.0% [Rd]; OR [95% CI]: 1.132 [0.683, 1.876]; p=0.685). Pain subscale scores were similar between arms (ITT [95% CI]: -1.02 [-3.77, 1.73]; p=0.47). Median PFS was similar for K patients with BL grade ≥2 PN vs any baseline PN (24.2 vs 23.2 months). In ENDEAVOR, grade ≥2 PN rate during the study was significantly lower with Kd vs Vd (6.0% vs 32.0%; OR (95% CI) 0.137 (0.089, 0.210); p<0.0001). Patients had significantly lower pain (ITT [95% CI] -2.35 [-4.30, -0.39]; p=0.0186) and neurotoxicity subscale (Safety, [95% CI] 0.84 [0.40, 1.28]; p=0.0002) scores with Kd vs Vd. Median PFS (months) with Kd vs Vd in patients with BL history of grade ≥2 PN was 18.6 vs 5.6; HR [95% CI] 0.42 [0.266, 0.677], and 18.7 vs 9.4; HR [95% CI] 0.54 [0.410, 0.715] in patients with any baseline PN.


In ENDEAVOR, Kd resulted in less PN vs Vd; in ASPIRE, PN rate was similar for KRd vs Rd. Median PFS was longer with KRd and Kd vs Rd and Vd, respectively, in patients with BL grade ≥2 PN. Improved pain and neurotoxicity outcomes with K may be attributed to better disease control and/or lower PN rates.