LBA28 - Carfilzomib (K) vs low-dose corticosteroids and optional cyclophosphamide (Cy) in patients (pts) with relapsed and refractory multiple myeloma (RRM...

Date 29 September 2014
Event ESMO 2014
Session Haematological malignancies
Topics Anticancer agents
Plasma Cell Dyscrasias
Therapy
Biological therapy
Presenter Heinz Ludwig
Citation Annals of Oncology (2014) 25 (5): 1-41. 10.1093/annonc/mdu438
Authors H. Ludwig1, T. Masszi2, M.T. Petrucci3, A. Palumbo4, L. Rosiñol5, A. Nagler6, K.L. Yong7, J. Minarik8, M. Dimopoulos9, V. Maisnar10, D. Rossi11, H. Kasparu12, D. Ben-Yehuda13, I. Hardan14, M. Jenner15, K. Rajangam16, J.F. San Miguel17, R. Hájek18
  • 11st Department Of Medicine, Wilhelminen Cancer Research Institute, Wilhelminenspital, 1160 - Vienna/AT
  • 2Department Of Hematology & Stem Cell Transplant, St. István and St. László Hospital of Budapest, Budapest/HU
  • 3Hematology Service, Department Of Cellular Biotechnology And Hematology, Sapienza University of Rome, Rome/IT
  • 4Department Of Hematology, University of Torino, Torino/IT
  • 5Amyloidosis And Myeloma Unit, Hospital Clínic de Barcelona, Barcelona/ES
  • 6Hematology Division And Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel-Hashomer/IL
  • 7Department, University College London Cancer Institute, London/GB
  • 8Department Of Internal Medicine Iii, University Hospital Olomouc, Olomouc/CZ
  • 9Department Of Clinical Therapeutics, Alexandra Hospital, Athens/GR
  • 10Department Of Clinical Hematology, Charles University Teaching Hospital, Hradec Králové/CZ
  • 11Department Of Translational, Amedeo Avogadro University of Eastern Piedmont, Novara/IT
  • 12Department Of Internal Medicine, Hospital Elisabethinen Linz, Linz/AT
  • 13Department Of Hematology, Hadassah Medical Center, Jerusalem/IL
  • 14Department Of Hematology, Meir Medical Center, Kfar-Saba/IL
  • 15Department, Southampton General Hospital, Southampton/GB
  • 16Department, Onyx Pharmaceuticals Inc, an Amgen subsidiary, South San Francisco/US
  • 17Department Of Hematology, Clinica Universidad de Navarra, Navarra/ES
  • 18Department, University Hospital Ostrava and Faculty of Medicine Ostrava, Brno/CZ

Abstract

Aim

To compare K with low-dose corticosteroids and optional Cy in RRMM (NCT01302392).

Methods

Pts were randomized 1:1 to receive K or an active control of low-dose corticosteroids and optional Cy. Pts received K (10-min IV infusion) on Day (D) 1, 2, 8, 9, 15, 16 of a 28-D cycle (20 mg/m2 on D 1 and 2 of Cycle 1; 27 mg/m2 thereafter) or 84 mg of dexamethasone (or equivalent corticosteroid) with optional Cy (maximum 1400 mg) per 28-D cycle. The primary endpoint was overall survival (OS) with 80% power to detect a hazard ratio (HR) of 0.7 (median OS assumptions: K, 8.6 months [mo]; control: 6 mo). Secondary endpoints included progression-free survival (PFS), overall response rate (ORR) and safety.

Results

Data are presented for the K group followed by the control group. Between Sept 2010 and Oct 2012, 315 pts (278 from Europe) were randomized (K: 157 pts; control: 158 pts). Baseline characteristics were balanced between the groups. Median age was 65.0 yrs (range: 32–85). Pts received 5 (median) prior regimens in each group; median time since diagnosis was 6.0 yrs and 5.4 yrs. Median treatment duration was 16.3 weeks and 10.7 weeks; 92% of pts in the control group received Cy. Median relative dose intensity (actual dose/planned dose) was 99.9% in each group. The study did not meet the primary endpoint for OS (HR = 0.975; 95% confidence interval [CI]: 0.760–1.249; P = 0.4172). Median OS was 10.2 mo (95% CI: 8.4–14.4) and 10.0 mo (95% CI: 7.7–12.0). Median (range) follow-up for OS was 27.8 mo (0.1–42.5) and 29.8 mo (0.0–44.8). Median PFS was 3.7 mo (95% CI: 2.8–4.2) and 3.3 mo (95% CI: 2.2–5.2). The ORR was 19.1% (95% CI: 13.3–26.1) and 11.4% (95% CI: 6.9–17.4). Treatment discontinuation due to an adverse event (AE) occurred in 14.6% and 20.3% of pts; 10.2% and 12.4% of pts died on study due to an AE. Grade ≥3 treatment-emergent AEs (≥5%) included anemia (25.5% vs 30.7%), thrombocytopenia (24.2% vs 22.2%), neutropenia (7.6% vs 12.4%), acute renal failure (7.6% vs 3.3%), pneumonia (6.4% vs 12.4%), and renal failure (5.1% vs 1.3%).

Conclusions

Median OS for single-agent K (10.2 mo) was similar to the active control arm (10 mo) in these heavily pretreated pts with RRMM.

Disclosure

H. Ludwig: Research funding: Celgene, Janssen-Cilag, Mundipharma; Advisory Board: Celgene, Bristol-Meyers, Janssen-Cilag, Onyx; M.T. Petrucci: Consultancy and honoraria for Janssen-Cilag, Celgene, and Bristol-Myers Squibb; A. Palumbo: Consultancy -Amgen, Bristol-Myers Squibb, Celgene, Janssen, Millenium, Onyx;Honoraria -Amgen, Bristol-Myers Squibb, Celgene, Janssen, Millenium, Onyx; L. Rosiñol: honoraria from Janssen and Celgene; A. Nagler: Research funding from Onyx; M.A. Dimopoulos: Honoraria from Onyx V. Maisnar: Consultancy - Celgene; Honoraria directly received from an entity - Celgene, Janssen, Amgen;Membership on an entity's board of directors, speakers bureau,or its advisory committees - Celgene K. Rajangam: employee of Onyx; J.F. San Miguel: He has participated in several compensated advisory boards for Millennium, Onyx, Celgene, Novartis, Janssen; R. Hájek: consultancy–Celgene,Merck; Honoraria - Celgene, Janssen, Merck. All other authors have declared no conflicts of interest.