Carfilzomib plus Filanesib versus Carfilzomib in Patients with Advanced Multiple Myeloma

Conference Correspondent  - Conference Correspondent, ASH

Filanesib (ARRY-520) is a first-in-class kinesin spindle protein (KSP) inhibitor that is being evaluated in combination with the proteasome inhibitor carfilzomib versus carfilzomib alone in an ongoing, randomized, open-label phase 2 study in patients with relapsed and/or refractory multiple myeloma (RRMM); Zonder and colleagues presented preliminary results of this trial.1 A total of 77 patients who were carfilzomib-naïve, had received at least 2 prior regimens, including bortezomib and an immunomodulatory drug (IMiD), and were refractory to the last regimen were enrolled in the trial. Patients were randomized 2:1 to receive either carfilzomib (20/27 mg/m2 intravenously [IV]) plus filasenib (1.25 mg/m2 IV) (arm A; n = 52) or carfilzomib alone (arm B; n = 25); of these, 50 patients were evaluable for this analysis. Of the patients in arm A, 47% had high-risk cytogenetics compared with 44% in arm B. In addition, 60% of the patients in both arms were dual-refractory to an IMiD and bortezomib.

In this heavily pretreated patient population (median prior regimens 4-5 for the 2 arms), carfilzomib/filanesib treatment resulted in an increased median progression-free survival (PFS) of 8.5 months versus 3.7 months for carfilzomib alone. The overall response rate (ORR) was 28%, including 3 very good partial responses and 9 partial responses, compared with an ORR of 12% with carfilzomib alone. Notably, the patient subset with double-refractory disease to IMiDs and bortezomib achieved an ORR of 33% with both carfilzomib/filanesib and carfilzomib alone. Low levels of alpha-1-acid glycoprotein (AAG) was associated with higher ORR and PFS rates in both arms.

Grade 3/4 hematologic laboratory abnormalities were higher with carfilzomib/filanesib therapy and included neutropenia (26% vs 12%) and thrombocytopenia (31% vs 12%). Dyspnea and fatigue were the only grade 3/4 nonhematologic adverse events reported (5% vs 8% and 7% vs 4%, respectively). Based on these preliminary study results, the authors concluded that carfilzomib plus filanesib was a promising steroid-sparing treatment option for patients with RRMM, including those with double-refractory disease. In addition, patients with high AAG levels may be less likely to respond to either filanesib or carfilzomib.

  1. Zonder JA, et al. ASH 2015. Abstract 728.
Related Items
No Link between Long-Term Eltrombopag Treatment and Incidence of Cataracts in Adult Patients with Chronic ITP During EXTEND
Conference Correspondent  published on December 27, 2017 in ASH
Eltrombopag Treatment Improved Platelet Counts in Patients with Persistent or Chronic ITP
Conference Correspondent  published on December 27, 2017 in ASH
Fostamatinib-Treated Patients with Persistent/Chronic ITP Maintained Long-Term Responses
Conference Correspondent  published on December 27, 2017 in ASH
Avatrombopag Superior to Placebo for the Treatment of Chronic ITP
Conference Correspondent  published on December 27, 2017 in ASH
Subcutaneous Romiplostim Increased Platelet Response in Children with ITP
Conference Correspondent  published on December 27, 2017 in ASH
Centers for Disease Control and Prevention Guidelines on Opioid Use for Cancer Pain
Chase Doyle
TOP - August 2017, Vol 10, No 3 published on August 1, 2017 in Conference Correspondent, HOPA
Maintenance Chemotherapy After Hematopoietic Stem-Cell Transplantation
Chase Doyle
TOP - August 2017, Vol 10, No 3 published on August 1, 2017 in Conference Correspondent, HOPA
Graft-versus-Host Disease: Breakthroughs on the Horizon
Chase Doyle
TOP - August 2017, Vol 10, No 3 published on August 1, 2017 in Conference Correspondent, HOPA
Basket Clinical Trials: A New Era in Cancer Treatment
Chase Doyle
TOP - August 2017, Vol 10, No 3 published on August 1, 2017 in Conference Correspondent, HOPA
Burnout Rates High for Pharmacists in Hematopoietic Stem-Cell Transplantation
Chase Doyle
TOP - August 2017, Vol 10, No 3 published on August 1, 2017 in Conference Correspondent, HOPA
Last modified: April 27, 2020