ASCO Annual Meeting

ASCO Annual Meeting

Issue: July 25, 2018
June 03, 2018
3 min read

Once-weekly carfilzomib effective for relapsed, refractory myeloma

Issue: July 25, 2018
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CHICAGO — A higher once-weekly dose of carfilzomib significantly extended PFS compared with lower twice-weekly dosing among patients with relapsed and refractory multiple myeloma, according to an interim analysis of the randomized phase 3 A.R.R.O.W. study presented at ASCO Annual Meeting.

The results — published simultaneously in The Lancet Oncology — showed patients assigned the once-weekly dose of carfilzomib (Kyprolis, Amgen) also appeared more likely to achieve response.

Twice-weekly carfilzomib — a selective proteasome inhibitor — administered at 27 mg/m2 is approved for treatment of relapsed or refractory multiple myeloma.

The phase 1/phase 2 CHAMPION-1 trial assessed once-weekly carfilzomib dosing and established a maximum tolerated dose of 70 mg/m2 when administered with dexamethasone.

In the open-label A.R.R.O.W. study, Maria-Victoria Mateos, MD, PhD, director of the myeloma unit and coordinator of the clinical trials unit at University Hospital of Salamanca in Spain, and colleagues assessed PFS among patients with relapsed and refractory myeloma who received once-weekly or twice-weekly carfilzomib.

Researchers recruited 578 patients aged 18 years or older, all of whom underwent two or three prior treatments, including a proteasome inhibitor and immunomodulatory agent.

Eligible patients were refractory to their most recent therapy — including bortezomib (Velcade, Takeda) or ixazomib (Ninlaro, Takeda) — with measurable disease, and they had ECOG performance status of 0 or 1.

Investigators randomly assigned patients 1:1 to once-weekly or twice-weekly carfilzomib with dexamethasone in 28-day cycles.

Those assigned the once-weekly regimen received carfilzomib administered via 30-minute infusions on days 1, 8 and 15 of all cycles (20 mg/m2 on day 1 of cycle 1, followed by 70 mg/m2 thereafter). Those assigned the twice-weekly regimen received carfilzomib via 10-minute IV infusions on days 1, 2, 8, 9, 15 and 16 of all cycles (20 mg/m2 on days 1 and 2 during the first cycle, followed by 27 mg/m2 thereafter).

All patients received dexamethasone (40 mg on days 1, 8 and 15 of all cycles, and day 22 of cycles 1 through 9 only).

Treatment continued until unacceptable toxicity or disease progression.

PFS between groups in the intent-to-treat population served as the primary endpoint.

Mateos and colleagues stratified patients by age, International Staging System stage at study entry or baseline, and whether they were refractory to bortezomib treatment.

Investigators also performed safety analyses among all randomly assigned patients who received at least one treatment dose.

The efficacy analysis included 478 patients (once-weekly, n = 240; twice weekly, n = 238).


Patients assigned once-weekly carfilzomib achieved significantly longer median PFS (11.2 months vs. 7.6 months; HR = 0.69; 95% CI, 0.54-0.83). Researchers also reported a higher overall response rate (62.9% vs. 40.8%; P < .0001) and rate of complete response or better (7.1% vs. 1.7%) in the once-weekly group.

More patients assigned once-weekly dosing experienced grade 3 or worse adverse events (68% vs. 62%). The most common adverse events were anemia (18% in each dosing group), pneumonia (10% for once-weekly dosing vs. 7% for twice-weekly dosing) and thrombocytopenia (7% vs. 7%). Fewer patients in the once-weekly group experienced grade 3 or worse cardiac failure (3% vs. 4%).

At data cutoff, 126 patients had died (once-weekly group, n = 58; twice-weekly group, n = 68).

Five (2%) patients assigned once-weekly carfilzomib died due to treatment-related causes. These included one case each of sepsis, tumor lysis syndrome, acute respiratory distress syndrome and acute lung injury. Two patients (1%) assigned twice-weekly carfilzomib died due to treatment-related causes; these included one case each of congestive heart failure and plasma cell myeloma).

“Once-weekly carfilzomib appears safe and more effective with a convenient dosing regimen versus the twice-weekly schedule for the treatment of patients with relapsed and refractory multiple myeloma,” Mateos and colleagues concluded. – by Mark Leiser


For more information:

Mateos V-M, et al. Abstract 8000. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.

Moreau P, et al. Lancet Oncol. 2018;doi:10.1016/S1470-2045(18)30354-1.


Disclosures: Amgen funded this study. Mateos reports honoraria from and consultant/advisory roles with Amgen, Celgene, Janssen-Cilag and Takeda. Please see the abstract for all other authors’ relevant financial disclosures.