Once-weekly versus twice-weekly carfilzomib in patients with newly diagnosed multiple myeloma: a pooled analysis of two phase I/II studies

Abstract

Twice-weekly carfilzomib is approved at 27 and 56 mg/m2 to treat relapsed multiple myeloma patients. In the phase III study ARROW, once-weekly 70 mg/m 2 carfilzomib prolonged the median progression-free survival of relapsed multiple myeloma patients in comparison with twice-weekly 27 mg/m2 carfilzomib, without adding significant toxicity. Data were pooled from two phase I/II studies of newly diagnosed multiple myeloma patients who received nine induction cycles of carfilzomib (either 70 mg/m2 once-weekly or 36 mg/m2 twice-weekly), cyclophosphamide and dexamethasone, followed by carfilzomib maintenance. Overall, 121 transplant-ineligible patients with newly diagnosed multiple myeloma were analyzed (once-weekly, n=63; twice-weekly, n=58). We found no significant difference in median progression-free survival [35.7 months (95%CI: 23.7-not reached, NR) vs 35.5 months (95%CI: 24.3-NR); HR: 1.39; P=0.26] and 3-year overall survival [70% [95%CI: 59%-84%) vs 72% (95%CI: 60%-85%); HR: 1.27; P=0.5] between once-weekly and twice-weekly carfilzomib. From the start of maintenance, 3-year progression-free survival [47% (95%CI: 33%-68%) vs 51% (95%CI: 38%-70%); HR: 1.04; P=0.92] and overall survival [72% (95%CI: 58%-89%) vs 73% (95%CI: 59%-90%); HR: 0.82; P=0.71] were similar in the once- versus twice-weekly carfilzomib. The rate of grade 3-5 hematologic (24% vs 30%; P=0.82) and non-hematologic (38% vs 41%; P=0.83) adverse events was similar in the two groups. Once-weekly 70 mg/m2 carfilzomib as induction and maintenance therapy for newly diagnosed multiple myeloma patients was as safe and effective as twice-weekly 36 mg/m2 carfilzomib and provided a more convenient schedule. The trials are registered at clinicaltrials.gov identifiers: 01857115 (IST-CAR-561) and 01346787 (IST-CAR-506).

Trial registration: ClinicalTrials.gov NCT01346787.

Copyright© 2019 Ferrata Storti Foundation.

Figures

Figure 1.

Analysis profile. N: number; AE: adverse events; PD: progressive disease; SPM: second primary malignancy.

Figure 2.

Once-weekly versus twice-weekly carfilzomib in patients with newly diagnosed multiple myeloma. (A) Intention-to-treat progression-free survival (ITT PFS). (B) Intention-to-treat progression-free survival 2 (ITT PFS-2). (C) Intention-to-treat overall survival (ITT OS). (Note that PFS-2 was calculated from the date of enrollment to the date of second relapse/progression or death or the date the patient was last known to be in remission.)

Figure 3.

Analysis from start of maintenance therapy. (A) Progression-free survival from start of maintenance therapy (PFS_m). (B) Progression-free survival 2 from start of maintenance therapy (PFS-2_m). (C) Overall survival from start of maintenance therapy (OS_m). (Note that PFS-2 was calculated from the date of enrollment to the date of second relapse/progression or death or the date the patient was last known to be in remission.)