Daratumumab, bortezomib, melphalan, and prednisone versus bortezomib, melphalan, and prednisone alone in transplant-ineligible Asian patients with newly diagnosed multiple myeloma: final analysis of the phase 3 OCTANS Study

Abstract

The superiority and tolerability of daratumumab plus bortezomib/melphalan/prednisone (D-VMP) versus bortezomib/melphalan/prednisone (VMP) in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM) was previously described in the global phase 3 ALCYONE study. The primary analysis of the phase 3 OCTANS study further demonstrated the superiority and tolerability of D-VMP (n = 144) versus VMP (n = 71) in transplant-ineligible Asian patients with NDMM. The current analysis describes the final efficacy and safety outcomes for D-VMP versus VMP in OCTANS, with a follow-up of > 3 years. D-VMP demonstrated a benefit versus VMP with regard to the rate of very good partial response or better (80.1% vs. 47.3%), median progression-free survival (38.7 vs. 19.2 months), median time to next treatment (46.8 vs. 20.6 months), rate of complete response or better (46.6% vs. 18.9%), median duration of response (41.3 vs. 18.5 months), achievement of minimal residual disease (MRD) negativity (40.4% vs. 10.8%), and sustained MRD negativity for ≥ 12 months (24.7% vs. 1.4%) and ≥ 18 months (15.1% vs. 1.4%). Median progression-free survival was longer among patients who achieved MRD negativity and sustained MRD negativity. The progression-free survival benefit observed with D-VMP was preserved across most clinically relevant subgroups, including patients with high-risk cytogenetics. No new safety concerns were identified with extended follow-up. This final analysis of OCTANS continues to demonstrate a clinical benefit for D-VMP versus VMP in transplant-ineligible Asian patients with NDMM, consistent with the global ALCYONE study, and supports the use of daratumumab combinations in this population. Trial registration: ClinicalTrials.gov Identifier NCT03217812 submitted July 13, 2017.

Keywords: Daratumumab; Minimal residual disease; Multiple myeloma; Response; Safety; Survival.

Fig. 1

Patient disposition D-VMP, daratumumab plus bortezomib/melphalan/prednisone; VMP, bortezomib/melphalan/prednisone ^*Reason captured was “patient refused further study treatment”

Fig. 2

Depth of response with D-VMP and VMP in the ITT population shown as (a) best confirmed response and (b) MRD negativity (10^–5). D-VMP, daratumumab plus bortezomib/melphalan/prednisone; VMP, bortezomib/melphalan/prednisone; ITT, intent-to-treat; MRD, minimal residual disease; sCR, stringent complete response; CR, complete response; VGPR, very good partial response; PR, partial response; ORR, overall response rate

Fig. 3

PFS in the ITT population PFS, progression-free survival; ITT, intent-to-treat; D-VMP, daratumumab plus bortezomib/melphalan/prednisone; VMP, bortezomib/melphalan/prednisone; HR, hazard ratio; CI, confidence interval

Fig. 4

Cytogenetic subgroup analysis of PFS in the ITT population PFS, progression-free survival; ITT, intent-to-treat; D-VMP, daratumumab plus bortezomib/melphalan/prednisone; VMP, bortezomib/melphalan/prednisone; HR, hazard ratio; CI, confidence interval; ISS, International Staging System; NE, not estimable; HRCA, high-risk cytogenetic abnormality. *Renal insufficiency defined as baseline creatinine clearance ≤ 60 mL/min. ^†Standard cytogenetic risk defined as none of the following HRCAs: t(4;14), t(14;16), and del(17p). ^‡High cytogenetic risk defined as ≥ 1 of the following HRCAs: t(4;14), t(14;16), and/or del(17p). ^§Revised standard cytogenetic risk defined as none of the following HRCAs: t(4;14), t(14;16), del(17p), t(14;20), gain(1q21), and amp(1q21). ^¶Revised high cytogenetic risk defined as ≥ 1 of the following HRCAs: t(4;14), t(14;16), del(17p), t(14;20), gain(1q21), and/or amp(1q21). ^#Gain(1q21) defined as 3 copies of chromosome 1q21, with or without other HRCAs. ^ǁAmp(1q21) defined as ≥ 4 copies of chromosome 1q21, with or without other HRCAs. ^**Gain(1q21) or amp(1q21) defined as ≥ 3 copies of chromosome 1q21, with or without other HRCAs. ^††1 HRCA defined as only 1 of the following HRCAs: t(4;14), t(14;16), del(17p), t(14;20), gain(1q21), or amp(1q21). ^‡‡≥2 HRCAs defined as ≥ 2 of the following HRCAs: t(4;14), t(14;16), del(17p), t(14;20), gain(1q21), and/or amp(1q21). ^§§Isolated gain(1q21) defined as 3 copies of chromosome 1q21 without any other HRCAs. ^¶¶Isolated amp(1q21) defined as ≥ 4 copies of chromosome 1q21 without any other HRCAs. ^##Isolated gain(1q21) or amp(1q21) defined as ≥ 3 copies of chromosome 1q21 without any other HRCAs. ^ǁǁGain(1q21) or amp(1q21) plus ≥ 1 HRCA defined as ≥ 3 copies of chromosome 1q21 plus ≥ 1 of the following HRCAs: t(4;14), t(14;16), del(17p), and/or t(14;20)

Fig. 5

OS in the ITT population. OS, overall survival; ITT, intent-to-treat; D-VMP, daratumumab plus bortezomib/melphalan/prednisone; VMP, bortezomib/melphalan/prednisone; HR, hazard ratio; CI, confidence interval