Table 4:

Notable studies examining busulfan and melphalan plus/minus bortezomib in the literature

Reference	Study Design	Comparator	Response	Progression free survival	Toxicity
Blanes et al26, Annals of hematology 2019	Phase II multi-institution, Spain; 1:2 matched control analyses	BuMel* v Mel200	No difference: BuMel v Mel200 ORR: 82 v 91%	Median PFS: 33 v 24m (p=0.04)	TRM: 4% in BuMel v 2% in control No grade III/IV mucositis in BuMel
Park et al, BBMT 2019	Phase I/II multicenter trial, Korea	No comparator BuMelVel**	At day 90: ≥VGPR: 75% CR: 55%	Median PFS: 26.8m	Grade 3 mucositis: 14.6%
Bashir et al, Lancet Haematol 2019	Phase III single institution, MD Anderson Cancer Center	BuMel*** v Mel200	No difference at day 100 BuMel v Mel: MRD negative: 58 v 61% CR: 52 v 49%	Median PFS: BuMel 64.7m v Mel 43.5m (p=0.022)	Grade 3–4 non-haematological: BuMel (84%) v Mel (33%) (p<0.0001) Grade 3 Mucositis: BuMel 14% v Mel 0% (p<0.0001)
Jung et al, BBMT 2018	Phase II multicenter, Korea	No comparator BuMel#	ORR: 94% 43.5% sCR 27.3% VGPR	Median PFS: 27.2m	Grade 3–4 mucositis 15.2% 3 patients (3.2%) developed SOS
Byun et al27, Blood Research 2018	Korean National Health Database, retrospective comparison	BuMel## v HDMel	Non-reported	Improved 3-year PFS in the BuMel group: 70.3 v 52.5% (P-0.043)	No differences (mucositis not specifically reported)
Rosinol et al, ASH 2017	Phase III national multicenter, Spain	BuMel### v Mel200	Per high dose arm, pending	Per high dose arm, pending	Per high dose arm, pending
Barta et al28, CLML 2017	Phase II multi-institution, US	No comparator BuMelVel ŧ	ORR 100% at day 100	2-year PFS 59% (95%CI 38–89%)	53% grade 3 or 4 mucositis

^*(Blanes et al): BuMel: intravenous Busulfan at 3.2mg/kg daily over days −5 to −3

^**(Park et al) BuMelVel: intravenous busulfan (i.v., 3.2 mg/kg/day from days −5 to −3); melphalan (i.v.,140 mg/m2/day on day −2), bortezomib i.v. 1.3mg/m2 on days −6, −3, and +1

^***(Bashir et al) BuMel: Busulfan test dose followed by pharmacokinetically adjusted doses of Busulfan on days −7, −6, −5, and −4 to achieve a target daily area under the curve (AUC) of 5000 mmol-minute and melphalan 70 mg/m² per day on days −2 and −1; melphalan 70mg/m2 on days −2 and −1

^#(Jung et al) BuMel: intravenous busulfan of 3.2 mg/kg was administered over 3 hours once daily from day −6 to days −4; melphalan of 70 mg/m2/day was administered on day −3 and day −2

^##(Byun et al) BuMel: Dosing not reported

^###(Rosinol et al) BuMel: intravenous busulfan at 9.6mg/kg; melphalan 140mg/m²

^ŧ(Barta et al) BuMelVel: intravenous PK directed Busulfan to achieve target total AUC of 20,000 from days −6 to −3; melphalan 150mg/m2 onf day −2; intravenous Bortezomib given at 1mg/m² on days −6,−3,+1,+4

M: months

TRM: Transplant-related mortality

PFS: Progression free survival

HDMel: High dose melphalan, melphalan at 200mg/m2 or less

sCR: stringent complete response

VGPR: very good partial remission

SOS: sinusoidal obstructive syndrome