IMW 2019 | MRD-negativity after tandem autologous-allogeneic HSCT with bortezomib maintenance

During the 17^th International Myeloma Workshop (IMW), in Boston, MA, US, a ‘Myeloma Transplant and Maintenance Strategies’ session was held on Saturday 14^th September 2019. In this session, Richard LeBlanc from the Hôpital Maisonneuve-Rosemont, University of Montreal, Montreal, CA presented results of a phase II clinical trial using bortezomib in the post allo-SCT maintenance regimen.¹

As part of the phase II clinical trial (NCT02308280) LeBlanc and the team aimed to determine whether the addition of maintenance bortezomib (V) to tandem autologous- and allogeneic- (allo-) stem cell transplantation (SCT) would reduce relapse rates and chronic graft-versus-host disease (cGvHD) in patients with high-risk (HR) newly diagnosed multiple myeloma (NDMM). They also aimed to determine the value of bone marrow measurable residual disease (MRD) assessment to determine the progression of the disease.

Study design and results:

• Inclusion criteria:
  • NDMM with measurable disease
  • Aged < 65 with ISS of III, a diagnosis of plasma cell leukemia, and/or cytogenetics associated with poor outcome
  • Aged ≤ 50 regardless of other risk factors
  • Matched related (MRD) or unrelated donor (URD)
• Participant treatment regimen:
  • V induction
  • Autologous SCT, high dose melphalan 200 mg/m²
  • Non-myeloablative allo-SCT
  • V 1.3 mg/m² subcutaneously every two weeks for twelve months
• Patient characteristics (Table 1)

Table 1: Patient characteristics

Abbreviations: ISS; international staging system, CyBorD; cyclophosphamide/bortezomib/dexamethasone, VTdD; Bortezomib/thalidomide/dexamethasone, MUD; matched unrelated donor, HCT-CI; Hematopoietic cell transplantation - specific comorbidity index
Patient characteristics		%
Age, median years (range)	54 (35—64) ≤ 50	41
Sex	Male Female	54 46
ISS	I II III Unknown	15 36 41 8
Cytogenetics (n= 34)	t(4:14) t(14:16) t (14:20) del 17p Gain 1q del 1p ≥ 2 adverse cytogenetics Any high-risk adverse cytogenetics	15 0 0 6 24 3 18 65
Induction	CyBorD VTdD	82 18
Number of induction cycles	Median four Range 4 — 7
Maintenance	Lenalidomide	13
Comorbidity index (HCT-CI)	0 1 2 3	49 15 21 15
Donors	Sibling MUD	41 59

• Responses were determined according to the International Myeloma Working Group (IMWG) guidelines² (Table 2)

Table 2: Response rates after treatment phases

Abbreviations: CR; complete response, VGPR; very good partial response, PR; partial response, SD; stable disease, PD; progressive disease
	Induction (n= 39)	After ASCT (n= 39)	After allo-SCT (n= 39)	During V (n= 38)	After V (n= 31)
	%
≥ CR	NE	56	64	77	61
VGPR	72	36	23	8	3
PR	28	8	5	0	0
SD	0	0	0	0	0
PD	0	0	8	16	35

• Overall survival (OS) at two years was 92% (95%CI 77 — 97)

• Progression-free survival (PFS) at two years was 67% (95%CI 49 — 80)

• Three patients died (one from the progression of myeloma, and two from GvHD/infection)

• Myeloma progression was noted in 14 patients

• On MRD assessment, < 50 cells were associated with a cumulative incidence of progression at two years of 27%, and ≥ 50 cells, an 82% cumulative incidence of progression at two years

• In terms of V safety, side-effects included diarrhea (n= 1), hemorrhagic cystitis (n= 3) and brain infection (n= 2)

• Grade II—IV acute GvHD (aGvHD) was observed in 26% at 12 months (95% CI 13 — 40) and moderate/severe cGvHD was observed in 46% at 24 months (95% CI 29—61)

  • When compared with a historical control, there was a significant reduction in all grades (85 vs 56%, p= 0.0002) and of moderate/severe (69 vs 46%, p= 0.008) cGvHD, and a non-significant reduction in severe cGvHD (26 vs 11%, p= 0.065) with the addition of V

LeBlanc concluded that adding V into the post allo-SCT maintenance regimen is safe and may reduce cGvHD development and severity. They also found that low MRD six months after V is related to improved outcomes. He added that longer-term follow-up was needed to evaluate the curative ability of this regimen.