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A phase III trial of omidubicel versus standard umbilical cord blood for improved stem cell engraftment

Mar 19, 2021
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Advantages of allogenic transplantation with umbilical cord blood (UCB) stem cells over bone marrow stem cells include ease of collection and reduced stringency for HLA matching, which is a particular benefit for patients who do not have access to a matched donor. However, a major limitation of UCB is the low stem cell dose available for transplantation. An option to increase cell dose is to perform ex vivo expansion of the cord blood stem cells before transplantation. Omidubicel is a nicotinamide-based technology which combines expanded UCB stem cells with differentiated immune cells, including T cells.

The results of the phase III trial (NCT02730299) evaluating the safety and efficacy of transplantation with omidubicel compared with standard UCB were presented by Mitchell Horwitz during the 2021 Transplantation and Cellular Therapy Meetings of ASTCT and CIBMTR.1 Here, we are pleased to provide a summary of these results.

Study design

This phase III open-label, randomized, multicenter study compared the safety and efficacy of omidubicel with standard myeloablative UCB transplantation in patients with hematologic malignancies.

Inclusion criteria:

  • Age 12−65 years
  • High-risk hematologic malignancy
  • Eligible for allogeneic bone marrow transplantation
  • No HLA-matched donor

Patient disposition:

  • A total of 125 patients were enrolled
  • The intent-to-treat (ITT) population for the omidubicel arm consisted of 62 patients; 52 were transplanted as per protocol (defined as ‘as treated’ [AT])
  • Of the 63 ITT patients in the control (standard UCB) arm, 56 were in the AT population
  • Patients were stratified by treatment center, disease risk index, age, and intent to perform single vs double cord transplant in the control arm

The primary endpoint was time to neutrophil engraftment, and secondary endpoints were platelet engraftment, incidence of infections, and days out of hospital within the first 100 days after transplantation. Other analyses included incidence of acute and chronic graft-versus-host disease (GvHD), nonrelapse mortality, relapse, disease-free survival, and overall survival.

Results

The demographics for patients in the omidubicel and control arms of the ITT population were well balanced. Selected patient and transplant characteristics are shown in Table 1.

Table 1. Selected ITT patient and transplant characteristics1

Characteristic

Omidubicel arm
(n = 62)

Control arm
(n = 63)

Female, %

48

37

Median age, years (range)

40 (13–62)

43 (13–65)

Disease, %
              AML
              ALL

              MDS

              CML

              Lymphoma

              Rare leukemia

 
44

32

10

7

5

3


52

33

5

3

3

3

Myeloablative conditioning regimen, %
              Thiotepa, busulfan, fludarabine

              TBI 1,320 cGy, fludarabine, cyclophosphamide

              TBI 1,350 cGy, fludarabine, thiotepa

              Transplanted off-study

 
44

39

11

6


44

33

14

8

HLA match, %

              4/6

              5/6

              6/6

 

74

24

2

 

73

25

2

Intended CBU transplant, %

              Single

              Double

 

32

68

 

33

67

ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; CBU, cord blood unit; CML, chronic myeloid leukemia; HLA, human leukocyte antigen; MDS, myelodysplastic syndromes; TBI, total body irradiation.

Graft characteristics

  • There was a median 133-fold increase in CD34+ cells in the omidubicel product, compared with preexpansion UCB, providing a median of 6.6 × 108 CD34+ cells in total, and a CD34+ cell dose of 9.0 × 106 cells/kg
  • In contrast, patients randomized to the control arm received a median CD34+ cell dose of 0.3 × 106 cells/kg

Primary endpoint: neutrophil engraftment

  • In the ITT and AT populations, median time to neutrophil engraftment was significantly shorter for the omidubicel arm, compared with the control arm (p < 0.001, Table 2)
  • Cumulative incidence of neutrophil engraftment at Day 42 was greater for patients receiving omidubicel than for those receiving standard UCB (Table 2)

Table 2. Effect of omidubicel on time to and incidence of neutrophil engraftment1

Primary endpoint

Omidubicel arm

Control arm

p value

Median time to neutrophil engraftment, days (95% CI)

              ITT population

              AT population

 

 

12.0 (10.0–15.0)

10.0 (8.0–13.0)

 

 

22.0 (19.0–25.0)

20.5 (18.0–24.0)

 

 

< 0.001

< 0.001

Cumulative incidence of neutrophil engraftment at Day 42 (AT), %

96

89

NR

AT, as treated; ITT, intent to treat; NR, not reported.

Secondary endpoints

All secondary endpoints showed a significant improvement for patients in the omidubicel arm, compared with the control arm (Table 3).

Table 3. Secondary endpoint results1*

Secondary endpoint

Omidubicel arm

Control arm

p value

Median time to platelet engraftment (AT), days

37

50

0.023

Cumulative incidence of platelet engraftment, %

              ITT population at Day 42

              AT population at Day 100

 

 

55

83

 

 

35

73

 

 

0.028

NR

Incidence of Grade 2–3 bacterial or invasive fungal infections by Day 100

37

57

0.027

Incidence of viral infections by Day 100

10

26

NR

Median days alive and out of hospital

60.5

48.0

0.005

AT, as treated; ITT, intent to treat; NR, not reported.

*Results are for ITT population unless specified otherwise.

Exploratory endpoints

There was no difference in the incidence of chronic or acute GvHD between patients in the omidubicel or control arm. Visit the GvHD Hub for a further discussion of these results by Mitchell Horwitz.

A trend to reduced incidence of nonrelapse mortality was seen for the omidubicel arm compared with the control arm (p = 0.09); however, there was no significant difference in relapse, or disease-free or overall survival, although it should be noted that the study was not powered to evaluate these endpoints.

Conclusion

In this phase III study, patients transplanted with omidubicel achieved faster hematopoietic recovery, fewer early infections, and fewer days in hospital, compared with patients receiving standard UCB. No excessive toxicity was observed, and there was no difference between arms in the incidence of chronic or acute GvHD. It was proposed that omidubicel be considered a new standard of care for patients eligible for UCB transplantation.

  1. Horwitz M, Cutler C, Stiff P, et al. Improved clinical outcomes with omidubicel versus standard myeloablative umbilical cord blood transplantation: Results of a phase III randomized, multicenter study. Transplantation and Cellular Therapy. 2021;27(Issue 3, Supplement):S33-S34. DOI: 1016/S2666-6367(21)00060-9

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