aGvHD,   cGvHD

EBMT 2019 | Begelomab: an anti-CD26 monoclonal antibody for the treatment of steroid-refractory GvHD

The treatment of SR-GvHD remains a large area of unmet need as current options are limited. Begelomab targets the T-cell activation antigen CD26 thereby preventing migration of T-cells and may present a new treatment option for patients with GvHD.

On Tuesday 26 March 2019, during the 45th Meeting of the European Society for Blood and Marrow Transplantation (EBMT) in Frankfurt, Germany, Andrea Bacigalupo from Fondazione Policlinico Universitario Agostino Gemelli, Rome, IT, presented the outcomes from 69 patients who received begelomab, an anti-CD26 monoclonal antibody (MoAB), for the treatment of steroid-refractory graft-versus-host disease (SR-GvHD).1

Background

CD26 has a co-stimulatory effect and regulates the activity of hormones, neuropeptides and chemokines. It is highly expressed on T-cells migrating through endothelial cell monolayers and inhibiting CD26 prevents this migration in vivo. In humans, the T-cells that infiltrate the gut and skin are CD26+. These factors have made CD26 an attractive target for monoclonal antibody (MoAB) therapy for GvHD treatment.

The results presented show the outcomes of 69 patients who received begelomab as part of pilot studies and a multicenter compassionate use follow-up program.

Study design and patient characteristics
  • Patient eligibility:
    • Adult (18–70) patients
    • Presenting with SR-GvHD that progressed during first or second line treatment, or did not respond on day +5 of treatment with 2 mg/kg of methylprednisone + cyclosporine A (early identification of steroid refractoriness)
  • The safety and efficacy of begelomab was tested in two cohorts; the first was a series of two pilot studies (n = 28) and the second was a compassionate use follow-up study (n = 41).
  • In total, data from 69 patients is available (patient characteristics shown in Table 1)
  • Details on the two pilot studies:
    • EUDRACT 2007-005809-21: dose 2 mg/day for 5 days
    • EUDRACT 2012-001353-19
      • Dose finding: 2 mg/m2/day or 3 mg/m2/day or 4.5 mg/m2/day for 5 days
      • Dose extending: 3 mg/m2/day on days 1–5, then twice weekly on days 8, 11, 15, 18, 22 and 25

Table 1: Patient characteristics (pilot study and follow-up study)1

 

Pilot

Follow-up

N

28

41

Median age

42 (20–66)

44 (3–70)

Lines of prior failed treatment

-          1

-          2

-          3

-          4

 

28

0

0

0

 

18

11

11

1

Stem cell source

-          Bone marrow

-          Peripheral blood

-          Cord blood

 

79%

21%

0%

 

34%

63%

3%

GvHD grade III–IV (total)

-          Skin grade III–IV

-          Liver grade III–IV

-          Gut grade III–IV

75%

57%

21%

29%

98%

49%

68%

26%

Safety:

In this cohort, no adverse events (AEs) including severe AEs related to the treatment were reported. Treatment with begelomab had no effect on the peripheral blood cell count and did not increase the risk of infection.

Efficacy
  • The full response rates for non-relapse mortality (NRM), overall survival (OS) and response by GvHD type and grade, as presented by Professor Bacigalupo, are shown in Table 2.
  • Overall survival in responders vs non-responders at day +28:
    • Responders (n = 47): 75%
    • Non-responders (n = 22): 31%

Table 2: Response, NRM and OS rates to begelomab1

 

Pilot group (n = 28)

Follow-up group (n = 41)

Response at day +28

75%

63%

Response at day +28 with:

-          Grade II GvHD

-          Grade III GvHD

-          Grade IV GvHD

 

57%

83%

67%

 

Not evaluable

80%

56%

NRM at 6 months

28%

39%

OS at 1 year

50%

33%

Response on day + 28 by GvHD

-          Skin grade III–IV

-          Liver grade III–IV

-          Gut grade III–IV

                                

68%

67%

87%

                                                                     

67%

57%

54%

Conclusion

An overall response rate of 68% on day +28 was achieved in this study, indicating begelomab has a significant effect, including in patients with grade III and grade IV liver and gut SR-GvHD.

Ongoing studies using this novel drug include a phase I/II trial using begelomab as first-line treatment for grade II or above aGvHD in combination with standard steroid therapy (2017-002715-34).

References
  1. Bacigalupo A. et al. Treatment of steroid resistant acute graft versus host disease with an anti-CD26 monoclonal antibody – begelomab. Abstract OS7-6. 2019 March 26. 45th Annual Meeting of the European Society of Blood and Marrow Transplantation (EBMT), Frankfurt, DE
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