ATLL: increased risk of GVHD-related mortality with mogamulizumab administration before Allo-HSCT

Mogamulizumab (mog) administration in adult T-cell leukemia/lymphoma (ATLL) patients is known to deplete T-regulatory cells (T-regs) for many months after allogeneic hematopoietic stem-cell transplantation (allo-HSCT) and can worsen acute graft-versus-host-disease in this specific patient population. This article was written by Shigeo Fuji et al., from the National Cancer Center Hospital, in Tokyo and will be published in Journal of Clinical Oncology in October 2016. They evaluated the safety, efficacy and outcomes achieved upon pretransplantation mog in patients after allo-HSCT.

Key findings of the article have been summarized in this table:

Total number of patients in the study receiving allo-HSCT = 996.

 

No-Mog Group

Mog Group

Median age of patients receiving mog before allo-HSCT

55

61

Patients with data on acute GVHD: No-mog (381/873) vs Mog (47/81) group

Acute GVHD Grade 2/4

43.6%

58%

Acute GVHD Grade 3/4

17.2%

30.9%

Systemic corticosteroids for Acute GVHD

59.8%

73.4%

Refractoriness to systemic corticosteroids Acute GVDH

23.5%

48.9%

Outcomes

Relapse/progression

35.2%

32.3%

1-year OS (overall survival)

49.4%

32.3%*

1-year NRM (non-relapse mortality)

25.1%

43.7%**

GVDH, graft-versus-host-disease

* Pretransplantation mog=significant risk factor for OS

**Pretransplantation mog= significant risk factor for NRM

 

Outcomes of patients (mog group)

 

Interval between last mog administration and Allo-HSCT  ≥50 days

Interval between last mog administration and Allo-HSCT <50 days

 

n=38

n=42

1-year NRM

34.4%

55.1%*

1-year OS

44.1%

20.2%**

* Interval between last mog administration and Allo-HSCT <50 days=High risk of NRM

** Interval between last mog administration and Allo-HSCT <50 days=Poor OS

Conclusions:

Administration of mog before allo-HSCT in patients demonstrated worsening effects on patient outcomes (significant risk factor for OS and NRM) in the current study. Furthermore, studies need to better select patients undergoing this treatment option in future.

Pretransplantation Anti-CCR4 Antibody Mogamulizumab Against Adult T-Cell Leukemia/Lymphoma Is Associated With Significantly Increased Risks of Severe and Corticosteroid-Refractory Graft-Versus-Host Disease, Nonrelapse Mortality, and Overall Mortality

Abstract
Purpose

Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is one important treatment option for patients with aggressive adult T-cell leukemia/lymphoma (ATLL). Mogamulizumab (anti-CCR4 monoclonal antibody; Mog) was recently approved as a treatment for ATLL in Japan. Major concerns exist about the possible adverse effects of pretransplantation Mog because Mog depletes regulatory T cells for several months. We assessed the impact of pretransplantation Mog on clinical outcomes after allo-HSCT.

Patients and Methods

We included 996 allo-HSCT recipients age 70 years or younger with aggressive ATLL who were given the diagnosis between 2000 and 2013 and who received intensive chemotherapy by multiple chemotherapeutic drugs as first-line therapy. Before allo-HSCT, 82 patients received Mog with a median interval of 45 days from the last Mog to allo-HSCT.

Results

Pretransplantation Mog was associated with an increased risk of grade 3 to 4 acute graft-versus-host disease (GVHD; relative risk, 1.80; P<.01) and refractoriness to systemic corticosteroid for acute GVHD (relative risk, 2.09; P<.01). One-year cumulative incidence of nonrelapse mortality was significantly higher in patients with pretransplantation Mog compared with those without (43.7% v 25.1%; P<.01). The probability of 1-year overall survival was also significantly inferior in patients with pretransplantation Mog compared with those without (32.3% v 49.4%; P<.01). In particular, use of Mog with intervals<50 days to allo-HSCT was associated with a dismal clinical outcome.

Conclusion

Pretransplantation Mog was significantly associated with an increased risk of GVHD-related mortality, which supports the relevance of CCR4-expressing Tregs after allo-HSCT in humans. In clinical practice, Mog should be cautiously used for patients with ATLL who are eligible for allo-HSCT.

Reference:
  1. Fuji S. et al.,  Pretransplantation Anti-CCR4 Antibody Mogamulizumab Against Adult T-Cell Leukemia/Lymphoma Is Associated With Significantly Increased Risks of Severe and Corticosteroid-Refractory Graft-Versus-Host Disease, Nonrelapse Mortality, and Overall Mortality. J Clin Oncol 2016; 34:3426-33.