Combining therapeutic antibodies using basiliximab and etanercept for severe steroid-refractory acute graft-versus-host disease: A multi-center prospective study

Abstract

Acute graft versus host disease (aGVHD) remains a major problem after allogeneic hematopoietic stem cell transplantation. Standard frontline therapy for aGVHD involves corticosteroids. However, fewer than half of patients have a lasting complete response. The long-term mortality rate of steroid-refractory aGVHD (SR-aGVHD) remains around 70%. To date, no consensus has been reached regarding the optimal salvage treatment for SR-aGVHD. We performed the first prospective, multi-center clinical trial to assess the efficacy and safety of a novel approach to treat severe (grades III-IV) SR-aGVHD with the combination of basiliximab and etanercept. Sixty-five patients with severe SR-aGVHD from six centers were included. The median number of basiliximab infusions was 4 (range 2-11) and of etanercept was 9 (range 2-12). At day 28 after starting the combination treatment, overall response (complete and partial response: CRCPR) to second-line treatment was 90.8% with 75.4% being CR. The incidences of CR per organ were 100%, 73.8%, and 79.7% for skin, liver, and gut involvement, respectively. Patients >30-y old (p D 0.043, RR D 3.169), development of grades III-IV liver aGVHD (p D 0.007, RR D 5.034) and cytomegalovirus (CMV) reactivation (p D 0.035, RR D 4.02) were independent predictors for incomplete response. Combined treatment with basiliximab and etanercept resulted in improved CR to visceral aGVHD and significantly superior 2-y overall survival (54.7% vs. 14.8%, p <0.001) compared with classical salvage treatments. Our data suggest that the combination of basiliximab and etanercept may constitute a promising new treatment option for SR-aGVHD.

Ruxolitinib combined with etanercept induce a rapid response to corticosteroid‐refractory severe acute graft vs host disease after allogeneic stem cell transplantation: Results of a multi‐center prospective study

“…10 Previously, we have treated severe (grades III-IV) SR-aGVHD with the combination of basiliximab and etanercept. 11 Although the overall response rate (ORR) was satisfactory (complete and partial response: 90.8%), infections, especially invasive fungal infections, were the major complications in this cohort. Furthermore, the cost of the combination of basiliximab and etanercept is relatively high, which urges us to seek a better second-line treatment regimen.…”

Improved survival after LTx-associated acute GVHD with mAb therapy targeting IL2RAb and soluble TNFAb: Single-center experience and systematic review

“…The incidence of GVHD is between 20% and 70%. Due to the high incidence of GVHD after hematopoietic stem cell transplant, mAb therapy has been introduced with better response rates compared with steroids or to treat steroid‐refractory acute GVHD …”

Treatment and unmet needs in steroid-refractory acute graft-versus-host disease

“…The ORR at day 28 was 91%; 75% of patients had a CR. The 2-year OS rate was 55% [22], suggesting that combination therapy may further improve outcomes in patients with SR-aGVHD. However, this clinical benefit may be limited to basiliximab plus etanercept, given that a retrospective study of combination therapy with inolimomab plus etanercept only showed an ORR of 48% at day 28 and a 2-year OS of 10% [71].…”

“…A deeper understanding of the pathophysiology of aGVHD has already resulted in the development of targeted therapies, and new findings may lead to the development of even more. For instance, some therapies target T-cell activation by using antibodies against the IL-2 receptor (IL-2R) [21], whereas others target the third phase of aGVHD, using antibodies against various markers on T lymphocytes [22]. A number of studies also demonstrated that gut microbiota dysbiosis is associated with SR-aGVHD [23][24][25][26][27].…”

“…Basiliximab in combination with etanercept was assessed in a prospective, multicenter clinical trial of 65 patients with severe (grades III-IV) SR-aGVHD [22]. The ORR at day 28 was 91%; 75% of patients had a CR.…”