scholarly journals Challenges in Implementing NIH Chronic Graft-Versus-Host Disease Diagnosis and Severity Criteria in a Large Multi-Center Prospective Study: Secondary Analysis From the Phase III ATLG Trial

2018 ◽  
Vol 24 (3) ◽  
pp. S197-S198
Author(s):  
Jeanne Palmer ◽  
Frank Glavin ◽  
Mukta Arora ◽  
Robert J. Soiffer ◽  
Navneet S. Majhail ◽  
...  
Keyword(s):  
Prospective Study ◽  
Graft Versus Host Disease ◽  
Secondary Analysis ◽  
Disease Diagnosis ◽  
Phase Iii ◽  
Host Disease ◽  
Graft Versus Host ◽  
Severity Criteria

scholarly journals Comprehensive B Cell Phenotyping Profile for Chronic Graft-versus-Host Disease Diagnosis

2019 ◽  
Vol 25 (3) ◽  
pp. 451-458 ◽  
Author(s):  
Jacob Rozmus ◽  
Amina Kariminia ◽  
Sayeh Abdossamadi ◽  
Barry E. Storer ◽  
Paul J. Martin ◽  
...  
Keyword(s):  
B Cell ◽  
Graft Versus Host Disease ◽  
Disease Diagnosis ◽  
Host Disease ◽  
Graft Versus Host

A randomized, double-blind phase III study of ibrutinib versus placebo in combination with corticosteroids in patients with new onset chronic graft versus host disease.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS7072-TPS7072 ◽  
Author(s):  
David Bernard Miklos ◽  
Madan H. Jagasia ◽  
Hildegard Greinix ◽  
Bor-Sheng Ko ◽  
David A. Jacobsohn ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Response Rate ◽  
Systemic Treatment ◽  
Underlying Disease ◽  
Development Project ◽  
Phase Iii ◽  
Consensus Development ◽  
Double Blind ◽  
Host Disease ◽  
Graft Versus Host

TPS7072 Background: Chronic graft versus host disease (cGVHD) is a common complication of allogeneic stem cell transplantation, with pathophysiology involving alloreactive and dysregulated T and B cells and innate immune populations. Ibrutinib, a first-in-class, once-daily inhibitor of Bruton's tyrosine kinase, is indicated by the US FDA for the treatment of patients (pts) with CLL/SLL. Ibrutinib recently received breakthrough therapy and orphan drug designation for the treatment of pts with cGVHD who did not respond to one or more lines of systemic therapy. Ibrutinib reduces severity of cGVHD in murine models and recently was shown to achieve an NIH-defined overall response rate of 67% in pts with steroid relapsed/refractory cGVHD (Miklos Blood 2016). Methods: The primary objective of this Phase 3, multicenter, international, randomized, controlled, double-blind study is to evaluate the 24-week response rate of ibrutinib versus placebo in combination with prednisone. Pts with newly diagnosed moderate or severe cGVHD, as per NIH Consensus Development Project Criteria (2014), will be randomized in a 1:1 ratio to receive either oral ibrutinib (arm A) or placebo (arm B) in combination with oral prednisone. Ibrutinib or placebo will be given until unacceptable toxicity, relapse of underlying disease, death, or the need for a new systemic treatment for progressive cGVHD. Eligible study pts (age ≥12 yrs) must require systemic treatment with corticosteroids and have no prior systemic treatment for cGVHD. The primary endpoint is response rate (complete or partial response) at 24 weeks, as per NIH Consensus Development Project Criteria, and must occur in the absence of both new therapy for cGVHD and relapse/return of the underlying disease that was the indication for transplant. Secondary endpoints will assess for additional clinical benefit including corticosteroid dose reduction, improvement of Lee cGVHD Symptom Scale scores, withdrawal of all immunosuppressants, and overall survival. This study is currently enrolling pts. Funding source: Pharmacyclics LLC, an AbbVie Company. Clinical trial information: NCT02959944.

CD8 serum levels in acute graft-versus-host disease diagnosis

1994 ◽  
Vol 14 (4) ◽  
pp. 224-228
Author(s):  
Pasqua Bavaro ◽  
Tiziana Bonfini ◽  
Gabriele Di Girolamo ◽  
Antonio Angelini ◽  
Paolo Di Bartolomeo ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Serum Levels ◽  
Disease Diagnosis ◽  
Host Disease ◽  
Graft Versus Host ◽  
Acute Graft

scholarly journals Prospective, Randomized, Double-Blind, Phase III Clinical Trial of Anti–T-Lymphocyte Globulin to Assess Impact on Chronic Graft-Versus-Host Disease–Free Survival in Patients Undergoing HLA-Matched Unrelated Myeloablative Hematopoietic Cell Transplantation

2017 ◽  
Vol 35 (36) ◽  
pp. 4003-4011 ◽  
Author(s):  
Robert J. Soiffer ◽  
Haesook T. Kim ◽  
Joseph McGuirk ◽  
Mitchell E. Horwitz ◽  
Laura Johnston ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
T Lymphocyte ◽  
Graft Versus Host Disease ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Phase Iii ◽  
Double Blind ◽  
Free Survival ◽  
Host Disease ◽  
Graft Versus Host

Purpose Several open-label randomized studies have suggested that in vivo T-cell depletion with anti–T-lymphocyte globulin (ATLG; formerly antithymocyte globulin-Fresenius) reduces chronic graft-versus-host disease (cGVHD) without compromising survival. We report a prospective, double-blind phase III trial to investigate the effect of ATLG (Neovii Biotech, Lexington, MA) on cGVHD-free survival. Patients and Methods Two hundred fifty-four patients 18 to 65 years of age with acute leukemia or myelodysplastic syndrome who underwent myeloablative HLA-matched unrelated hematopoietic cell transplantation (HCT) were randomly assigned one to one to placebo (n =128 placebo) or ATLG (n = 126) treatment at 27 sites. Patients received either ATLG or placebo 20 mg/kg per day on days −3, −2, −1 in addition to tacrolimus and methotrexate as GVHD prophylaxis. The primary study end point was moderate-severe cGVHD-free survival. Results Despite a reduction in grade 2 to 4 acute GVHD (23% v 40%; P = .004) and moderate-severe cGVHD (12% v 33%; P < .001) in ATLG recipients, no difference in moderate-severe cGVHD-free survival between ATLG and placebo was found (2-year estimate: 48% v 44%, respectively; P = .47). Both progression-free survival (PFS) and overall survival (OS) were lower with ATLG (2-year estimate: 47% v 65% [ P = .04] and 59% v 74% [ P = .034], respectively). Multivariable analysis confirmed that ATLG was associated with inferior PFS (hazard ratio, 1.55; 95% CI, 1.05 to 2.28; P = .026) and OS (hazard ratio, 1.74; 95% CI, 1.12 to 2.71; P = .01). Conclusion In this prospective, randomized, double-blind trial of ATLG in unrelated myeloablative HCT, the incorporation of ATLG did not improve moderate-severe cGVHD-free survival. Moderate-severe cGVHD was significantly lower with ATLG, but PFS and OS also were lower. Additional analyses are needed to understand the appropriate role for ATLG in HCT.

Letermovir prophylaxis and cytomegalovirus reactivation in adult allogeneic hematopoietic cell transplant recipients with graft versus host disease.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7004-7004
Author(s):  
Delaney Wolfe ◽  
Qiuhong Zhao ◽  
Emma G Siegel ◽  
Marcin M Puto ◽  
Yvonne Adeduni Efebera ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Hematopoietic Cell ◽  
Competing Risk ◽  
Phase Iii ◽  
Cmv Infection ◽  
Host Disease ◽  
Graft Versus Host ◽  
Clinically Significant ◽  
Cmv Reactivation

7004 Background: Cytomegalovirus (CMV) is the most common clinically significant infection after allogeneic hematopoietic-cell transplantation (allo-HCT) and is associated with increased mortality. The risk for CMV reactivation increases with HLA mismatch, high dose corticosteroids, and graft versus host disease (GVHD). GVHD contributes to significant morbidity and mortality and is treated with immunosuppressive therapies that further increase CMV infection risk. In a phase III trial, letermovir prophylaxis had a lower incidence of CMV infection post-allo-HCT in patients at high risk of CMV reactivation when compared to placebo when given up to day +100. There is a lack of data concerning the effectiveness of letermovir in patients who develop GVHD and may continue letermovir past day +100. Methods: This was a single-center, retrospective study conducted at The Ohio State University. Demographics and transplant details were collected from medical records. The primary outcome was incidence of clinically significant CMV infection (CS-CMVi) within 200 days of allo-HCT. Secondary outcomes included incidence of CMV viremia, duration of letermovir therapy, mortality, and risk factors for CS-CMVi. Early death without CMV was treated as a competing risk for CS-CMVi, while relapse was a competing risk for non-relapse mortality (NRM). Proportional subdistribution or Cox hazards models were used to evaluate the association between use of letermovir and risk of CS-CMVi, NRM, or overall survival (OS) adjusting for potential confounding factors, where use of letermovir and GVHD were treated as time-dependent variables. Results: A total of 262 CMV-seropositive patients who received an allo-HCT between June 1, 2016 and June 30, 2020 were included. Of these, 119 patients received letermovir prophylaxis. A total of 111 patients received treatment for CS-CMVi, which included 82 of 143 (57%) who did not receive letermovir compared to 29 of 119 (24%) who received letermovir. Incidence of CMV viremia was significantly reduced with the use of letermovir in all patients (HR 0.21, 95% CI 0.12–0.34, p < 0.001) and among patients with acute GVHD grade >2 within 200 days post-allo-HCT (HR 0.12, 95% CI 0.05–0.32, p < 0.001), adjusting for age, gender, GVHD prophylaxis and use of ATG or T-cell depleted graft. The median duration of letermovir therapy was 97 days. Nine patients were continued on letermovir indefinitely for recurrent CMV viremia. Patients who received letermovir had decreased NRM (HR 0.41, 95% CI 0.18-0.96, p = 0.04) and improved OS (HR 0.46, 95% CI 0.23-0.95, p = 0.04). Conclusions: Letermovir prophylaxis significantly decreased CS-CMVi and improved NRM and OS in this real-world analysis. In addition, patients with acute GVHD had significantly less CMV viremia, suggesting potential benefit in continuing letermovir prophylaxis in this patient population.

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