Cytotect®CP as salvage therapy in patients with CMV infection following allogeneic hematopoietic cell transplantation: a multicenter retrospective study.

International audienceCytomegalovirus is one of the main contributing factors to high mortality rates in patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT). The main factors of treatment failure are both drug resistance and intolerance. In some cases, Cytotect(R)CP CMV-hyperimmune globulin is used as salvage therapy. This study aims to investigate the safety and efficacy of Cytotect(R)CP as a salvage therapy in patients with CMV infection after allo-HCT. Twenty-three consecutive patients received Cytotect(R)CP for CMV infection after prior CMV therapy. At the time of Cytotect(R)CP introduction, 17 patients (74%) had developed acute GVHD and 15 patients (64%) were receiving steroid treatment; Cytotect(R)CP was used as monotherapy (n = 7) and in combination (n = 16). Overall, response was observed in 18 patients (78%) with a median time of 15 days (range: 3-51). Of the 18 responders, 4 experienced CMV reactivation, while 5 responders died within 100 days of beginning treatment. Of these 5 deaths, 4 were due to causes unrelated to CMV. Estimated 100-day OS from the introduction of Cytotect(R)CP was 69.6%. No statistically significant difference was observed in 100-day OS between responders and non-responders (73.7% vs 50.0%, p = 0.258). Cytotect(R)CP as salvage therapy is effective and well-tolerated. Given its safety profile, early treatment use should be considered

Extracorporeal photopheresis as first line strategy in the treatment of acute graftversus-host disease after haematopoietic stem cell transplantation: a single centre experience

International audienceBackground aims: Corticosteroids are the standard first-line treatment for acute graft-versus-host disease (aGVHD), but they are associated with many complications, and less than half of patients have a sustained response.Methods: To improve outcomes, we performed a retrospective study to analyze the efficacy of the addition of extracorporeal photopheresis (ECP) to low-dose corticosteroids in 37 adult patients (median age, 57 years) with skin-predominant aGVHD (grade I, n = 17; grade II, n = 18; and grade III, n = 2). All patients received ECP in combination with 1 mg/kg prednisone (n = 26) or topical steroids (n = 11).Results: Overall response rate was 81% after a median of three ECP procedures (range, 2–8), including 22 complete responses (CR, 59%) and eight very good partial responses (VGPR, 22%). The 11 patients treated with topical corticosteroids achieved CR. Furthermore, 16 (62%) patients reached prednisone withdrawal at a median of 100 days (range, 42–174 days) after its initiation. Eighteen patients developed chronic GVHD (cGVHD); 11 of them (who were in CR of aGVHD) had a new-onset cGVHD, and seven experienced progressive cGVHD (five non-responding and two VGPR patients). A second-line immunosuppressive treatment was initiated in only five (14%) non-responding patients. With a median follow-up of 31 months (range, 6–57 months) 2-year overall survival and non-relapse mortality were 74% and 11%, respectively.Conclusions: Overall, the combination of low-dose corticosteroids and ECP appear to be safe and effective for first-line treatment of skin predominant aGVHD

Pooled Fecal Allogenic Microbiotherapy for Refractory Gastrointestinal Acute Graft-Versus-Host Disease : Results from Early Access Program in Europe

International audienceIntroduction Acute Graft-versus-host disease (aGvHD) is a major source of mortality following allogeneic hematopoietic cell transplantation (allo-HCT). Fecal microbiotherapy has shown promising results in several pilot studies in patients with refractory gastrointestinal (GI)-aGvHD. Here we report clinical outcomes from 111 patients diagnosed with steroid-refractory (SR) or dependent (SD) GI-aGvHD treated with the pooled allogeneic microbiotherapy MaaT013 as part of the Early Access Program (EAP) in Europe. Patients and methods One hundred and eleven patients (including 1 pediatric patient aged 15 years) with SR/SD GI-aGvHD (Classical n=70, late onset n=12, overlap syndrome n=16, hyper-acute n=13) were treated with MaaT013 therapy as part of Early Access Program in Europe (France and Germany). These patients had previously failed 1 to 6 systemic GvHD treatment lines (median 3; 94/111 received ruxolitinib). Most patients had grade III to IV aGvHD (9% grade II, 49% grade III aGvHD, 42% grade IV). For each patient, a total of 3 MaaT013 administrations were planned every 7 +/- 2 days (median dose administered 3). Each dose is composed of 30 g of feces in 150 mL of suspension from 4 to 8 healthy donors administered by enema (except for 1 patient by nasogastric tube). Treatment response was calculated among all treated patients based on aGvHD staging and grading at day 28 (D28) at the time of the EAP request. Results At D28, the GI-ORR was 53%: 39 CR (35%), 15 VGPR (14%), 5 PR (5%). GI-ORR was higher in patients with lower grade aGvHD (100% in grade II, 63% in grade III, 32% in grade IV) and higher in SD versus SR (88% versus 47%). Overall response considering all organs (n=108 with 3 missing data) was 50%, including 34 CR, 16 VGPR and 4 PR. Administration of MaaT013 in the pediatric patient was well tolerated and led to complete response of GI and skin symptoms (the patient had stage 3 skin and stage 4 GI aGvHD) up to 12 months. Symptoms of the liver were not resolved at D28 (stage 2 liver, stable disease) but improved from month 6 without additional therapy. Overall survival (OS) was 56% at 6 months (M6) and 47% at M12 . The median follow-up among surviving patients was 355 days (range, 27-731).OS was significantly higher in patients achieving at least GI-PR at D28 (Responder, R; n=59) compared to patients in treatment failure (Non-responder, NR; n=52): 74% versus 36% at M6, 67% versus 24% at M12 (p<0.0001 log-rank test) . Median survival duration in R was 293 days versus 56 days in NR. Interestingly, in the subgroup of 38 patients previously treated with ruxolitinib as 2 nd line and MaaT013 as 3 rd line GI-ORR was improved being 61% D28, with 58% CR. OS at M6 was 55% and 52% at M12. OS was significantly higher in R patients, when compared to NR patients (81% versus 16% at M6 and 81% versus 8% at M12 for R and NR respectively, p<0.0001 log-rank test). MaaT013 displays a good overall safety profile in EAP population: 29 pharmacovigilance cases were reported in 27 patients, including 18 cases that could be possibly considered related to MaaT013 either by the physician or the company: sepsis in 5 patients, bacteremia in 7 patients, rectal bleeding/ anorectal disorder in 3, C. difficile colitis in 1, E. coli osteoarthritis in 1, detection of G. silvicola in stools in 1. No pathogen transmission has been reported. In 2 patients, non-pathogenic commensal bacteria isolated following infectious events were detected in the administered MaaT013 batch. Causality could not be formally excluded in these cases. 56 deaths have been reported. The cause of death was GvHD in 23 patients, severe infection in 15, relapse of underlying malignancy in 9, COVID-19 in 5, hemorrhage during surgery in 1, neurological complications post allo-HCT in 1, and cardiac arrest in 2 patients. No causality link with MaaT013 administration has been identified. Conclusion Overall, EAP clinical data showed that MaaT013 was safe and effective for the treatment of SR/SD-GI-aGvHD especially in patients having previously received ruxolitinib. Interestingly, response of GI-aGvHD correlates with increased overall survival, suggesting a strong favorable benefit-risk profile for MaaT013. A Phase 3 trial is currently ongoing to confirm these results in ruxolitinib-refractory patients (NCT04769895)