Tocilizumab as first-line therapy for steroid-refractory acute graft-versus-host-disease: analysis of a single-center experience

2019 ◽  
Vol 60 (9) ◽  
pp. 2223-2229 ◽  
Author(s):  
Filiz Yucebay ◽  
Christina Matthews ◽  
Marcin Puto ◽  
Junan Li ◽  
Basem William ◽  
...  
Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4532-4532
Author(s):  
Surbhi Singhal ◽  
Theresa Brondstetter ◽  
David B. Miklos ◽  
Debra Kate Tierney ◽  
Joe Hsu ◽  
...  

Introduction: Chronic graft-versus-host disease (cGVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation. Pulmonary cGVHD consists of both obstructive and restrictive pulmonary changes, and as such, represents a broad spectrum of disease. While corticosteroids are a mainstay of treatment, there is no established standard-of-care for second line therapy. The Bruton's tyrosine kinase inhibitor ibrutinib was recently approved for treatment of cGVHD after failure of 1 or more lines of systemic therapy. However, the role of ibrutinib in patients with pulmonary cGVHD is not well understood. Here we report an institutional experience of ibrutinib as non-first-line therapy for pulmonary cGVHD. Methods: We performed a retrospective study of adult patients with steroid-dependent or steroid-refractory pulmonary cGVHD treated with ibrutinib as non-first line therapy between 2014 and 2018. Patients were diagnosed with pulmonary cGVHD if they met the 2014 National Institutes of Health cGVHD Consensus Panel criteria or were diagnosed based on expert opinion. All patients received appropriate GVHD prophylaxis at the time of transplant. The severity of pulmonary cGVHD was assessed by pulmonary function testing (PFT) done prior to and 180 days after initiation of ibrutinib therapy. The primary clinical outcome was absolute change in the percentage of predicted forced expiratory volume in 1 second (%FEV1) over 180 days. Patients were identified as having a complete response (normalization of %FEV1), partial response (≥10% increase in %FEV1), stable disease (<10% change in %FEV1), or progression (≥10% decrease in %FEV1). Results: A total of 17 patients received ibrutinib for pulmonary cGVHD (mean age 46 ± 11 years, 59% male), with a mean duration of 34 ± 17 weeks from transplant to diagnosis of cGVHD (31% de novo, 31% progressive, 38% interrupted). On average, patients had 5 involved organs, received 4 treatments for cGVHD prior to ibrutinib, and 14/17 (82%) were on at least 0.25 mg/kg/day of prednisone (or an equivalent dose of corticosteroid) at the time of ibrutinib initiation. The median %FEV1 at time of ibrutinib initiation was 50 ± 24%. At 180 days after initiation, 14/17 patients (82%) continued receiving ibrutinib (1 patient each discontinued therapy for lack of symptomatic improvement, oral ulcers, and enrollment in a clinical trial). Among the 14 patients who completed 180 days of therapy, only 3 had disease progression (Figure 1). Conclusions: Ibrutinib was generally well tolerated as a non-first line therapy for pulmonary cGVHD. In this cohort of patients with steroid-dependent or steroid-refractory disease who had progression on multiple lines of therapy, most had stable or improved pulmonary function by %FEV1 while on ibrutinib. Given the heterogeneity of pulmonary cGVHD, further studies can help clarify which patients are most likely to demonstrate response. Disclosures Miklos: Becton Dickinson: Consultancy; Adaptive Biotechnologies: Consultancy, Research Funding; Pharmacyclics: Consultancy, Patents & Royalties, Research Funding; Celgene-Juno: Consultancy; AlloGene: Consultancy; Janssen: Consultancy; Precision Bioscience: Consultancy; Kite, A Gilead Company: Consultancy, Research Funding; Miltenyi: Consultancy, Research Funding; Novartis: Consultancy.


PLoS ONE ◽  
2017 ◽  
Vol 12 (10) ◽  
pp. e0187184 ◽  
Author(s):  
Cornelis N. De Jong ◽  
Lotte Saes ◽  
Clara P. W. Klerk ◽  
Marjolein Van der Klift ◽  
Jan J. Cornelissen ◽  
...  

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4206-4206
Author(s):  
Silvia Finotto ◽  
Dario Marino ◽  
Caterina Boso ◽  
Filippo Marino ◽  
Luca Canziani ◽  
...  

Abstract DLBCL is the most common type of non-Hodgkin lymphoma and it usually affects elderly patients, with a median age at diagnosis of 70 years and an incidence that rises with increasing age. Nevertheless patients > 70 years are rarely included in clinical trials and the management is often different according to local practice. A pre-treatment evaluation based on Performance Status (PS) or comorbidity index is not sufficient to identify patients suitable for treatment with curative intent. We retrospectively reviewed 93 patients with newly diagnosed DLBCL, ≥65 years old , treated from January 2009 to December 2015 at Veneto Institute of Oncology-IRCCS (median age 76 years, range 65-96). Twenty-eight patients (28) were older than 80 years. All but one received at least first line treatment. All patients were evaluated with CGA at diagnosis, based on Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL) and Cumulative Illness Rating Scale (CIRS). According to these variables they were classified into three categories named 'fit', 'vulnerable' and 'frail'. In addition, a cancer-specific modified multidimensional prognostic index (MPI), called Onco-MPI, was calculated for all patients. Onco-MPI score identify three risk score categories (low, moderate and high risk) that predict one-year mortality in older cancer patients. Onco-MPI was calculated according to a validate algorithm as a weighted linear combination of the following CGA domains: age, sex, ADL, IADL, PS, mini-mental state examination, body mass index, CIRS, number of drugs and the presence of caregiver. Cancer sites were also included in the model. Other features analyzed included clinical characteristics, treatment management and outcomes. In our cohort 48% of patients were at advanced Ann Arbor stage (III-IV) with intermediate-high or high risk IPI score in 31%. In 61% of patients we observed extranodal disease, mainly Waldeyer's ring and gastrointestinal tract. First line treatments received included R-CHOP (38%), R-COMP (R-CHOP with non-pegylated liposomial doxorubicin - 23%), R-CVP (14%), R-CEOP (3%), high dose methotrexate (4 patients with primary central nervous system lymphoma), R-VACOP-B (3%), R-Bendamustine in 2 patients and radiotherapy alone was used in 5 patients. Sixty-eight patients (84%) completed the planned cycles of immunochemotherapy. In this group 48,5% required dose reduction for subsequent cycles of treatment because of side effects, in particular hematological toxicities of grade 3-4 or neurological toxicities. In 23 chemotherapy-treated patients initial doses were reduced according to CGA . We observed, after first line therapy, complete response in 63% and partial response in 21%, 8% of patients experienced a disease progression at the end of treatment and 8% died during first line therapy because of lymphoma progression. At time of diagnosis 49% of patients were considered fit at CGA, 16% vulnerable and 35% frail. According to onco-MPI 24 patients (26%) were at low risk of one year mortality, 31 (33%) at medium risk and 38 (41%) at high risk. With a median follow up of 41,1 months the overall survival (OS) of our cohort is 55,9% (95% CI 25,3-56,9). OS correlates with CGA ( 84,4% in fit patients, 31,2 % in vulnerable and 28,1% in unfit, p< 0,001) and Onco-MPI score seems to discriminate our cohort for one-year mortality (95% in low risk, 77% in moderate and 63% in high, p<0,01). OS also correlates with anthracycline administration (67,8% vs 33,3%, p<0,001) as well as the use of consolidation radiotherapy after chemotherapy induction ( 75% vs 49,3%, p <0,01). Our retrospective, single Center experience demonstrates that elderly DLBCL need a multidimensional evaluation at diagnosis in order to identify patients candidate to treatment with curative intent. CGA confirm its role for choosing correct management. Also Onco-MPI can be a useful tool even if more data are needed in lymphoma patients. Disclosures No relevant conflicts of interest to declare.


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