Diffuse large B-cell lymphoma in Southeast Asian cohort: expression patterns of B-cell receptor (BCR) repertoire and its linkage with molecular subtypes and response to R-CHOP therapy
JOURNAL OF CLINICAL PATHOLOGY
Authors: Masir, Noraidah; Akhter, Ariz; Roshan, Tariq M.; Florence, Chandramaya Sabrina; Abdul-Rahman, Faridah; Tumian, Nor Rafeah; Kean-Chang, Phang; Elyamany, Ghaleb; Shabani-Rad, Meer-Taher; Mansoor, Adnan
Abstract
Aims Heightened B-cell receptor (BCR) activity in diffuse large B-cell lymphoma (DLBCL) is well established, and a subset of patients with relapsed DLBCL can benefit from BCR-targeted therapies. Universal outreach of such emerging therapies mandates forming a global landscape of BCR molecular signalling in DLBCL, including Southeast Asia. Methods 79 patients with DLBCL (nodal, 59% and extranodal, 41%) treated with rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) therapy were selected. Expression levels of BCR and linked signalling pathway molecules were inter-related with Lymph2Cx-based cell of origin (COO) types and overall survival (OS). Results Activated B-cell (ABC) type DLBCL constituted 49% (39/79) compared with germinal centre B-cell (GCB) type DLBCL (29/79; 37%) and revealed poor prognosis (p=0.013). In ABC-DLBCL, high BTK expression exerted poor response to R-CHOP, while OS in ABC-DLBCL with low BTK expression was similar to GCB-DLBCL subtype (p=0.004). High LYN expression coupled with a poor OS for ABC-DLBCL as well as GCB-DLBCL subtypes (p=0.001). Furthermore, high coexpression of BTK/LYN (BTKhigh/LYNhigh) showed poor OS (p=0.019), which linked with upregulation of several genes associated with BCR repertoire and nuclear factor-kappa B pathway (p<0.01). In multivariate analysis, high BTK and LYN expression retained prognostic significance against established clinical predictive factors such as age, International Prognostic Index and COO (p<0.05). Conclusions Our data provide a clear association between high BCR activity in DLBCL and response to therapy in a distinct population. Molecular data provided here will pave the pathway for the provision of promising novel-targeted therapies to patients with DLBCL in Southeast Asia.
Ibrutinib as a salvage therapy after allogeneic HCT for chronic lymphocytic leukemia
BONE MARROW TRANSPLANTATION
Authors: Michallet, Mauricette; Dreger, Peter; Sobh, Mohamad; Koster, Linda; Hoek, Jennifer; Boumendil, Ariane; Scheid, Christof; Fox, Christopher P.; Wulf, Gerald; Krueger, William; van Gelder, Michel; Corradini, Paolo; Russo, Domenico; Passweg, Jakob; Schoemans, Helene; Bethge, Wolfgang; Schaap, Nicolaas; Cornelissen, Jan; Browne, Paul; Durakovic, Nadira; Muller, Lutz; Montoto, Silvia; Kroger, Nicolaus; Schetelig, Johannes
Abstract
The purpose of our study is to provide information on safety and efficacy of ibrutinib as salvage treatment after allo-HSCT for CLL. A total of 56 patients were included, 36 (64%) males; median age at transplantation was 48 years (range: 35-64) and the median number of treatment lines prior to transplantation was 3 (1-10). The median time between allo-HSCT and Ibrutinib was 30 months (range: 1-140). Overall, 40 (71%) patients responded to Ibrutinib; 23 (41%) PR, and 17 (30%) CR. At time of ibrutinib initiation, ten patients had active chronic GVHD that resolved under Ibrutinib, whilst a single patient developed limited de novo chronic GVHD on Ibrutinib. Fourteen patients discontinued ibrutinib, four because of toxicity and ten because of disease progression. Overall, 14 patients progressed (median PFS = 24 months) among them 10 died. Two-year OS and PFS probabilities were 72% (95% CI: 52-84) and 50% (95% CI: 32-66), respectively. Patients with late relapse after allo-HSCT (>= 24 months) had a better PFS after ibrutinib. Our study shows that ibrutinib can be safely administered for CLL relapse after allo-HSCT, with comparable efficacy to non-transplanted patients with high-risk disease.
COA
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