Daratumumab plus bortezomib and dexamethasone as a bridge to allogeneic transplantation in refractory T-cell lymphoblastic lymphoma

Abstract

Relapsed and refractory (r/r) T-cell lymphoblastic lymphoma (T-LBL) is a highly lethal disease, with no effective treatment options. Daratumumab, an anti-CD38 human IgG1κ monoclonal antibody has been used as single agent in CD38 positive r/r T-LBL. We administered a salvage treatment with daratumumab in combination with bortezomib and dexamethasone regimen followed by allogeneic stem cell transplantation from HLA-haploidentical related donor in a 50 years old patient affected by cortical CD38 positive T-LBL, refractory to 2 prior therapies including first-line cyclophosphamide, vincristine, doxorubicin hydrochloride and dexamethasone (hyper-CVAD) regimen plus autologous stem cell transplantation. After 29 months he is alive and in sustained complete remission, emphasizing the role of daratumumab in combination with bortezomib and dexamethasone as a salvage treatment option in CD38 positive r/r T-LBL patients.

Keywords: Allogeneic hematopoietic stem cell transplantation, Allo-HSCT; Dara-bor-dex, daratumumab-bortezomib-dexamethasone; T-ALL, T-lymphoblastic acute leukemia; T-LBL, T-cell lymphoblastic lymphoma; r/r, relapsed and refractory.

Fig. 1

A (a) Nasopharyngeal Biopsy: The architecture is disrupted by a diffuse proliferation of immature lymphoid cells (H&E; original magnification: 200x), which are positive for CD3 (b), TdT (c), and CD1a (d). The neoplastic cells are negative for CD34 (e). (Original magnification: 400x) (f) Skin Biopsy: The skin exhibits a multifocal nodular lymphoid proliferation within the dermis and subcutaneous adipose tissue (inset, H&E; original magnification: 20x). This proliferation consists of medium-sized atypical lymphoid cells with irregular nuclei, one or two nucleoli, and relatively abundant cytoplasm (H&E; original magnification: 600x). The neoplastic cells are positive for CD3 (g), CD56 (h), TCRgamma (i), and CD38 (k), while negative for TdT (j). (Original magnification: 400x). B a, b) PET/CT scan before treatment with dara-bor-dex: intense uptake in bilateral axillary lymph nodes (arrow), bilateral level II laterocervical, bilateral retro-angulomandibular, bilateral submandibular glands and left supraclavicular lymph nodes. Multiple areas of pathological uptake were present in the skin and soft tissues, notably in the left hand, ipsilateral parieto-occipital region, face, extremities, thorax, and back. Diffuse bone marrow uptake was shown throughout the skeletal system (SUVmax 77) (L, left; R, right) e) CT scan after treatment with dara-bor-dex: a regression of the lymphadenopathies, indicating complete remission (L, left; R, right) c, d) PET/CT scan 3 months after allogeneic HSCT: regression of all pathological uptake areas, indicating complete remission (L, left; R, right)