Expert review of hematology
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Brentuximab vedotin (BV) is a potent anti-CD30 antibody drug conjugate (ADC) that has been approved in relapsed or refractory Hodgkin lymphoma (HL) after autologous stem cell transplantation (ASCT) and anaplastic large-cell lymphoma (ALCL). Beyond these consolidated indications, BV has been tested in a number of different settings with promising results, leading for example to the recent approval as a consolidation after ASCT in high-risk HL patients. ⋯ Main emerging areas of clinical investigation of BV include the use as a single-agent or in combination with bendamustine in first-salvage therapy of HL (bridge to ASCT), in the frontline setting in combination with AVD chemotherapy in HL and with CHP in ALCL, in relapsed or refractory cutaneous T-cell lymphomas and finally in diffuse large B-cell lymphomas (DLBCL) expressing CD30. Moreover, many new ADCs are currently under clinical evaluation, as for example the anti-CD79A polatuzumab vedotin in DLBCL. Expert commentary: In few years BV changed the therapeutic scenario of relapsed or refractory HL and ALCL and is rapidly moving toward first-line approval in combination with standard chemotherapy if ongoing randomized trials will demonstrate improved results. Combination strategies with bendamustine in first-salvage HL and with R-CHP in first-line DLBCL appear very promising.
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Richter transformation (RT) represents an aggressive transformation of chronic lymphocytic leukemia (CLL), most commonly into diffuse large B cell lymphoma (DLBCL). It occurs in around 5% of patients with CLL. ⋯ This review will focus on the biology and treatment of RT. We also address the management of RT in the era of targeted therapies. Based on clonal relationship of large cell component to CLL, 2 distinct subtypes could be identified: clonally-related RT which carries a worse outcome, and clonally-unrelated RT where the outcomes are similar to de novo DLBCL. Aberrations of TP53, CDKN2A, MYC, and NOTCH1 are common in RT, many of which are acquired at the time of transformation. PET scan remains the imaging modality of choice for patients with suspected RT. It is important to perform a biopsy rather than fine needle aspiration (FNA) of the suspicious lesions, as FNA can lead to false negative results. Chemoimmunotherapy remains the treatment of choice, though the outcomes remain suboptimal. The median survival is less than 1 year. Novel therapies are needed for patients with RT. Expert commentary: RT remains an unmet medical need; the role of targeted therapies, including immunotherapy needs to be explored.