Perspectives on chemotherapy for the management of double-hit lymphoma.

INTRODUCTION: Double-hit (DHL) and triple-hit lymphomas (THL) have long been among the most clinically aggressive molecular subtypes of diffuse large B-cell lymphomas. In the 2016 revised WHO classification, they represent a new entity called high-grade B-cell lymphoma with rearrangements of MYC and BCL2 and/or BCL6. Unlike most B-cell lymphomas, they have poor response to standard R-CHOP therapy, tend to quickly develop resistance to cytotoxic chemotherapies, and are associated with higher central nervous system (CNS) infiltration. This can lead to increased risk of relapse and worse prognosis. DHL/THL represent a subset of lymphomas with unmet medical need. AREA COVERED: The authors present the available data for the current treatment regimens including intensive chemotherapy regimens, hematopoietic stem-cell transplantation (HSCT), and CNS prophylaxis. They also discuss treatment for relapsed disease including targeted therapies. EXPERT OPINION: There is currently no accepted standard of care for DHL/THL. For frontline therapy, we recommend enrollment in a well-designed clinical trial if possible, otherwise DA-EPOCH-R with CNS prophylaxis is a commonly used first-line therapy. The authors recommend close surveillance for patients achieving complete response, but for those who fail to achieve a complete response, then clinical trials, more aggressive salvage chemotherapy regimens, or cellular therapies are usually considered.

Marginal Zone Lymphoma: State-of-the-Art Treatment.

OPINION STATEMENT: Despite being the second most common indolent non-Hodgkin's lymphoma (iNHL), marginal zone lymphoma (MZL) remains largely understudied, and given its underlying disease heterogeneity, it is challenging to define a single treatment approach for these patients. For localized disease, local therapy is recommended such as triple therapy for H. pylori in gastric extranodal MZL, splenectomy for splenic MZL, and radiotherapy for nodal MZL. For disseminated disease with low tumor burden, a watch and wait or single-agent rituximab can be used. However, for symptomatic disease, a similar approach to follicular lymphoma (FL) can be used with chemoimmunotherapy approaches such as bendamustine and rituximab. High FDG uptake is not common in MZL and is not diagnostic by itself of transformation to high-grade lymphoma but informs the choice of the site to be biopsied. Transformation into a large B cell lymphoma is treated with R-CHOP-like regimens. Patients with relapsing disease after at least one CD20-based therapy have several recently approved chemotherapy-free options including B cell receptor inhibitors such ibrutinib (approved specifically in MZL) and immunomodulatory agents such as lenalidomide and rituximab (FDA approved in MZL and FL). Phosphoinositide 3-kinase (PI3K) inhibitors have shown excellent activity in iNHL, specifically in MZL, with breakthrough designation status for copanlisib and umbralisib, allowing off label use of this class of agents in clinical practice. With the availability of prospective clinical trials using chemo-free approaches, specifically those targeting abnormal signaling pathways activated in MZL tumors and its microenvironment, treating physicians are encouraged to enroll patients on these clinical trials in order to better understand the underlying biology, mechanisms of response, and resistance to current therapies and help design future rationale combination strategies.

Hematopoietic stem cell mobilization following PD-1 blockade: Cytokine release syndrome after transplantation managed with ascorbic acid.

Checkpoint inhibitor therapy is effective in the treatment of relapsed classical Hodgkin's Lymphoma. Here, we report a patient with relapsed Hodgkin's Lymphoma who received nivolumab prior to autologous stem cell mobilization. She went on to develop cytokine storm shortly following transplantation, with marked T-cell proliferation coincident with myeloid engraftment. Non-cardiogenic pulmonary edema and alveolar hemorrhage developed despite corticosteroid therapy. There was rapid and complete resolution of these complications with parenteral ascorbic acid infusion. Our case illustrates the risk of cytokine release syndrome following infusion of stem cells mobilized after checkpoint inhibitor therapy and the role of ascorbic acid in its management.