Complete hematologic response in a patient with multiple pretreated angioimmunoblastic T-cell lymphoma after belinostat therapy followed by allogeneic stem cell transplantation: A case report.

Key Clinical Message: Belinostat therapy followed by hematopoietic stem cell transplantation is a promising salvage strategy for heavily pretreated patients with peripheral T-cell lymphoma. Abstract: Effective treatments for peripheral T-cell lymphoma in the relapsed and refractory (r/r) setting are limited. However, with the development and approval of innovative therapies, effective therapeutic options are becoming available for this patient population. This case report describes the treatment course of a patient with multiple r/r nodal follicular T-helper cell lymphoma of angioimmunoblastic type. Treatment with the histone deacetylase inhibitor belinostat as bridging, enabled allogeneic stem cell transplantation and resulted in a durable complete hematologic response for at least 21 months post-transplantation.

Real-world experience with isatuximab in the treatment of relapsed-refractory multiple myeloma: a case series from the Grand Duchy of Luxembourg.

BACKGROUND & OBJECTIVE: Anti-CD38 targeting has become an important pillar of the treatment for patients with multiple myeloma (MM). This evolution was spearheaded by daratumumab, but more recently isatuximab became the second CD38-directed monoclonal antibody to receive EMA approval for the treatment of patients with relapsed/refractory (RR) MM. In recent years, real-world studies have become increasingly important to confirm and solidify the clinical potential of novel anti-myeloma therapies. METHODS: This article describes the real-world experience with isatuximab-based therapy in a selection of four RRMM patients treated with an isatuximab-based treatment regimen in the Grand Duchy of Luxembourg. RESULTS: Three of the four cases described in this article consist of heavily pretreated patients who were previously exposed to daratumumab-based therapy. Interestingly, the isatuximab-based therapy provided clinical benefit to all three of these patients illustrating that prior exposure to an anti-CD38 mAb does not preclude a response to isatuximab. As such, these findings further support the design of larger prospective studies looking into the impact of prior daratumumab use on the efficacy of isatuximab-based therapy. In addition, two of the cases included in this report displayed renal insufficiency and the experience with isatuximab in these patients further supports the use of this agent in this setting. CONCLUSION: the clinical cases described illustrate the clinical potential of isatuximab-based treatment for RRMM patient in a real-world setting.

Intrinsic Resistance of Chronic Lymphocytic Leukemia Cells to NK Cell-Mediated Lysis Can Be Overcome In Vitro by Pharmacological Inhibition of Cdc42-Induced Actin Cytoskeleton Remodeling.

Natural killer (NK) cells are innate effector lymphocytes with strong antitumor effects against hematologic malignancies such as chronic lymphocytic leukemia (CLL). However, NK cells fail to control CLL progression on the long term. For effective lysis of their targets, NK cells use a specific cell-cell interface, known as the immunological synapse (IS), whose assembly and effector function critically rely on dynamic cytoskeletal changes in NK cells. Here we explored the role of CLL cell actin cytoskeleton during NK cell attack. We found that CLL cells can undergo fast actin cytoskeleton remodeling which is characterized by a NK cell contact-induced accumulation of actin filaments at the IS. Such polarization of the actin cytoskeleton was strongly associated with resistance against NK cell-mediated cytotoxicity and reduced amounts of the cell-death inducing molecule granzyme B in target CLL cells. Selective pharmacological targeting of the key actin regulator Cdc42 abrogated the capacity of CLL cells to reorganize their actin cytoskeleton during NK cell attack, increased levels of transferred granzyme B and restored CLL cell susceptibility to NK cell cytotoxicity. This resistance mechanism was confirmed in primary CLL cells from patients. In addition, pharmacological inhibition of actin dynamics in combination with blocking antibodies increased conjugation frequency and improved CLL cell elimination by NK cells. Together our results highlight the critical role of CLL cell actin cytoskeleton in driving resistance against NK cell cytotoxicity and provide new potential therapeutic point of intervention to target CLL immune escape.