Clinical impact of [18F]FDG-PET/CT in ARI0002h treatment, a CAR-T against BCMA for relapsed/refractory multiple myeloma [Retrospective study].

Highlights:

●       Progression free-survival and overall-survival are shorter in patients with extramedullary plasmacytomas evaluated by [¹⁸F]fluorodeoxyglucose (FDG)–positron emission tomography (PET)/computed tomography (CT) at infusion time.

●       Survival is predicted by a metabolic tumor volume of ≥25 cm³ at baseline and [¹⁸F] FDG-PET/CT response (Bologna criteria) on day 100.

●       These results highlight the importance of extramedullary disease evaluation by [¹⁸F]FDG-PET/CT before and after chimeric antigen receptor (CAR) T-cell infusion.

This study included 63 patients with relapsed/refractory multiple myeloma treated either in the CARTBCMA-HCB-01 clinical trial (ARI0002h; academic B-cell maturation antigen [BCMA]–targeted CAR T-cell therapy) or in compassionate use.

Fixed-Duration Acalabrutinib Combinations in Untreated Chronic Lymphocytic Leukemia [Phase 3 clinical trial].  

Highlights:

●       In this interim analysis of the AMPLIFY trial of fit patients with previously untreated chronic lymphocytic leukemia (CLL), fixed-duration acalabrutinib–venetoclax (with or without obinutuzumab) significantly prolonged progression-free survival (PFS) as compared with chemoimmunotherapy.

●       The safety profile of fixed-duration acalabrutinib–venetoclax in this trial aligned with that in previous studies of acalabrutinib.

This study included 867 patients with CLL who did not have a 17p deletion or TP53 mutation. They were randomised in a 1:1:1 ratio so that 291 patients were assigned to receive acalabrutinib–venetoclax, 286 acalabrutinib–venetoclax–obinutuzumab, and 290 chemoimmunotherapy. The median age of the patients was 61 years (range, 26 to 86), 64.5% were men, and 58.6% had unmutated IGHV (immunoglobulin heavy chain). The primary end point was the estimated 36-month PFS (acalabrutinib–venetoclax vs. chemoimmunotherapy) in the intention-to-treat population, assessed by blinded independent critical review.

CD4+ T-Cell Lymphoma Harboring a Chimeric Antigen Receptor Integration in TP53 [Case report].

Malignant T-cell transformation after chimeric antigen receptor (CAR) T-cell therapy has been described, but the contribution of CAR integration to oncogenesis is not clear. This is a case report of a T-cell lymphoma harboring a lentiviral integration in a known tumor suppressor TP53, which developed in a patient with multiple myeloma (MM) after B-cell maturation antigen (BCMA) CAR T-cell therapy (cilta-cel). A 72-year-old woman with relapsed, triple-class–refractory IgA kappa MM and a high-risk cytogenetic profile had received four lines of myeloma directed therapy (including two autologous hematopoietic stem-cell transplantations) before treatment with fludarabine–cyclophosphamide lymphodepleting chemotherapy followed by cilta-cel. Approximately 2 months after infusion, the patient reported new and persistent nausea, vomiting, anorexia, and intractable watery, non-bloody diarrhea and was ultimately hospitalized. She underwent upper endoscopic and flexible sigmoidoscopic evaluations. A definitive diagnosis was made.

Hemophagocytic Lymphohistiocytosis [Review].

Key points: 

●       Hemophagocytic lymphohistiocytosis (HLH) syndrome is often classified as a primary (genetic [typically caused by defective cytotoxic lymphocytes]) form or a secondary (acquired, non-Mendelian) form (See Table 1 in original article). The most common triggers for secondary HLH are infections, cancers, and autoimmune diseases; HLH with an autoimmune trigger is also referred to as macrophage activation syndrome (MAS-HLH). HLH associated with cancer has two forms: “malignancy-triggered HLH” (HLH identified at diagnosis or relapse of cancer) and “HLH during chemotherapy.”

●       HLH is a life-threatening syndrome of overwhelming inflammation (hyperinflammation) that causes multiorgan failure and death, making prompt and appropriate treatment imperative.

●       HLH should be considered, and ferritin levels should be checked in patients with a sepsis-like critical illness that does not respond to adequate empirical treatment.

●       The HLH-94 and HLH-2004 protocols (based on etoposide, dexamethasone, and cyclosporine) remain standard care for primary HLH.  A complete remission before hematopoietic stem cell transplantation (HSCT) is beneficial but not mandatory for survival after HSCT.

●       In patients with secondary HLH, treatment is adapted to the underlying condition and the severity of the HLH.

●       In patients with moderate secondary HLH, glucocorticoids with or without intravenous immunoglobulin may be sufficient, and addition of anakinra can be considered. Cyclosporine is not often used in adults except in those with MAS-HLH.

●       In patients with severe, nonresponsive, or progressive secondary HLH, particularly those with CNS involvement, imminent organ failure, or both, prompt addition of weekly treatment with etoposide is often recommended at an age-adjusted dose.

●       Chronic, active EBV infection is a progressive, fatal disease characterized by organ failure, hypercytokinemia, HLH, and overt lymphomatous or leukemic changes, for which allogeneic HSCT is recommended.

●       A consensus review has suggested a two-step therapeutic approach to organ damage from malignancy-associated HLH. First, target the cytokine storm and T-cell proliferation with etoposide at a moderate dose, glucocorticoids, and possibly intravenous immunoglobulin, and then, when organ function has improved sufficiently, target the neoplastic disease.