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Summary: Patients with FLT3‐mutated acute myeloid leukaemia (AML) that relapse or are refractory (R/R) to intensive induction have poor outcomes. Gilteritinib has recently become standard‐of‐care for patients with R/R FLT3‐mutated AML. We investigated whether adding venetoclax to gilteritinib (gilt‐ven) improves outcomes as compared with gilteritinib monotherapy. We included patients treated with gilteritinib (n = 19) and gilt‐ven (n = 17) for R/R AML after intensive chemotherapy. Gilteritinib and gilt‐ven groups did not differ in terms of mCRc rates (53% and 65%, p = 0.51) and realization of allogeneic haematopoietic stem‐cell transplantation (HSCT, 47% and 35%, p = 0.5). Overall survival (OS) was comparable between groups, although a trend towards better OS was seen with gilt‐ven (12‐month OS 58.8% [95% CI 39.5%–87.6%]) versus gilteritinib (42.1% [95% CI 24.9%–71.3%] for gilteritinib). Early salvage with gilt‐ven versus any other gilteritinib‐based approach was associated with the best outcome (p = 0.031). Combination therapy was associated with increased haematological toxicity. In summary, gilt‐ven did not improve remissions or HSCT‐realization rates in patients with R/R FLT3‐mutated AML as compared with gilteritinib and was associated with increased haematological toxicity. Although OS did not differ, a trend towards better survival was suggested with gilt‐ven and a survival benefit was shown for gilt‐ven approach when sequenced early for salvage. [ABSTRACT FROM AUTHOR]

Introduction: Extracorporeal photopheresis (ECP) is considered an effective treatment for patients with chronic graft vs host disease (cGVHD) and demonstrates efficacy in ameliorating GVHD. The mechanism by which ECP acts against cGVHD is not fully understood. Preliminary observations have hinted at the potential involvement of neutrophil extracellular traps (NETs) formation in the pathogenesis of cGVHD. We aimed to assess the influence of ECP on the formation of NETs in patients with cGVHD as a potential mechanism in this setting. Methods: Patients treated with ECP for cGVHD at the Rabin Medical Center were included in this study. Blood samples were obtained at three different time points: before starting an ECP cycle, at the end of the first day of treatment, and 24 h following the initiation of the ECP treatment cycle. Neutrophils were harvested from all blood samples. NET formation was assessed by measurement of NET‐bound specific neutrophil elastase activity and by immunofluorescence staining. Results: Six patients (two females and four males) with cGVHD were included in the study. We observed a significant increase in NET formation among all six patients following ECP. Net‐bound specific neutrophil elastase activity was elevated from a median value of 2.23 mU/mL (interquartile range [IQR] 2.06‐2.47 mU/mL) at baseline to a median value of 13.06 mU/mL (IQR 10.27‐15.97 mU/mL) immediately after the treatment and to a peak median value of 14.73 mU/mL (IQR 9.6‐22.38 mU/mL) 24 h following the initiation of the ECP cycle. A qualitative assessment of NET formation using immunofluorescence staining has demonstrated markedly increased expression of citrullinated histone H3, a marker of NET formation, following ECP treatment. Conclusions: Our preliminary data indicate that ECP induces NET formation among patients with cGVHD. The contribution of increased NET formation to the therapeutic effect of cGVHD should be further investigated. [ABSTRACT FROM AUTHOR]

Simple Summary: Light-chain amyloidosis is a rare disease, and treatment for relapsed light-chain amyloidosis patients is an unmet need. Venetoclax is an oral medication that has proven great efficacy in many hematological cancers, including multiple myeloma. Venetoclax is considered a promising agent for the treatment of relapsed light-chain amyloidosis. We aimed to report the outcomes of therapy in 26 relapsed light-chain amyloidosis patients treated with venetoclax. We found a very high response rate (88%), and most responses were deep and prolonged. Treatment was effective even when doses were reduced. Venetoclax treatment was safe, and one patient died due to infection. These promising results require confirmation in a randomized trial. Therapeutic options in relapsed refractory (R/R) light-chain (AL) amyloidosis patients are limited. Given the encouraging results in t(11;14) multiple myeloma and the high prevalence of t(11;14) in AL amyloidosis, venetoclax is an attractive treatment option in this setting. We report here the results of a multi-center retrospective study on 26 R/R AL amyloidosis patients treated off-label with venetoclax. The median lines of therapy prior to venetoclax was 3.5 (range 1–7), and 88% of our cohort had t (11;14). Twenty-two patients (85%) were previously treated with daratumumab. The overall hematologic response rate was 88%, 35% achieved a CR, and 35% achieved VGPR. The median event-free survival was 25 months (m) (95% CI 9.7 m-not reached), and the median overall survival was 33 m (95% CI 25.9–39.2 m). Most of the patients in this cohort are in ongoing deep responses and continuing venetoclax therapy. The treatment was relatively safe. One patient died due to infection, and there were two grade 3 infections in our cohort. Tumor lysis syndrome (TLS) was not seen in any patient. Dose reductions were frequent but did not affect the efficacy. These promising results require confirmation in a randomized controlled trial. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the role of additional chemotherapy before autologous hematopoietic cell transplantation (HCT) in patients with relapse/refractory diffuse large B‐cell lymphoma (DLBCL) who achieve partial remission following first salvage therapy. Methods: We conducted a multicenter retrospective study of all adult patients with DLBCL who underwent HCT between 2008 and 2020 and achieved partial response (PR) after the first salvage and were either referred directly to HCT (n = 47) or received additional salvage therapy before HCT (n = 22). Results: Post‐HCT CR rate and progression‐free survival were comparable between the two groups (66% vs. 68%, p =.86 and median not reached vs. 10.2 months [95% confidence interval, CI 7.1–12.3], p =.27, respectively). Median overall survival (OS) and estimated 3‐year OS favored patients who were directly referred to HCT (105.8 [95% CI 63–148] months vs. 14.5 [95% CI 0–44] months, p =.035, and 65% [95% CI 51%–75%] vs. 40% [95% CI 21%–53%], p =.035, respectively). In Cox regression model, while International Prognostic Index and primary refractory versus relapse disease did not impact OS, allocation to a second salvage regimen and older age were both associated with inferior survival (hazard ratio [HR] = 2.57 95% CI 1.1–5.8, p =.023 and HR = 1.04 95% CI 0.99–1.2, p =.064, respectively). Conclusions: Referring patients with chemotherapy‐sensitive disease in PR directly to HCT is associated with better OS compared to those receiving additional lines of treatment. [ABSTRACT FROM AUTHOR]

This article discusses a case of fatal invasive pulmonary and cerebral aspergillosis caused by a triazole-resistant strain of Aspergillus fumigatus with multiple CYP51A mutations. Triazoles, such as voriconazole, are the primary treatment for invasive pulmonary aspergillosis, but triazole resistance in A. fumigatus has been increasing. The most common resistance mechanism is alterations in the CYP51A coding sequence or promoter. The patient in this case had autosomal recessive chronic granulomatous disease and had been treated with various antibiotics and voriconazole prophylaxis. Despite treatment with antifungal drugs, the patient's condition worsened and they eventually died. The isolated A. fumigatus strain had a CYP51A mutation with a 46 bp tandem repeat in the promoter and five amino acid substitutions in the coding sequence. This mutation has not been previously identified in clinical A. fumigatus isolates in Israel. It is unclear whether the mutated spores were acquired from the environment or due to prolonged voriconazole exposure. [Extracted from the article]