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Summary: A chemotherapy‐based mobilization regimen in patients who mobilize poorly, based on etoposide, cytarabine and pegfilgrastim (EAP), has recently been introduced. The aim of this prospective study was to investigate the efficacy and safety of the EAP regimen in patients with poorly mobilizing multiple myeloma (MM) or lymphoma. This single‐arm clinical trial was performed at eight public hospitals in China and was registered as a clinical trial (NCT05510089). The inclusion criteria were; (1) diagnosis of MM or lymphoma, (2) defined as a 'poor mobilizer' and (3) aged 18–75 years. The EAP regimen consisted of etoposide 75 mg/m2/day on days 1–2, cytarabine 300 mg/m2 every 12 h on days 1–2 and pegfilgrastim 6 mg on day 6. The primary endpoint of the study was the ratio of patients achieving adequate mobilization (≥2.0 × 106 CD34+ cells/kg). From 1 September 2022 to 15 August 2023, a total of 58 patients were enrolled, 53 (91.4%) achieved adequate mobilization, while 41 (70.7%) achieved optimal mobilization with a median number of cumulative collected CD34+ cells was 9.2 (range 2.1–92.7) × 106/kg and the median number of apheresis per patient of 1.2. The median time from administration of the EAP regimen to the first apheresis was 12 days. Approximately 8.6% of patients required plerixa for rescue, which was successful. Twelve (20.7%) of the 58 patients suffered grade 2–3 infections, while 25 (43.1%) required platelet transfusions. The duration of neutrophil and platelet engraftment was 11 days. In conclusion, these results suggest that the EAP mobilization regimen might be a promising option for poorly mobilizing patients with MM or lymphoma. [ABSTRACT FROM AUTHOR]

Summary: Gilteritinib, a potent FMS‐like tyrosine kinase 3 (FLT3) inhibitor, was approved for relapsed/refractory (R/R) FLT3‐mutated acute myeloid leukaemia (AML) patients but still showed limited efficacy. Here, we retrospectively analysed the efficacy and safety of different gilteritinib‐based combination therapies (gilteritinib plus hypomethylating agent and venetoclax, G + HMA + VEN; gilteritinib plus HMA, G + HMA; gilteritinib plus venetoclax, G + VEN) in 33 R/R FLT3‐mutated AML patients. The composite complete response (CRc) and modified CRc (mCRc) rates were 66.7% (12/18) and 88.9% (16/18) in patients received G + HMA + VEN, which was higher compared with that in G + HMA (CRc: 18.2%, 2/11; mCRc: 45.5%, 5/11) or G + VEN (CRc: 50.0%, 2/4; mCRc: 50.0%, 2/4). The median overall survival (OS) for G + HMA + VEN, G + HMA and G + VEN treatment was not reached, 160.0 days and 231.0 days. The median duration of remission (DOR) for G + HMA + VEN, G + HMA and G + VEN treatment was not reached, 82.0 days and 77.0 days. Four patients in the G + HMA + VEN group received alloHSCT after remission exhibited prolonged median DOR. The most common grade 3/4 adverse events were cytopenia, febrile neutropenia and pulmonary infection; there were no differences among the three groups. In conclusion, our data demonstrated promising response of G + HMA + VEN combination therapy in R/R FLT3‐mutated AML, and it may be considered an effective therapy bridge to transplantation. [ABSTRACT FROM AUTHOR]

Background: Early T cell precursor acute lymphoblastic leukemia (ETP-ALL) is a distinct subtype of T-ALL with a poor prognosis. To find a cure, we examined the synergistic effect of homoharringtonine (HHT) in combination with the BCL-2 inhibitor venetoclax (VEN) in ETP-ALL., Methods: Using in vitro cellular assays and ETP-ALL xenograft models, we first investigated the synergistic activity of HHT and VEN in ETP-ALL. Next, to explore the underlying mechanism, we employed single-cell RNA sequencing of primary ETP-ALL cells treated with HHT or VEN alone or in combination and validated the results with western blot assays. Based on the promising preclinical results and given that both drugs have been approved for clinical use, we then assessed this combination in clinical practice., Findings: Our results showed that HHT synergizes strongly with VEN both in vitro and in vivo in ETP-ALL. Mechanistic studies demonstrated that the HHT/VEN combination concurrently downregulated key anti-apoptotic proteins, i.e., MCL1, leading to enhanced apoptosis. Importantly, the clinical results were very promising. Six patients with ETP-ALL with either refractory/relapsed (R/R) or newly diagnosed disease were treated with an HHT/VEN-based regimen. All patients achieved complete remission (CR) after only one cycle of treatment., Conclusions: Our findings demonstrate that a combination of HHT/VEN is effective on ETP-ALL and represents the "backbone" of a promising and safe regimen for newly diagnosed and R/R patients with ETP-ALL., Funding: This work was funded by the National Cancer Institute, Gehr Family Foundation, George Hoag Family Foundation, National Natural Science Foundation of China, and Key Research and Development Program of Zhejiang Province of China., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To describe the side effects of bortezomib in treatment of multiple myeloma (MM), especially the incidence of peripheral neuropathy (PN)., Methods: Information of 107 patients with MM who were treated with bortezomib in the First Affiliated Hospital of Zhejiang University from 2009 to 2014, were collected and analyzed retrospectively, to analyze the occurrence of adverse events during the treatment, especially the incidences of PN in each cycle and in different patients., Results: A total of 40 (37%) patients suffered from PN, among which 13 patients were grade 3 PN and no patients reported grade 4 PN. Other common treatment-related side effects were thrombocytopenia, gastrointestinal reactions, fatigue, lung infection, herpes zoster in turn. In 44 MM patients treated strictly with bortezomib 1.3 mg/m(2) (days 1, 4, 8, 11) of each 3-week cycle, 20(45%) patients suffered from PN, of which 6 (14%) patients got grade 3 PN. In other 63 patients who received bortezomib less than 1.3 mg/m(2), 20 (32%) patients got PN and 7(11%) patients were grade 3 PN. There was no significant difference in the incidence of PN between the two groups of MM patients mentioned above (P=0.149), as well as the incidence of grade 3 PN (P=0.694). Univariate and multivariate analyse revealed that gender, age, a history of hypertensive disease, diabetes or hepatitis B virus infection, baseline PN symptoms and a history of neurotoxicity drug therapy were all not risk factors for PN (all P>0.05)., Conclusions: The reduction of bortezomib do not decrease the incidence of PN in bortezomib treatment of MM. Age, a history of diabetes and baseline PN symptoms are not risk factors for PN in bortezomib treatment of MM.