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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]

Autologous stem cell transplantation (ASCT) is a salvage therapy for relapsed or refractory diffuse large B-cell lymphoma (DLBCL). We have developed a novel conditioning regimen called CEAC (oral semustine 250 mg/m2 d-6, etoposide 300 mg/m2 d-5 ~ d-2, cytarabine 500 mg/m2 d-5 ~ d-2, and cyclophosphamide 1200 mg/m2 d-5 ~ d-2) In lymphoma patients in China. Here, we conducted a study to compare the conventional BEAM regimen with the CEAC regimen in 110 DLBCL patients. Propensity-score matching was performed in a 1:4 ratio (22 patients received BEAM and 88 received CEAC). Our results showed no significant difference in the overall response rate (95% vs 97%, P = 1.000) and complete response rate (66% vs 73%, P = 0.580) between the two cohorts. The 5-year progression-free survival (PFS), 5-year overall survival (OS), and 5-year cumulative incidence of relapse (CIR) for all patients were 72% (95% CI 62%–82%), 92% (95% CI 86%–97%), and 29% (95% CI 17%–38%), respectively. There was no significant difference in the 5-year PFS (80% vs 70%, P = 0.637), 5-year OS (95% vs 91%, P = 0.496), and 5-year CIR (20% vs 30%, P = 0.733) between cohorts. In terms of safety, the CEAC cohort had a lower incidence rate of grade 1–2 gastrointestinal hemorrhage (P = 0.023) and severe nausea (P = 0.007) compared with the BEAM cohort. In conclusion, the CEAC regimen seems to be a suitable alternative to the BEAM regimen for ASCT in DLBCL patients. [ABSTRACT FROM AUTHOR]

Objectives: Our research aimed to evaluate the effectiveness of first‐line immune checkpoint inhibitors (ICIs) with etoposide and platinum (EP) for extensive‐stage small cell lung cancer (ES‐SCLC) and identify prognostic factors, as real‐world outcomes and the inconsistency of PD‐1 and PD‐L1 inhibitors are uncertain. Methods: We selected ES‐SCLC patients in three centers and conducted a propensity score‐matched analysis. The Kaplan–Meier method and Cox proportional hazards regression were conducted to compare the survival outcomes. We also performed univariate and multivariate Cox regression analyses to investigate predictors. Results: Among 236 patients included, 83 pairs of cases were matched. The EP plus ICIs cohort had a longer median overall survival (OS) (17.3 months) than the EP cohort (13.4 months) (hazard ratio [HR], 0.61 [0.45, 0.83]; p = 0.001). The median progression‐free survival (PFS) was also longer in the EP plus ICIs cohort (8.3 months) than in the EP cohort (5.9 months) (HR, 0.44 [0.32, 0.60]; p < 0.001). The EP plus ICIs group had a higher objective response rate (ORR) (EP: 62.3%, EP + ICIs: 84.3%, p < 0.001). Multivariate analysis presented that liver metastases (HR, 2.08; p = 0.018) and lymphocyte–monocyte ratio (LMR) (HR, 0.54; p = 0.049) were independent prognostic factors for OS, and performance status (PS) (HR, 2.11; p = 0.015), liver metastases (HR, 2.64; p = 0.002), and neutrophil‐lymphocyte ratio (NLR) (HR, 0.45; p = 0.028) were for PFS in patients with chemo‐immunotherapy. Conclusion: Our real‐world data demonstrated that ICIs with chemotherapy as the first‐line setting for ES‐SCLC are effective and safe. PS, liver metastases, and inflammatory markers could serve as valuable risk factors. [ABSTRACT FROM AUTHOR]

Aim: The diagnosis and treatment of hemophagocytic lymphohistiocytosis (HLH) in pregnancy is challenging due to its rarity. We aim to analyze and summarize the clinical characteristics of HLH in pregnancy, and to discuss effective diagnostic and treatment options. Methods: Thirteen patients with HLH during pregnancy who were diagnosed and treated at the Peking Union Medical College Hospital of the Chinese Academy of Medical Sciences from January 2000 to December 2019 were studied retrospectively. We collected data on treatment regimens and on maternal and pregnancy outcomes. Results: All patients had a singleton pregnancy, with a median age of 28 years (range, 22–33 years) and a median gestational age of 23 weeks (7–36 weeks). Twelve patients received corticosteroids, and four patients (with/without intravenous immunoglobulin) showed a curative effect. Two patients who were treated with dexamethasone and etoposide after termination of pregnancy achieved complete remission. Two patients attained remission after termination of pregnancy. Four pregnant women died, and the mortality rate was 30.8% (4/13). Fetal or neonatal death up to 1 week after delivery occurred in eight (61.5%) pregnancies. Conclusions: Early diagnosis and treatment are important for maternal survival, and corticosteroids are the first choice for most patients with HLH during pregnancy. For patients who do not respond to corticosteroids, etoposide and termination of pregnancy may be life‐saving. [ABSTRACT FROM AUTHOR]

Background: Extensive-disease small-cell lung cancer (ED-SCLC) is characterized by rapid progression and relapse, despite high initial response rates to chemotherapy. The primary objective of this trial was to demonstrate the non-inferiority of amrubicin and cisplatin (AP) combination therapy compared with the standard first-line regimen of etoposide and cisplatin (EP) for previously untreated ED-SCLC in a Chinese population. When non-inferiority was verified, the objective was switched from non-inferiority to superiority.Methods: From June 2008 to July 2010, 300 patients were enrolled and randomly assigned at a 1:1 ratio to AP and EP groups. AP-treated patients received cisplatin (60 mg/m(2), day 1) and amrubicin (40 mg/m(2), days 1-3) once every 21 days. EP-treated patients received cisplatin (80 mg/m(2), day 1) and etoposide (100 mg/m(2), days 1-3) once every 21 days. Treatment was continued for four to six cycles, except in cases of progressive disease or toxicity, and patient refusal.Results: Median overall survival (OS) for AP vs. EP treatment was 11.8 vs. 10.3 months (p = 0.08), respectively, demonstrating non-inferiority of AP to EP (AP group: 95% confidence interval for hazard ratio 0.63-1.03 months). Median progression-free survival and overall response rates for AP vs. EP groups were 6.8 vs. 5.7 months (p = 0.35) and 69.8% vs. 57.3%, respectively. Drug-related adverse events in both groups were similar, with neutropenia being the most frequent (AP 54.4%; EP 44.0%). Leukopenia, pyrexia, and fatigue were more prevalent in the AP group, but all were clinically reversible and manageable.Conclusions: AP therapy demonstrated non-inferiority to EP therapy, prolonging OS for 1.5 months, but this difference was not statistically significant; thus we propose AP as a promising treatment option for ED-SCLC in China.Trial Registration: This trial was registered on 10 April 2008 (ClinicalTrials.gov NCT00660504). [ABSTRACT FROM AUTHOR]

Background This study evaluated the efficacy and safety of irinotecan/cisplatin ( IP) and etoposide/cisplatin ( EP) in extensive-stage small cell lung cancer ( ES-SCLC) and the distribution of uridine diphosphate glucuronosyltransferase ( UGT1A1). The relationship between UGT1A1 genotypes and patient outcomes was also assessed. Method Patients with untreated ES-SCLC were randomly assigned to receive either IP or EP, and blood specimens were collected to test the genotypes of UGT1A1*28 and UGT1A1*6. The association of efficacy and toxicity of an IP regimen with UGT1A1 genotype was analyzed. Results Of the 62 patients enrolled from three institutions, 30 patients were in the IP and 32 patients were in the EP arms, respectively. Disease control rates with IP and EP were 83.3% and 71.9%, respectively ( P = 0.043). Median progression-free survival for IP and EP were both six months. Median overall survival for IP and EP were 18.1 and 15.8 months respectively, without significant difference. Grade 3-4 thrombocytopenia was more common with EP (18.8% vs. 6.7%; P = 0.035), while the incidence of diarrhea was higher with IP (70% vs. 15.6%; P = 0.008). The incidence of grade 1-4 late-onset diarrhea of wild-type, heterozygous, and homozygous UGT1A1*28 were 65.0%, 85.7%, and 66.7%, respectively ( P = 0.037). UGT1A1*28 polymorphisms, Eastern Cooperative Oncology Group performance status, and chemotherapy cycles were essential factors affecting grade 1-4 late-onset diarrhea in logistic regression analysis. Conclusions The efficacy of the IP regimen was similar to the EP regimen for untreated ES-SCLC. UGT1A1 polymorphisms were associated with late-onset diarrhea; however, there was no influence on efficacy. [ABSTRACT FROM AUTHOR]

Background Maintenance therapy for extensive stage small cell lung cancer ( ES-SCLC) is still under debate. Many new agents fail during the maintenance course. As an active agent for SCLC, oral etoposide is worth being re-evaluated. Methods This phase II study was performed to evaluate the toxicity/efficacy of the maintenance of patients with oral etoposide with ES-SCLC responding (complete remission [ CR] + partial remission [ PR]) to the induction of four cycles of etoposide plus cisplatin ( EP) chemotherapy. Maintenance therapy with oral etoposide (50 mg/m2, day 1-14, repeated every 21 days until disease progression or unacceptable toxicity occurs) was administered. The primary endpoints were grade 3 and 4 toxicities and progression free survival ( PFS). Results Fifty-four patients with ES-SCLC received standard EP regimens as induction therapy; 31 responding patients were administered oral etoposide as the maintenance treatment. The most common hematological and non-hematological toxicity of the maintenance course was neutropenia and fatigue, respectively. Median PFS was nine months (95% confidence interval ( CI): 8.33∼9.67 months), median overall survival ( OS) was 14 months (95% CI: 11.58∼16.42 months). Significantly better PFS and OS were seen in patients responding to the induction EP chemotherapy. Conclusions Oral etoposide maintenance is safe and effective for patients with ES-SCLC who responded to the induction of EP chemotherapy. Significant survival benefit was revealed in patients completely responding to an EP regimen. Further randomized control study is warranted. [ABSTRACT FROM AUTHOR]

For osteosarcoma that progresses following first-line chemotherapy, prognosis remains poor although anti-angiogenesis tyrosine kinase inhibitors (TKIs) have been verified to prolong progression-free survival. Apatinib has led to positive responses in the treatment of refractory osteosarcoma. However, it demonstrates only short-lived activity, and the disease control rate of musculoskeletal lesions is worse compared with that of pulmonary lesions. This treatment failure has been partly overcome by the addition of ifosfamide and etoposide (IE). The present study retrospectively compared the activity of apatinib + IE in relapsed or refractory osteosarcoma in two sarcoma centres in China. The included patients had received a combination of apatinib 500 mg (orally) daily and the IE regimen (n=33) between June 3 2017 and July 17 2020. The tumour burden was considerable in these patients: 16/33 (48.5%) Patients had lung and musculoskeletal lesions, and 31/33 (93.9%) patients had progressed to two lines of therapies at baseline. With a median follow-up duration of 28.4 [interquartile range (IQR), 16.1–38.3] months, 21/33 (63.6%) patients had objective responses, and the median event-free survival was 11.4 (IQR, 6.7–18.4) months. The median overall survival time was 19.8 (IQR, 13.1–30.6) months. At the last follow-up, 16/33 patients had tumour downstaging, and all lesions had been completely resected. For osteosarcoma with multiple sites of metastasis, apatinib + IE demonstrated clinically meaningful antitumor activity and delayed disease progression in patients with recurrent or refractory osteosarcoma after failure of chemotherapy. This combination with manageable toxicity deserves further investigation in prospective trials. [ABSTRACT FROM AUTHOR]