Outcome of Relapsed or Refractory Diffuse Large B-cell Lymphoma with Second-line Chemotherapy Ifosfamide-Carboplatin-Etoposide with or without Rituximab.

Treatment of relapsed or refractory diffuse large B-cell lymphoma is difficult. The de novo diffuse large B-cell lymphoma has better prognosis than the transformed diffuse large B-cell lymphoma. The response of CHOP or a similar regimen has an important role in determining response to salvage therapy, in relapse or refractory diffuse large B-cell lymphoma patients. Patients who are non-responder to initial treatment have a very poor chance of responding to therapy for relapse. This was a small scale observational study and was conducted from January 2017 to December 2020 in National Institute of Cancer Research and Hospital, Bangladesh. A total of 34 patients with relapsed or refractory diffuse large B-cell lymphoma were identified at hematology department in National Institute of Cancer Research and Hospital, 28 of them were treated with ICE chemotherapy and 6 with R-ICE chemotherapy as second line regimen. Overall response rate to 2nd line chemotherapy was 64.8%, with 32.4% (11 patients) complete remission and 32.4% (11 patients) partial remission. Median overall survival to second line regimen was 10 months, corresponding to a 4 year overall survival of 32.4% and a 4 year progression free survival was 17.6%. Patient with stable disease/progressive disease median overall survival was 7 months compared with 15 months for complete remission and 9 months for partial remission (p<0.001). Median overall survival was significantly better in patients with international prognostic index 0-2 compared in those with international prognostic index >2 (p=0.010). However improvement of salvage efficacy is an urgent need with new drugs. Further studies are necessary to determine whether this regimen will improve outcomes of relapsed or refractory diffuse large B-cell lymphoma patients.

SEVERE DISEASE PROGRESSION OF POSTMOLAR GESTATIONAL NEOPLASM IN A VIETNAMESE YOUNG FEMALE PATIENT AFTER TREATMENT REFUSAL: INSIGHTS FROM A CASE REPORT AND LITERATURE REVIEW.

Choriocarcinoma is characterized as the most aggressive malignant alternation of gestational trophoblastic neoplasm; however, this illness is a curable malignancy. Although a rarity, this disease affects a female patient's life and causes a fatal condition. Choriocarcinoma is a life-threatening disease since it is initially insidious and can rapidly lead to masive hemorrhage, even death. Choriocarcinoma should be suspected in childbearing-age women with the high-risk scores according to FIGO. The study aims to report a severe case of widespread metastatic choriocarcinoma to optimize the treatment with multiagent chemotherapy and a multidisciplinary cooperation at our center. A G1P0 20-year-old woman was referred to the hospital for suspicion of metastatic choriocarcinoma after self-stopping chemotherapy because of the COVID-19 pandemic. During hospitalization, the tumor metastasized and presented profuse intraabdominal hemorrhage. The patient underwent immediate surgical intervention to control bleeding, and a definitive diagnosis was accurately established by the histopathological examination. After surgery, the EMA/CO regimen was administered as the first line of treatment, despite the patient being in a coma and requiring a ventilator machine. After 6 cycles of the EMA/CO regimen, her serum ß-hCG level decreased to 8 mUI/mL, however, her ß-hCG concentration was not down to a negative value. Thus, the patient received paclitaxel/cisplatin alternating with paclitaxel/etoposide (TP/TE regimen) for complete remission following 2 cycles. The delays in choriocarcinoma treatment are prognostic factors for worse outcomes, whereas chemotherapy may be considered a suitable treatment even in a patient's coma, thus improving a prognosis substantially.

Mechanism of Drug Resistance to First-Line Chemotherapeutics Mediated by TXNDC17 in Neuroblastomas.

BACKGROUND: The prognosis of high-risk neuroblastomas (NB) that are resistant to first-line induction chemotherapy is relatively poor. This study explored the mechanism of resistance to first-line chemotherapeutics mediated by TXNDC17 and its potential solutions in NB. METHODS: The genetic and clinical data of patients with NB were obtained from the Therapeutically Applicable Research to Generate Effective Treatments dataset. TXNDC17 and BECN1 expressions in NB cells were up- and downregulated by transfection with plasmids and shRNA, respectively. Autophagy-related proteins were detected by western blot. Cell viability was determined using cell proliferation and toxicity experiments. Apoptotic cells were detected using flow cytometry. RESULTS: Overall, 1076 pediatric and adolescent patients with NB were enrolled in this study. The 10-year overall survival (OS) rates and event-free survival (EFS) rates for the patients with a mutation of BECN1 were 37.4 ± 9.1% and 34.5 ± 8.8%, respectively. For patients with a mutation of TXNDC17, the 10-year OS and EFS were 41.4 ± 5.9% and 24.3 ± 5.1%, respectively, which were significantly lower than those in the unaltered group. The overexpression of BECN1 and TXNDC17 reduced NB sensitivity to cisplatin (DDP), etoposide (VP16), and cyclophosphamide (CTX). Autophagy mediated by BECN1 was regulated by TXNDC17, and this process was involved in the resistance to DDP, VP16, and CTX in NB. Suberoylanilide hydroxamic acid (SAHA) can enhance the sensitivity and apoptosis of NB cells to chemotherapeutics by inhibiting TXNDC17, ultimately decreasing autophagy-mediated chemoresistance. CONCLUSIONS: Acquired resistance to first-line chemotherapeutics was associated with autophagy mediated by BECN1 and regulated by TXNDC17, which can be reversed by SAHA.

Phase II study of pegaspargase, etoposide, gemcitabine (PEG) followed by involved-field radiation therapy in early-stage extranodal natural killer/T-cell lymphoma.

OBJECTIVE: The prognosis of extra-nodal NK/T cell lymphoma (ENKTL) is poor, and the optimal therapy remains controversial. This study aims to evaluate the safety and efficacy of a new combined modality therapy. METHODS: Phase-2 study of pegaspargase, etoposide and gemcitabine (PEG) combined with involved field radiation therapy (IFRT) in newly-diagnosed patients with early-stage ENKTL. Patients received 4 course of PEG followed by IFRT. The primary endpoints were complete response (CR), partial response (PR), and objective response rate (ORR) after IFRT. Secondary endpoints included progression-free survival (PFS), overall survival (OS) and adverse events. RESULTS: 34 consecutive patients with Ann Arbor stage I/II were enrolled. 3 patients progressed on PEG, while the remaining 31 received IFRT. The ORR was 88.2% (30/34), included 28 (82.4%) complete and 2 (5.8%) partial responses. With a median follow-up of 56.0 months (Interquartile Range [IQR], 36.0-66.9 months), the estimated 5-year PFS and OS were 87.4% (95% Confidence Interval [CI],69.5%-94.8%) and 97.1% (95%CI, 80.1%-99.6%), respectively. Most adverse events were hematological and easily managed. CONCLUSIONS: PEG followed by IFRT is a safe and effective initial therapy for early-stage ENKTL, demonstrating impressive PFS and OS rates. This promising approach warrants further validation in a randomized controlled trial (Registered at Clinicaltrials.gov NCT02705508).Trial registration: ClinicalTrials.gov identifier: NCT02705508.

Five-year survival in patients with extensive-stage small cell lung cancer treated with atezolizumab in the Phase III IMpower133 study and the Phase III IMbrella A extension study.

OBJECTIVES: IMbrella A is a Phase III extension study that allowed rollover from Roche/Genentech-sponsored atezolizumab trials, including IMpower133, a Phase I/III trial of first-line atezolizumab or placebo plus carboplatin/etoposide in extensive-stage small cell lung cancer. We report outcomes from an exploratory analysis of IMpower133 with extended time-to-event data for patients who rolled over to IMbrella A. MATERIALS AND METHODS: IMpower133 patients could roll over to IMbrella A to receive atezolizumab 1200 mg intravenously every three weeks if they continued to receive atezolizumab at IMpower133 closure or were in survival follow-up after atezolizumab discontinuation. Overall survival and safety were assessed; only serious adverse events and AEs of special interest were collected in IMbrella A. RESULTS: Eighteen of 26 eligible patients rolled over to IMbrella A. At clinical cutoff (March 16, 2023), median follow-up in the atezolizumab plus carboplatin/etoposide arm (IMpower133 and IMbrella A) was 59.4 months. The three-, four-, and five-year overall survival (95 % CI) estimates were 16 % (11 %-21 %), 13 % (8 %-18 %), and 12 % (7 %-17 %), respectively. In IMbrella A, serious adverse events occurred in three patients (16.7 %), and one adverse event of special interest was reported (grade two hypothyroidism). CONCLUSION: This long-term analysis of patients from IMbrella A previously enrolled in IMpower133 provides the first report of five-year overall survival outcomes in patients with extensive-stage small cell lung cancer treated with first-line cancer immunotherapy and chemotherapy. While limited by small patient numbers and lack of long-term data for the IMpower133 control arm, exploratory overall survival analyses in patients treated with atezolizumab plus carboplatin/etoposide compared favorably with historical data with chemotherapy alone. NCT03148418.

Durvalumab with etoposide and carboplatin for patients with extensive-stage small cell lung cancer and interstitial lung disease: A multicenter, open-label prospective trial.

OBJECTIVES: Certain guidelines recommend caution when administering immunotherapy in patients with pre-existing interstitial lung disease (ILD) owing to the high incidence of pneumonitis induced by anti-cancer therapy. A prospective clinical trial assessing the safety of chemoimmunotherapy in patients with small-cell lung cancer (SCLC) and pre-existing ILD is warranted. Therefore, this study evaluated the safety and efficacy of chemoimmunotherapy in patients with extensive-stage (ES)-SCLC and mild idiopathic interstitial pneumonia (IIP). METHODS: In this multicenter prospective trial, patients with ES-SCLC and pre-existing mild chronic fibrosing IIP were recruited. Mild IIP was defined as the exclusion of poor pulmonary function, a definite usual interstitial pneumonia (UIP) pattern, and positivity for autoantibodies in blood tests. The patients received durvalumab, etoposide, and carboplatin every three weeks (induction phase), followed by 1,500 mg durvalumab every four weeks (maintenance phase). The primary endpoint was severe pneumonitis-free rate. RESULTS: Twenty-one patients were included in the analysis. Among them, 13 patients displayed a probable UIP pattern, whereas eight patients exhibited an indeterminate for UIP pattern. Two patients (9.5 %) had pneumonitis of any grade during the induction phase; one had Grade 1 and the other had Grade 5 pneumonitis. No other patient developed pneumonitis during the maintenance phase. The severe pneumonitis-free rate was 95.2 % (95 % confidence interval (CI): 77.3-99.2 %). The median progression-free survival was 5.5 months (95 % CI: 3.6-6.4 months). Median overall survival was 10.7 months (95 % CI: 6.0 months to not reached). CONCLUSIONS: Chemoimmunotherapy is a feasible treatment approach for patients with ES-SCLC and mild IIP.

Importance of immunosuppression in haemophagocytic lymphohistiocytosis caused by miliary tuberculosis.

Haemophagocytic lymphohistiocytosis (HLH) is a syndrome with an abnormal activation of the immune system and is associated with a high mortality even with treatment. We present a case of a woman in her mid-50s who developed HLH triggered by miliary tuberculosis (TB) while receiving a tumour necrosis factor alpha inhibitor.The patient was admitted with a high fever and respiratory pain. Her condition deteriorated despite empirical treatment. Diagnosis of HLH was established based on clinical presentation, H-score and HLH-04 criteria. Concurrently, miliary TB was identified as the trigger. She was treated with anti-tuberculous therapy and HLH-directed treatment with dexamethasone, etoposide and anakinra. Initial improvement was observed, leading to the withholding of HLH-orientated treatment. However, several relapses occurred, necessitating prolonged HLH treatment.A literature review corroborated the importance of combined anti-tuberculous and immunosuppressive therapy for managing HLH. This case underscores the necessity of timely and comprehensive management of HLH-oriented treatment.

Potential therapeutic option for EGFR-mutant small cell lung cancer transformation: a case report and literature review.

Transformation from non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) is rare and is associated with poor prognosis. However, the standard treatment protocols for patients with SCLC transformation remain unknown. Here, we report the case of a patient with advanced EGFR exon 19 deletion (19del) NSCLC who underwent SCLC transformation during targeted therapy. Biopsies and genetic testing were performed to adjust treatment regimens accordingly. The patient responded favorably to a combined treatment regimen comprising etoposide plus cisplatin chemotherapy and adebrelimab plus osimertinib. This case highlights the critical importance of acknowledging tumor heterogeneity in clinical decision-making and identifying potentially effective treatment options for patients with SCLC transformation. Additionally, we reviewed cases of the transformation of NSCLC to SCLC from 2017 to 2023.

Efficacy and safety of standard BEACOPP regimen versus ABVD regimen for treatment of advanced Hodgkin's lymphoma.

INTRODUCTION: The current treatment regimens for Hodgkin's lymphoma (HL) are associated with high incidences of adverse events. PURPOSE: This study aimed to compare the efficacy and safety of doxorubicin + bleomycin + vincristine + dacarbazine (ABVD) and standard bleomycin + etoposide + doxorubicin + cyclophosphamide + vincristine + procarbazine + prednisone (BEACOPP) chemotherapy in the treatment of advanced stage HL. METHODS: This multicenter, randomized, parallel, open, positive control noninferiority trial was conducted from 2016 to 2019 and comprised 93 subjects who were randomized in a 1:1 ratio between the treatment (BEACOPP; n = 44) and control (ABVD; n = 49) groups. RESULTS: The primary efficacy endpoint of this trial was the objective response rate (ORR) after eight cycles of chemotherapy, which was 100.00% (36/36) in the treatment group and 95.74% (45/49) in the control group. The incidence of adverse reactions was 100% in both groups. Significant differences (P < 0.05) in the incidences of grade 3 (39/44 [88.64%] vs. 23/49 [46.94%]) and grade 4 (27/44 [61.36%] vs. 8/49 [16.94%]) adverse events were observed between the treatment and control groups, respectively. However, most of these reactions were manageable, with no serious consequences, and were reversible after discontinuation of the treatment. CONCLUSION: Both regimens had a similar ORR and were associated with a high number of adverse events. The ABVD regimen was better tolerated and safer than the standard BEACOPP regimen. This study indicates that the standard BEACOPP regimen may be considered as a treatment option for patients with advanced HL.

Reinitiating Chemotherapy beyond Progression after Maintenance Immunotherapy in Extensive-Stage Small-Cell Lung Cancer.

Introduction: Small-cell lung cancer (SCLC) is an aggressive form of cancer with a poor prognosis. The two-year survival rate is 8% of all cases. Case presentation: We present the case of a male patient who was 50 years old at the time of diagnosis in May 2022. He was diagnosed with extensive-stage small-cell lung cancer, treated with immunotherapy in combination with chemotherapy (Durvalumab in combination with Etoposide plus Carboplatin) as a first-line treatment, followed by maintenance immunotherapy. In December 2023, a PET-CT scan revealed progressive disease with multiple metastases. Chemotherapy was reinitiated with Etoposide plus Cisplatin in January 2024. After two cycles of chemotherapy, the patient developed post-chemotherapy anemia, for which treatment with Epoetinum alpha was initiated. Chemotherapy was continued for another five cycles, until May 2024, with the maintenance of hemoglobin at a level within 9.9 mg/dL-11 mg/dL. Upon assessment at the end of May 2024, the patient presented an ECOG = 2 performance status, with a moderate general state, moderate-intensity fatigue, no pain, no anxiety or depression and no dyspnea. Discussions, Literature Review and Conclusions: Reinitiating chemotherapy after the failure of maintenance immunotherapy may be an option in patients with SCLC. Epoetinum allows oncological treatment by preventing chemotherapy-induced anemia.

Early Toxicity and Efficacy of Four Different Conditioning Regimens for Autologous Hematopoietic Cell Transplantation in Patients With Lymphoma: Impact of Drug Shortages in a Resource-Constrained Country.

High-dose therapy followed by autologous hematopoietic cell transplant (AHCT) remains a viable consolidation strategy for a subset of patients with relapsed or refractory (R/R) lymphomas. BEAM (carmustine, etoposide, cytarabine, and melphalan) is widely recognized as the predominant conditioning regimen due to its satisfactory efficacy and tolerability. Nevertheless, shortages of carmustine and melphalan have compelled clinicians to explore alternative conditioning regimens. The aim of this study was to compare the toxicity and transplant outcomes following BEAM, CBV (carmustine, etoposide, cyclophosphamide), BuMel (busulfan, melphalan), and BendaEAM (bendamustine, etoposide, cytarabine, melphalan). We retrospectively analyzed data from 213 patients (CBV 65, BuMel 42, BEAM 68, BendaEAM 38) with R/R lymphomas undergoing AHCT between 2014 and 2020. Multivariate models were employed to evaluate toxicity and transplant outcomes based on conditioning type. Among grade III to IV toxicities, oral mucositis was more frequently observed with BuMel (45%) and BendaEAM (24%) compared to BEAM (15%) and CVB (6%, P ≤ .001). Diarrhea was more common with BendaEAM (42%) and less frequent with BuMel (7%, P = .01). Acute kidney injury was only found after BendaEAM (11%). Febrile neutropenia and infectious complications were more frequent following BendaEAM. Frequencies of other treatment-related toxicities did not significantly differ according to conditioning type. BendaEAM (odds ratio [OR] 3.07, P = .014) and BuMel (OR 4.27, P = .002) were independently associated with higher grade III to IV toxicity up to D+100. However, there were no significant differences in relapse/progression, nonrelapse mortality, progression-free survival, or overall survival among the four regimens. BuMel and BendaEAM were associated with a higher rate of grade III to IV toxicity. Carmustine-based regimens appeared to be less toxic and safer; however, there were no significant differences in transplant outcomes. The utilization of alternative preparative regimens due to drug shortages may potentially lead to increased toxicity after AHCT for lymphoma.

Etoposide Therapy of Cytokine Storm Syndromes.

Etoposide has revolutionized the treatment of primary as well as secondary hemophagocytic lymphohistiocytosis (HLH), and it is, together with corticosteroids, the most widely used therapy for HLH. In the early 1980s, long-term survival in primary HLH was <5% but with the etoposide-/dexamethasone-based protocols HLH-94 and HLH-2004, in combination with stem cell transplantation, 5-year survival increased dramatically to around 60% in primary HLH, and based on analyses from the HLH-2004 study, there is likely room for further improvement. Biologically, etoposide administration results in potent selective deletion of activated T cells as well as efficient suppression of inflammatory cytokine production. Moreover, etoposide has also been reported to promote programmed cell death (apoptosis) rather than proinflammatory lytic cell death (pyroptosis), conceivably ameliorating subsequent systemic inflammation, i.e., a treatment very suitable for cytokine storm syndromes (CSS). The combination of etoposide and corticosteroids may also be beneficial in cases of severe or refractory secondary HLH (sHLH) with imminent organ failure, such as infection-associated HLH caused by Epstein-Barr virus (EBV) or malignancy-triggered HLH. In CSS associated with rheumatic diseases (macrophage activation syndrome, MAS or MAS-HLH), etoposide is currently used as second- or third-line therapy. Recent studies suggest that etoposide perhaps should be part of an aggressive therapeutic intervention for patients with severe refractory or relapsing MAS, in particular if there is CNS involvement. Importantly, awareness of sHLH must be further increased since treatment of sHLH is often delayed, thereby missing the window of opportunity for a timely, effective, and potentially life-saving HLH-directed treatment.

Jumonji histone demethylases are therapeutic targets in small cell lung cancer.

Small cell lung cancer (SCLC) is a recalcitrant cancer of neuroendocrine (NE) origin. Changes in therapeutic approaches against SCLC have been lacking over the decades. Here, we use preclinical models to identify a new therapeutic vulnerability in SCLC consisting of the targetable Jumonji lysine demethylase (KDM) family. We show that Jumonji demethylase inhibitors block malignant growth and that etoposide-resistant SCLC cell lines are particularly sensitive to Jumonji inhibition. Mechanistically, small molecule-mediated inhibition of Jumonji KDMs activates endoplasmic reticulum (ER) stress genes, upregulates ER stress signaling, and triggers apoptotic cell death. Furthermore, Jumonji inhibitors decrease protein levels of SCLC NE markers INSM1 and Secretogranin-3 and of driver transcription factors ASCL1 and NEUROD1. Genetic knockdown of KDM4A, a Jumonji demethylase highly expressed in SCLC and a known regulator of ER stress genes, induces ER stress response genes, decreases INSM1, Secretogranin-3, and NEUROD1 and inhibits proliferation of SCLC in vitro and in vivo. Lastly, we demonstrate that two different small molecule Jumonji KDM inhibitors (pan-inhibitor JIB-04 and KDM4 inhibitor SD70) block the growth of SCLC tumor xenografts in vivo. Our study highlights the translational potential of Jumonji KDM inhibitors against SCLC, a clinically feasible approach in light of recently opened clinical trials evaluating this drug class, and establishes KDM4A as a relevant target across SCLC subtypes.

Efficacy and safety of G-CSF prophylaxis in patients with extensive-stage small cell lung cancer receiving chemoimmunotherapy.

OBJECTIVES: We aimed to evaluate the efficacy and safety of granulocyte-colony stimulating factor (G-CSF) prophylaxis during chemoimmunotherapy with carboplatin plus etoposide and atezolizumab in extensive-stage small cell lung cancer (ES-SCLC). METHODS: This retrospective, multicenter study enrolled ES-SCLC patients receiving carboplatin plus etoposide and atezolizumab, categorized into G-CSF and non-G-CSF groups. Demographic and disease-related data were collected. Response rates, progression-free survival (PFS), overall survival (OS), and toxicity were analyzed. RESULTS: Of 119 patients (median age: 63 years), the overall response rate (ORR) and disease control rate (DCR) were 72.3% and 81.5%, respectively. In the G-CSF group, the ORR was 76.4% compared to 60.0% in the non-G-CSF group (p = 0.33), and the DCR was 85.4% versus 70.0%, respectively (p = 0.46). Median PFS was 8.3 months (95% CI, 6.8-9.8) in the G-CSF group and 6.8 months (95% CI, 6.2-7.5) in the non-G-CSF group (p = 0.24). Median OS was 13.8 months (95% CI, 9.6-18.1) for the G-CSF group and 10.6 months (95% CI, 7.9-13.3) for the non-G-CSF group (p = 0.47). Grade 3 ≥ adverse events were similar between groups (49.4% vs. 33.3%, respectively, p = 0.12). CONCLUSION: G-CSF prophylaxis can be safely used in ES-SCLC patients undergoing carboplatin plus etoposide and atezolizumab regimen without significantly altering efficacy or increasing toxicity.

Neuroendocrine carcinoma of the gallbladder: A case report and literature review.

RATIONALE: Neuroendocrine neoplasms (NENs) originating from neuroendocrine cells occur in the thyroid, respiratory, and digestive systems, with Gallbladder Neuroendocrine Carcinoma (GB-NEC) accounting for only 0.5% of all NENs and 2.1% of gallbladder cancers. Due to its rarity, little is known about GB-NEC's clinical presentation and treatment. PATIENT CONCERNS: We report a case of a 52-year-old male presenting with acute upper right abdominal pain, leading to further investigation. DIAGNOSES: Initial diagnostic workup, including abdominal ultrasound and contrast-enhanced CT, suggested gallbladder malignancy. Post-surgical pathology confirmed GB-NEC, with immunohistochemistry supporting the diagnosis. INTERVENTIONS: The patient underwent radical cholecystectomy, followed by etoposide plus cisplatin chemotherapy. After disease progression indicated by CT, the patient received additional cycles of chemotherapy with cisplatin and irinotecan, plus targeted therapy with anlotinib and immunotherapy with paimiplimab. OUTCOMES: The patient showed a partial response to initial treatment. Subsequent liver biopsy confirmed NEC, consistent with small cell carcinoma. With continued treatment, the patient maintains a good survival status. LESSONS: GB-NEC is associated with poor prognosis, emphasizing the importance of early detection and multimodal treatment strategies. Our case underlines the potential benefit of a comprehensive treatment plan, including aggressive surgery and chemotherapy, with further research needed to standardize treatment for this rare condition.

Efficacy and safety of stem cell mobilization with etoposide +cytarabine plus G-CSF in poor mobilizers with relapsed or refractory lymphoma.

Background: Autologous stem cell transplantation (ASCT) is a potentially curative strategy for relapse or refractory(r/r) aggressive lymphoma. However, a proportion of lymphoma patients who are at high risk of mobilization failure fail to mobilize stem cells and cannot proceed to ASCT. The aim of this study is to explore the efficacy and safety of Etoposide combined with Cytarabine (EA) plus G-CSF mobilization in poor mobilizers (PMs) with r/r aggressive lymphoma. Methods: This retrospective study analyzed the outcomes of chemo-mobilization based on EA (Etoposide 0.1 g/m2, qd d1~3; AraC 0.5 g/m2, q12h d1~3) in 98 patients with r/r aggressive lymphoma. Of these, 39 patients met the criteria for predicted PMs as proposed by the Gruppo Italiano Trapianto di Midollo Osseo working group. Results: Of the 39 PMs, 38(97.4%) patents harvested adequate mobilization (≥2×106 CD34+ cells/kg), while 31(79.5%) patients achieved optimal mobilization (≥5×106 CD34+ cells/kg). Overall, the mean number of CD34+ cells/kg collected was 17.99(range: 1.08~83.07) ×106 with an average of 1.4 apheresis sessions, and the number was 15.86(range: 0.37~83.07) ×106 for the first apheresis, respectively. A single apheresis procedure was sufficient to reach the target yield of adequate mobilization in 35(89.7%) PMs, while 76.9% of PMs achieved optimal collection within two apheresis sessions. We observed acceptable hematological toxicity and antibiotic usage exposure in 26 patients with a mean duration of 3.6 days. No grade 4 infection or mobilization-related mortality was recorded. Most patients underwent ASCT and achieved successful hematopoietic recovery with prompt engraftment duration, except for one NK/T-cell lymphoma patient who succumbed to severe septicemia after receiving conditioning chemotherapy. Conclusion: Our findings indicate that EA plus G-CSF is an effective and tolerable CD34+ stem cell mobilization strategy for patients with r/r lymphoma, including those predicted to be PMs. This regimen could be an option for patients with r/r lymphoma, particularly those undergoing mobilization for salvage ASCT therapy.

Clinical and safety outcomes of BeEAM (Bendamustine, Etoposide, Cytarabine, Melphalan) versus CEM (Carboplatin, Etoposide, Melphalan) in lymphoma patients as a conditioning regimen before autologous hematopoietic cell transplantation.

BACKGROUND: Autologous stem cell transplantation (ASCT) is a pivotal treatment for lymphoma patients. The BeEAM regimen (Bendamustine, Etoposide, Cytarabine, Melphalan) traditionally relies on cryopreservation, whereas the CEM regimen (Carboplatin, Etoposide, Melphalan) has been optimized for short-duration administration without the need for cryopreservation. This study rigorously compares the clinical and safety profiles of the BeEAM and CEM regimens. METHODS: A controlled, randomized clinical trial was conducted with 58 lymphoma patients undergoing ASCT at the International Medical Center (IMC) in Cairo, Egypt. Patients were randomly assigned to either the BeEAM (n = 29) or CEM (n = 29) regimen, with an 18-month follow-up period. Clinical and safety outcomes were meticulously compared, focusing on time to engraftment for neutrophils and platelets, side effects, length of hospitalization, transplant-related mortality (TRM), and survival rates. RESULTS: The findings demonstrate a significant advantage for the CEM regimen. Neutrophil recovery was markedly faster in the CEM group, averaging 8.5 days compared to 14.5 days in the BeEAM group (p < 0.0001). Platelet recovery was similarly expedited, with 11 days in the CEM group versus 23 days in the BeEAM group (p < 0.0001). Hospitalization duration was substantially shorter for CEM patients, averaging 18.5 days compared to 30 days for those on BeEAM (p < 0.0001). Furthermore, overall survival (OS) was significantly higher in the CEM group at 96.55% (95% CI: 84.91-99.44%) compared to 79.31% (95% CI: 63.11-89.75%) in the BeEAM group (p = 0.049). Progression-free survival (PFS) was also notably superior in the CEM group, at 86.21% (95% CI: 86.14-86.28%) versus 62.07% (95% CI: 61.94-62.20%) in the BeEAM group (p = 0.036). CONCLUSION: The CEM regimen might demonstrate superiority over the BeEAM regimen, with faster neutrophil and platelet recovery, reduced hospitalization time, and significantly improved overall and progression-free survival rates. Future studies with longer duration and larger sample sizes are warranted. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov under the registration number NCT05813132 ( https://clinicaltrials.gov/ct2/show/NCT05813132 ). (The first submitted registration date: is March 16, 2023).

Nivolumab plus platinum-doublet chemotherapy in treatment-naive patients with advanced grade 3 Neuroendocrine Neoplasms of gastroenteropancreatic or unknown origin: The multicenter phase 2 NICE-NEC trial (GETNE-T1913).

The prognosis of patients with advanced high-grade (G3) digestive neuroendocrine neoplasms (NENs) is rather poor. The addition of immune checkpoint inhibition to platinum-based chemotherapy may improve survival. NICE-NEC (NCT03980925) is a single-arm, phase II trial that recruited chemotherapy-naive, unresectable advanced or metastatic G3 NENs of gastroenteropancreatic (GEP) or unknown origin. Patients received nivolumab 360 mg intravenously (iv) on day 1, carboplatin AUC 5 iv on day 1, and etoposide 100 mg/m2/d iv on days 1-3, every 3 weeks for up to six cycles, followed by nivolumab 480 mg every 4 weeks for up to 24 months, disease progression, death or unacceptable toxicity. The primary endpoint was the 12-month overall survival (OS) rate (H0 50%, H1 72%, ß 80%, α 5%). Secondary endpoints were objective response rate (ORR), duration of response (DoR), progression-free survival (PFS), and safety. From 2019 to 2021, 37 patients were enrolled. The most common primary sites were the pancreas (37.8%), stomach (16.2%) and colon (10.8%). Twenty-five patients (67.6%) were poorly differentiated carcinomas (NECs) and/or had a Ki67 index >55%. The ORR was 56.8%. Median PFS was 5.7 months (95%CI: 5.1-9) and median OS 13.9 months (95%CI: 8.3-Not reached), with a 12-month OS rate of 54.1% (95%CI: 40.2-72.8) that did not meet the primary endpoint. However, 37.6% of patients were long-term survivors (>2 years). The safety profile was consistent with previous reports. There was one treatment-related death. Nivolumab plus platinum-based chemotherapy was associated with prolonged survival in over one-third of chemonaïve patients with G3 GEP-NENs, with a manageable safety profile.

A DPC Database Study on the Safety of Atezolizumab/Carboplatin/Etoposide in Extensive-Disease Small Cell Lung Cancer in Japanese Patients.

INTRODUCTION: Atezolizumab, carboplatin, and etoposide (ACE) therapy is a standard of care for extensive-disease small cell lung cancer (SCLC); however, its safety data are scarce, limiting generalization to the Japanese population. METHODS: This study aimed to compare the safety of ACE versus carboplatin and etoposide (CE) therapies in Japanese patients using the Diagnosis Procedure Combination (DPC) database by comparing the incidence of adverse events (AEs). Retrospective data on clinical background and AEs were extracted from the DPC database. Incidence rates and restricted mean survival times (RMSTs) up to 6 months were analyzed for 19 clinically important AEs. Covariates were adjusted using the inverse probability weighting method. RESULTS: A total of 330,774 patients were identified using the International Statistical Classification of Diseases and Related Health Problems 10th Revision codes, of whom 277 were included in the ACE cohort and 478 in the CE cohort. Among the 19 AEs, the incidence of skin disorder and thyroid dysfunction was significantly higher in the ACE cohort compared with the CE cohort. The adjusted incidence rate ratios were 2.38 (95% confidence interval [CI] 1.04-5.43) for skin disorder and 6.92 (95% CI 2.00-23.89) for thyroid dysfunction. The adjusted RMST differences were - 8.2 days (95% CI - 16.0 to - 0.4 days) for skin disorder and - 8.8 days (95% CI - 15.7 to - 1.9 days) for thyroid dysfunction. CONCLUSIONS: This study provides evidence regarding the safety of ACE combination therapy in Japanese clinical practice using the DPC database, with results comparable to those reported in pivotal clinical trials. TRIAL REGISTRATION: UMIN Clinical Trials Registry ID UMIN000041508.

Effectiveness of R-CHOP versus R-CHOEP for treatment of young patients with high-risk diffuse large B-cell lymphoma: A Danish observational population-based study.

PURPOSE: Etoposide to standard R-CHOP is used for high-risk diffuse large B-cell lymphoma (DLBCL) in some countries. Due to the lack of randomized trials, a real-world data study using matching methods was used to test the potential effectiveness of R-CHOEP over R-CHOP. PATIENTS AND METHODS: This study included patients from the Danish Lymphoma Register diagnosed between 2006 and 2020 at the age of 18-60 years with de novo DLBCL and age-adjusted IPI ≥2. R-CHOEP treated patients were matched 1:1 without replacement to R-CHOP treated patients using a hybrid exact and genetic matching technique. Primary endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS: In total, 396 patients were included; 213 received R-CHOEP and 183 received R-CHOP. Unadjusted 5-year PFS and OS for R-CHOEP were 69% (95% Confidence intervals [CI]; 63%-76%) and 79% (CI;73%-85%) versus 62% (CI;55%-70%) and 76% (CI;69%-82%) for R-CHOP (log-rank test, PFS p = .25 and OS p = .31). A total of 127 patients treated with R-CHOEP were matched to 127 patients treated with R-CHOP. Matching-adjusted 5-year PFS and OS were 65% (CI; 57%-74%) and 79% (CI; 72%-84%) for R-CHOEP versus 63% (CI; 55%-73%) and 79% (CI;72%-87%) for R-CHOP (log-rank test, PFS p = .90 and OS p = .63). CONCLUSION: The present study did not confirm superiority of R-CHOEP over R-CHOP for young patients with high-risk DLBCL.