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研究グループは、白血病マウスモデルを使用した実験において、ロペグインターフェロンが生体内でがん細胞に作用するメカニズムを明らかにしました。ロペグインターフェロンが血液がんの治療で有望な結果が出ているとの報告が近年増加しています。しかし、そのメカニズムは明らかではありませんでした。本研究では、ロペグインターフェロンが腫瘍細胞に対して、直接的な細胞傷害作用をもたらしているのか、もしくは細胞そのものではなく間接的に免疫調整作用をもたらしているのかを検証しました。その結果、優れた抗腫瘍免疫作用を確認し、中でもT細胞の活性化が重要な役割を担っていることが分かりました。これは、幅広いがん種での応用の可能性も示唆しています。加えて、白血病細胞が体内から消失したマウスに再び白血病細胞株を注入しても再発しなかったことから、免疫記憶が獲得され、再発率の低下につながる可能性があると考えられます。, Although ropeginterferon alfa-2b has recently been clinically applied to myeloproliferative neoplasms with promising results, its antitumor mechanism has not been thoroughly investigated. Using a leukemia model developed in immunocompetent mice, we evaluated the direct cytotoxic effects and indirect effects induced by ropeginterferon alfa-2b in tumor cells. ...

For successful chimeric antigen receptor T (CAR-T) cell therapy, CAR-T cells must be manufactured without failure caused by suboptimal expansion. In order to determine risk factors for CAR-T cell manufacturing failure, we performed a nationwide cohort study in Japan and analysed patients with diffuse large B-cell lymphoma (DLBCL) who underwent tisagenlecleucel production. We compared clinical factors between 30 cases that failed (7.4%) with those that succeeded (n = 378). Among the failures, the proportion of patients previously treated with bendamustine (43.3% vs. 14.8%; p, CAR-T細胞製造を成功させるためのレシピ --アフェレーシス前の下ごしらえでの工夫--. 京都大学プレスリリース. 2023-04-27.

Lay abstract This case report describes a 72-year-old man with non-small-cell lung cancer who received four cycles of pembrolizumab-containing chemotherapy. He developed multiple immune-related adverse events (irAEs), which are significant side effects of immune checkpoint inhibitors (ICIs). Despite the discontinuation of pembrolizumab due to multiple irAEs, he developed immune-related hepatitis and neutropenia at 92 days and 118 days, respectively, after the final pembrolizumab dose. He received supportive care and immunosuppressive therapy and recovered from neutropenia. Recently, delayed development of irAEs was reported even in patients that discontinued ICIs; this is referred to as a delayed immune-related event (DIRE). This case developed strikingly delayed immune-related neutropenia as a DIRE. Clinicians should pay close attention to neutropenia as a possible life-threatening DIRE after ICI treatment.

OBJECTIVES The short-term efficacy of virtual-assisted lung mapping (VAL-MAP), a preoperative bronchoscopic multi-spot lung-marking technique, has been confirmed in 2 prospective multicentre studies. The objectives of this study were to analyse the local recurrence and survival of patients enrolled in these studies, long-term. METHODS Of the 663 patients enrolled in the 2 studies, 559 patients’ follow-up data were collected. After excluding those who did not undergo VAL-MAP, whose resection was not for curative intent, who underwent concurrent resection without VAL-MAP, or who eventually underwent lobectomy instead of sublobar resection (i.e. wedge resection or segmentectomy), 422 patients were further analysed. RESULTS Among 264 patients with primary lung cancer, the 5-year local recurrence-free rate was 98.4%, and the 5-year overall survival (OS) rate was 94.5%. Limited to stage IA2 or less (≤2 cm in diameter; n = 238, 90.1%), the 5-year local recurrence-free and OS rates were 98.7% and 94.8%, respectively. Among 102 patients with metastatic lung tumours, the 5-year local recurrence-free rate was 93.8% and the 5-year OS rate was 81.8%. Limited to the most common (colorectal) cancer (n = 53), the 5-year local recurrence-free and OS rates were 94.9% and 82.3%, respectively. CONCLUSIONS VAL-MAP, which is beneficial in localizing small barely palpable pulmonary lesions and determining the appropriate resection lines, was associated with reasonable long-term outcomes. Subj collection 152, 1542

We described and compared the mating behavior and morphology of the reproductive system in chromodorid nudibranchs, then, examined how extensively the unique usage of the penis (autotomy and sperm removal) evolved among Chromodorids. In addition to Ardeadoris egretta, all of examined five species in Glossodoris autotomized their penises at the last stage of copulation. An interspecific difference was seen in penis autotomy in Noumea and Goniobranchus. A spiral structure was recognized in the vas deferens of autotomized species. This structure is supposed to be undifferentiated “next penises” stored in the vas deferens, which ensure successive copulation in autotomized species. Though the basic mechanism of penis replenishment was consistent, the reason to autotomize their penises may not be the same. Goniobranchus reticulatus is reported to remove sperm already stored in the mating partner’s sperm storage organ(s) with backward-pointing spines on the surface of its penis. Contrary to G. reticulatus, all of ten species that autotomized their penises in the present study did not have thorny but smooth penises. When they autotomized their penises, the tip of the penises still remained in the vagina of the partners. This suggests that autotomized penises in these nudibranchs function as a kind of copulatory plugs.

BACKGROUND: This feasibility study aimed to detect respiratory waveforms from thoracic movements and evaluate if postoperative complications could be predicted using a carbon nanotube sensor. METHODS: Fifty patients who underwent lung resection for lung tumors were enrolled. The lung monitoring system of the carbon nanotube sensor was placed on bilateral chest walls across the 6(th)–9(th) ribs to measure chest wall motion. We examined the respiratory waveform in relation to surgical findings, postoperative course, and complications using Hilbert transform and Fast Fourier Transform (FFT). RESULTS: Of 50 patients (37 males, 13 females), 22 were included in the normal lung function group and 28 were included in the low lung function group. The respiratory rate and waveform indicated a regular pattern in the normal lung function group and the respiratory rate could be detected. Conversely, irregular respiratory pattern was detected in 70% of patients in the low lung function group. There was no significant different overall envelope peak value between operated side and non-operated side (0.195±0.05 and 0.18±0.06). In contrast, there was significantly high peak value in the presence of postoperative complications (P

Due to the COVID-19 pandemic, the 84thAnnual Meeting of the Japanese Circulation Society (JCS) was held in a web-based format for the first time in its history as "The Week for JCS 2020" from Monday, July 27 to Sunday, August 2, 2020. All sessions, including general abstracts, were streamed live or on-demand. The main theme of the meeting was "Change Practice!" and the aim was to organize the latest findings in the field of cardiovascular medicine and discuss how to change practice. The total number of registered attendees was over 16,800, far exceeding our expectations, and many of the sessions were viewed by far more people than at conventional face-to-face scientific meetings. At this conference, the power of online information dissemination was fully demonstrated, and the evolution of online academic meetings will be a direction that cannot be reversed in the future. The meeting was completed with great success, and we express our heartfelt gratitude to all affiliates for their enormous amount of work, cooperation, and support.

Background: There are several prognosis prediction models about allogeneic hematopoietic cell transplantation (allo-HCT) such as the hematopoietic cell transplantation specific comorbidity index (HCT-CI) and the refined disease risk index (R-DRI). Although HCT-CI and R-DRI are valuable and commonly used, further improvement of these models is desirable because the prognostic predictive abilities for post-allo-HCT survival remain suboptimal. Both brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP), are released from the ventricular and atrial walls, in response to the walls stretch into the blood. Plasma BNP and NT-proBNP levels are well-known biomarkers of the predictors of death in patients with cancer and heart disease. However, it is unclear whether these biomarkers are useful predictors for prognosis after allo-HCT. The main aim of our study was to evaluate the potential role of plasma BNP and NT-proBNP levels in predicting the mortality in allo-HCT patients. Methods: We retrospectively registered consecutive patients who underwent allo-HCT from January 2011 to December 2018. Plasma BNP and NT-proBNP examinations and echocardiography within 1 month from the start of conditioning regimen were performed in all transplant candidates as pretransplant work-up in our institution. Cox regression models were used to estimate the hazard ratios (HRs) with 95% confidence intervals (95% CI) in the univariate and multivariate analyses. Relapse/progression (Rel/Prog) and non-relapse mortality (NRM) were considered competing events. The Fine-Gray proportional hazard regression model was used for the univariate and multivariate analyses with competing risks. A p value < 0.050 was considered statistically significant. We estimated the two models using c-statistics on the basis of time to event, using the total follow-up period to compare the predictive accuracy of R-DRI or HCT-CI with BNP or NT-proBNP added models. Standard errors (SEs) for the c-statistics were estimated by applying a bootstrap procedure using 1000 bootstrap samples to confirm the reproducibility. The SEs for the difference in c-statistics between these two models were compared with the above bootstrap samples and used to compute a z-score and a p value for the difference, similar to that in several previous studies. Results: We enrolled 174 consecutive patients. The median age was 49 (range: 16-68) years. During the follow-up period, 64 patients died (36.8%). Both plasma BNP and NT-proBNP levels showed a significant association with OS and NRM, but not Rel/Prog in the univariate analysis. Next, we conducted multivariable analysis to evaluate the independence of plasma BNP and NT-proBNP levels by adjusting for not only those variables that were reported as prognostic factors in the previous research for OS, but also diastolic dysfunction that can be associated with plasma BNP and NT-proBNP levels. We constructed each two and three multivariable model, including either BNP or NT-proBNP to assess the effects of these biomarkers on OS and NRM according to the one-in-ten rule 6 to avoid overfitting (Table 1). The adjusted models for OS showed that higher plasma BNP and NT-proBNP levels were significantly associated with poorer outcomes. Moreover, the adjusted models for NRM showed that a higher plasma BNP level was significantly associated with the outcome. We also evaluated the prognostic significance of BNP, NT-proBNP, HCT-CI, or echocardiographic parameters, including ejection fraction (EF) and diastolic dysfunction, by adding to R-DRI via computation of the c-statistic. BNP or NT-proBNP showed significantly higher c-statistic estimates for OS as compared with R-DRI alone (c-statistic estimate 0.741, 0.759, and 0.674, respectively), but not EF or diastolic dysfunction (Table 2). Both plasma BNP and NT-proBNP levels had higher HRs for OS [HR per standard deviation (SD) 2.57 (95% CI: 1.75-3.76), p < 0.001, and HR per SD 1.95 (95% CI: 1.39-2.73), p < 0.001] and NRM [HR per SD 2.10 (95% CI: 1.11-3.97), p < 0.024, and HR per SD 2.57 (95% CI: 1.92-3.44), p < 0.001] even in the normal heart function group. Conclusion: Plasma BNP and NT-proBNP levels are easy to perform and cost-effective; thus, these could be useful independent biomarkers for predicting allo-HCT prognosis than echocardiography. They enable clinical decision regarding allo-HCT. Disclosures Okamura: NIPPON SHINYAKU CO.,LTD: Honoraria. Nakane:Pfizer Japan Inc.: Research Funding; Janssen Pharmaceutical K.K.: Research Funding; Bayer Yakuhin, Ltd: Research Funding; Novartis: Honoraria, Research Funding; DAIICHI SANKYO COMPANY, LIMITED: Honoraria; Mundipharma K.K: Honoraria. Nanno:Otsuka Pharmaceutical Co., Ltd: Honoraria. Nishimoto:Bayer Yakuhin, Ltd:: Research Funding; Janssen Pharmaceutical K.K.:: Research Funding. Nakamae:Shire Japan KK: Honoraria; Celgene Corporation: Honoraria; DAIICHI SANKYO COMPANY, LIMITED: Honoraria; Takeda Pharmaceutical Company Limited: Honoraria; Chugai Pharmaceutical Co., Ltd: Honoraria; Japan Blood Products Organization: Honoraria; NIPPON SHINYAKU CO.,LTD: Honoraria; Novartis: Honoraria; Pfizer Japan Inc.: Honoraria; Bristol-Myers Squibb: Honoraria; Kyowa-Hakko Kirin Co.,Ltd: Honoraria; Amgen Astellas BioPharma K.K: Honoraria; Astellas Pharma Inc.: Honoraria; Otsuka Pharmaceutical Co., Ltd: Honoraria; ONO PHARMACEUTICAL CO., LTD.: Honoraria. Nakashima:Amgen Astellas BioPharma K.K: Honoraria; Novartis: Honoraria, Research Funding; Eisai Co., Ltd: Honoraria, Research Funding; Amgen Inc: Honoraria; Kyowa-Hakko Kirin Co.,Ltd: Honoraria; Kyowa Kirin Co., Ltd: Honoraria; JCR Pharmaceuticals Co., Ltd: Honoraria; Pfizer Japan Inc: Honoraria; Astellas Pharma Inc: Research Funding; SymBio Pharmaceuticals Limited: Research Funding; Celgene Corporation: Research Funding; AbbVie GK: Research Funding; M S D K. K: Research Funding. Koh:Takeda Pharmaceutical Company Limited: Honoraria, Research Funding; Sumitomo Dainippon Pharma Co., Ltd: Honoraria; M S D K. K: Honoraria; NIHON PHARMACEUTICAL CO., LTD: Honoraria; Chugai Pharmaceutical Co., Ltd: Research Funding; Asahi Kasei Corporation: Research Funding; Amgen Astellas BioPharma K.K: Research Funding; IQVIA Services Japan K.K.: Research Funding; Takeda Science Foundation: Research Funding. Hino:Kyowa-Kirin: Honoraria, Research Funding; Chugai: Honoraria, Research Funding; Otsuka: Honoraria, Research Funding; Astellas: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Taiho: Research Funding; Teijin: Research Funding; MSD: Honoraria, Research Funding; Sumitomo Dainippon: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria; Daiichisankyo: Honoraria, Research Funding; Eisai: Research Funding; Jansenn: Honoraria; Celgene: Honoraria; Mochida: Honoraria; Ono: Honoraria; Sanofi: Honoraria; Japan Blood Products Organization: Research Funding; Nippon Shinyaku: Honoraria; Nihon Pharmaceutical: Research Funding; Mundi Pharma: Honoraria; Alexion: Honoraria. Nakamae:Pfizer Japan Inc: Honoraria, Research Funding; Astellas Pharma Inc: Honoraria, Research Funding; Otsuka Pharmaceutical Co., Ltd: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Amgen Astellas BioPharma K.K: Honoraria; ONO PHARMACEUTICAL CO., LTD: Honoraria; Kyowa-Hakko Kirin Co.,Ltd: Honoraria; Shire Japan KK: Honoraria; Celgene Corporation: Honoraria; DAIICHI SANKYO COMPANY, LIMITED: Honoraria; Takeda Pharmaceutical Company Limited: Honoraria; Chugai Pharmaceutical Co., Ltd: Honoraria; Japan Blood Products Organization: Honoraria; NIPPON SHINYAKU CO.,LTD: Honoraria; Novartis: Honoraria; PPD-SNBL K.K: Research Funding.

Tyrosine kinase inhibitor (TKI) can help to increase the survival time in chronic myeloid leukemia (CML) patients; however, the risk of secondary malignancies due to TKIs is a growing concern. Only few reports showed clinical course of patients who developed lymphoma during TKI therapies. Herein, we report a case of high‐grade B‐cell lymphoma diagnosed in the course of CML treatment with bosutinib. The 75‐year‐old male patient had been diagnosed with CML 25 years ago. After receiving TKIs (imatinib, nilotinib, and bosutinib), he achieved a major molecular response. Over 3 years after starting bosutinib, he was diagnosed with a high‐grade B‐cell lymphoma. A total of six courses of DA‐EPOCH‐R therapy brought complete remission of the lymphoma. Moreover, BCR‐ABL1 transcript copies remained undetectable by RT‐PCR, 8 months after stopping bosutinib. The risk of secondary malignancy due to TKI has been controversial. It is reported that TKI induces irreversible chromosomal abnormalities or chromosome aberrations and inhibits the proliferation or function of T cells, B cells, and NK cells. These mechanisms of TKI may contribute to the development of secondary malignancy. There remains no consensus on the management of secondary lymphoma during TKI therapies. At present, the only alternative is to observe patients receiving TKI treatment cautiously and to treat secondary lymphoma in the same manner as de novo lymphoma., There remains no consensus on the management of secondary lymphoma during TKI therapies. The only alternative is to observe patients receiving TKI treatment cautiously and to treat secondary lymphoma in the same manner as de novo lymphoma.

The phase 3 ICARIA-MM trial showed that the addition of isatuximab improved the progression-free survival compared with pomalidomide/dexamethasone. However, the safety and efficacy of isatuximab for end-stage renal failure remains unclear. A 67-year-old man who started hemodialysis 5 years ago for diabetic nephropathy was diagnosed with International Staging System stage III multiple myeloma (MM) of IgD-λ type 3 years ago. After receiving a total of 7 treatment regimens, his free light chain (FLC) λ level increased from 419 to 2,070 mg/L, indicating progressive disease. Twelve days after starting isatuximab plus pomalidomide (3 mg daily) and dexamethasone (IsaPd), his FLC λ level rapidly decreased to 412 mg/L. The patient has now completed 7 courses of IsaPd with no adverse events, including infusion reactions and neutropenia. Isatuximab requires a lower dilution volume than daratumumab and can be safely and effectively administered to hemodialysis-dependent MM patients.

Idiopathic pure red cell aplasia (PRCA) and secondary PRCA associated with thymoma and large granular lymphocyte leukemia are generally considered to be immune-mediated. The PRCA2004/2006 study showed that poor responses to immunosuppression and anemia relapse were associated with death. PRCA may represent the prodrome to MDS. Thus, clonal hematopoiesis may be responsible for treatment failure. We investigated gene mutations in myeloid neoplasm-associated genes in acquired PRCA. We identified 21 mutations affecting amino acid sequences in 11 of the 38 adult PRCA patients (28.9%) using stringent filtering of the error-prone sequences and SNPs. Four PRCA patients showed 7 driver mutations in TET2, DNMT3A and KDM6A, and 2 PRCA patients carried multiple mutations in TET2. Five PRCA patients had mutations with high VAFs exceeding 0.3. These results suggest that clonal hematopoiesis by stem/progenitor cells might be related to the pathophysiology of chronic PRCA in certain adult patients.

ObjectiveHeart failure following allogeneic haematopoietic stem cell transplantation (allo-HSCT) is a serious complication that requires early detection; however, the clinical implications of early-onset cancer therapy-related cardiac dysfunction (CTRCD) following allo-HSCT remain unclear. We investigated the determinants and prognostic impact of early-onset CTRCD in allo-HSCT recipients.MethodsThe records of 136 patients with haematological malignancies who underwent allo-HSCT at our institute were retrospectively reviewed. Early-onset CTRCD was defined as a decrease in left ventricular ejection fraction (LVEF) of ≥10% and an LVEF of ≤53% within 100 days after HSCT.ResultsEarly-onset CTRCD was diagnosed in 23 out of 136 included patients (17%), and the median duration from HSCT to CTRCD diagnosis was 24 (9–35) days. Patients were followed up for 347 (132–1268) days. In multivariate logistic regression analysis, cumulative doxorubicin dosage (each 10 mg/m2) and severity of acute graft-versus-host disease (GVHD/grade) were independent indicators of early-onset CTRCD (OR (95% CI) 1.04 (1.00 to 1.07); p=0.032; OR (95% CI) 1.87 (1.19 to 2.95), p=0.004, respectively). The overall and primary disease death rates were significantly higher in allo-HSCT recipients with early-onset CTRCD than in those without early-onset CTRCD (HR (95% CI) 1.98 (1.11 to 3.52), p=0.016; HR (95% CI) 2.96 (1.40 to 6.29), p=0.005, respectively), independent of primary disease type, remission status and transplantation type.ConclusionsSevere acute GVHD and higher cumulative anthracycline are two significant determinants of early-onset CTRCD. Early-onset CTRCD following allo-HSCT regulates survival in patients with haematological malignancies.

Bone marrow necrosis (BMN) is a rare but important complication of hematological malignancies. We report the case of a 52-year-old male patient with a recurrence of acute lymphoblastic leukemia (ALL) accompanied by BMN. After re-induction therapy, bone marrow aspiration (BMA) and biopsy from the iliac bone showed necrotic cells and eosinophilic debris, respectively. Magnetic resonance imaging (MRI) showed heterogeneous signals in the bilateral iliac bone, possibly reflecting various stages of BMN. BMA from the sternum eventually revealed the recurrence of ALL after a few weeks. Comprehensive assessments, including MRI and repeated bone marrow tests, are required when evaluating the underlying hematological malignancies of patients with BMN.

Tuberculous peritonitis is difficult to diagnose due to the disadvantages of ascitic culture and peritoneal biopsy. Although previous reports suggested that very high serum soluble interleukin-2 receptor (sIL-2R) levels may reflect the clinical activity of tuberculosis, little is known about the diagnostic utility of serum sIL-2R for tuberculous peritonitis. We describe a case of tuberculous peritonitis with chronic myelogenous leukemia. The abnormally high serum sIL-2R value and negative findings for other possible causes including lymphoma suggested tuberculous peritonitis and we administered anti-tuberculosis treatment before definitive diagnosis. Abnormally high serum sIL-2R levels may contribute to earlier diagnosis of tuberculous peritonitis, along with ruling out other potential differential diagnoses.

A 53-year-old man presented with uncontrolled bleeding caused by acquired platelet dysfunction accompanied by calreticulin-mutated primary myelofibrosis. Based on the detection of abnormal platelets, including large gray platelets, under light microscopy and the loss of the second wave of aggregation observed by light transmission aggregometry, the patient was diagnosed with platelet dysfunction accompanied by myeloproliferative neoplasms (MPNs). In addition, the absence of platelet α-granules was confirmed by electron microscopy. Therefore, this condition may be termed "acquired gray platelet syndrome." Acquired platelet dysfunction must be ruled out when abnormal platelets are observed in patients with MPNs.

HLA-haploidentical allogeneic hematopoietic cell transplantation (allo-HCT) using post-transplantation cyclophosphamide (PT/Cy-haplo) is becoming the standard of care for patients without an HLA-matched related or unrelated donor. PT/Cy-haplo can give more patients the opportunity to undergo allo-HCT, because most patients have multiple available HLA-haploidentical related donor candidates. The optimal donor selection algorithm in the PT/Cy-haplo setting has not yet been established, however. To contribute to the establishment of a donor selection formula based on disease status and killer-cell immunoglobulin-like receptor (KIR) genotype, we retrospectively analyzed 91 patients who underwent PT/Cy-haplo at our institution. In both patients and donors, HLA allele genotyping was performed for HLA-A, -B, -C, and -DRB1, and 16 KIR genes were genotyped. Patients in complete remission (CR) who underwent PT/Cy-haplo from a KIR2DS1-positive donor had a significantly lower cumulative incidence of relapse (CIR) than those who underwent PT/Cy-haplo from a KIR2DS1-negative donor (1-year CIR: 0% versus 32.6%, P = .037; 2-year CIR: 9.2% versus 42%, P = .037). Moreover, PT/Cy-haplo from a KIR2DS1-positive donor was significantly associated with improved overall survival (OS) (1-year OS: 91.7% versus 58.7%, P = .010; 2-year OS: 83% versus 34%, P = .010). In contrast, in non-CR individuals, PT/Cy-haplo from KIR2DS1-positive donors did not significantly improve CIR or OS (1-year CIR: 56.5% versus 64.7%, P = .973; 2-year CIR: not reached versus 64.7%, Pnot evaluable; 1-year OS: 25.4% versus 20.6%, P = .418; 2-year OS: 5.1% versus 20.6%, P = .418). In addition, lower infused CD34+ cell dose, female-to-male transplantation, and acute myelogenous leukemia were significantly associated with increased risk of relapse and mortality. This study demonstrates that graft-versus-leukemia/tumor effects were exerted through donor KIR2DS1 at PT/Cy-haplo when patients have low tumor burdens. It would be worth examining the inclusion of donor KIR genotyping and disease status assessment in establishing optimal donor selection criteria for PT/Cy-haplo.

Adult patients with relapsed/refractory (R/R) B‐precursor acute lymphoblastic leukemia (ALL) have a poor prognosis. Blinatumomab is a bispecific T‐cell engager (BiTE) immuno‐oncology therapy with dual specificity for CD19 and CD3 that redirects patients’ CD3‐positive cytotoxic T cells to lyse malignant and normal B cells. We conducted an open‐label, phase 1b/2 study to determine the safety, pharmacokinetics, efficacy and recommended dose of blinatumomab in Japanese adults with R/R B‐precursor ALL. Patients received 9 μg/day blinatumomab during week 1 and 28 μg/day during weeks 2‐4, with a 2‐week treatment‐free interval (6‐week cycle); patients received 28 μg/day blinatumomab in subsequent cycles. Primary endpoints were the incidence of dose‐limiting toxicities (DLT) in phase 1b and complete remission (CR)/CR with partial hematologic recovery (CRh) within the first two cycles in phase 2. A total of 26 patients enrolled and 25 (96%) reported grade ≥3 adverse events (mostly cytopenias). There were no DLT. CR/CRh within two cycles was achieved by 4 of 5 patients (80%) in phase 1b and 8 of 21 patients (38%) in phase 2. Among patients with evaluable minimal residual disease, 4 (100%) in phase 1b and 3 (38%) in phase 2 had a complete MRD response. Median RFS for 8 patients who achieved CR/CRh in phase 2 was 5 (95% CI: 3.5‐6.4) months; median OS was not estimable. There were no significant associations between maximum cytokine levels or percentage of specific cell types during cycle 1 and response. Consistent with global studies, blinatumomab appeared to be safe and efficacious in Japanese adults with R/R ALL., Flow of patients through the study. (A) Phase 1b part. (B) Phase 2 part.

A 41-year-old woman presented with productive cough and exertional dyspnea. Bronchoscopy revealed an endobronchial tumor arising from the membrane proximal to the bifurcation of right upper bronchus, and the tumor was a typical carcinoid. The right main bronchus, right upper lobe bronchus, and intermediate bronchus were resected along with the tumor. Intraoperative pathological diagnosis of the bronchial stumps was negative, and bronchial reconstruction was subsequently performed. Two-thirds of the circumference of the right main bronchus and the right intermediate bronchus were anastomosed. The right upper lobe bronchus was anastomosed in an end-to-side fashion. The anastomotic site was covered by the intercostal muscles.

Background The phase 3 VIALE-A trial (NCT02993523) reported that venetoclax-azacitidine significantly prolonged overall survival compared with placebo-azacitidine in patients with newly diagnosed acute myeloid leukemia ineligible for intensive chemotherapy. Herein, efficacy and safety of venetoclax-azacitidine are analyzed in the Japanese subgroup of VIALE-A patients. Methods Eligible Japanese patients were randomized 2:1 to venetoclax-azacitidine (N = 24) or placebo-azacitidine (N = 13). Primary endpoints for Japan were overall survival and complete response (CR) + CR with incomplete hematologic recovery (CRi). Venetoclax (target dose 400 mg) was given orally once daily. Azacitidine (75 mg/m2) was administered subcutaneously or intravenously on Days 1–7 of each 28-day cycle. Results Median follow-up was 16.3 months (range, 1.0–20.3). Median overall survival was not reached with venetoclax-azacitidine (hazard ratio 0.409 and 95% confidence interval: 0.151, 1.109); overall survival estimate was higher with venetoclax-azacitidine than placebo-azacitidine at 12 (67 and 46%) and 18 months (57 and 31%), respectively. CR and CRi rates were 67% with venetoclax-azacitidine and 15% with placebo-azacitidine. Most common any-grade adverse events were febrile neutropenia (79 and 39%), thrombocytopenia (54 and 77%), constipation (54 and 54%) and decreased appetite (54 and 38%) in the venetoclax-azacitidine and placebo-azacitidine arms, respectively. Only 1 patient in the venetoclax-azacitidine arm, and no patients in the placebo-azacitidine arm, had grade 4 febrile neutropenia that led to treatment discontinuation. Conclusions This Japanese subgroup analysis of VIALE-A demonstrates comparable safety and efficacy outcomes compared with the global study and supports venetoclax-azacitidine as first-line standard-of-care for Japanese treatment-naive patients with acute myeloid leukemia who are ineligible for intensive chemotherapy.