An observational study of once-weekly carfilzomib in patients with multiple myeloma in Japan (Weekly-CAR study).

Background: The ARROW study demonstrated that once-weekly carfilzomib and dexamethasone (wKd) therapy significantly prolonged progression-free survival compared with twice-weekly carfilzomib and dexamethasone therapy in relapsed or refractory multiple myeloma patients. Aim: To describe the treatment patterns, effectiveness and safety of wKd therapy in real-world settings in Japan. Methods: We investigated data from the medical records of 126 Japanese patients with relapsed or refractory multiple myeloma. Results: The overall response rate was 66.3%. The median progression-free survival was 9.5 months. The incidence of treatment-emergent adverse events of any grade and grade ≥3 were 45.8 and 20.8%, respectively. Conclusion: There were no new or unexpected safety signals in this study. This study demonstrated the effectiveness and safety profiles of wKd therapy in Japan.

Carfilzomib became available for daily clinical practice as a drug for cancer of bone marrow (multiple myeloma) that comes back or does not respond to previous drug (relapsed or refractory). This drug was approved in the USA in 2012, and in Japan in 2016. In this study, we looked at how once-weekly carfilzomib works and how safe it is in real-life situations in Japan. We screened 126 patients with relapsed or refractory multiple myeloma in Japan. The median age of the patients was 70 years, with 25% being over 75 years. This study also included some patients who were not in the best overall health, had a history of many treatments or had heart complications. In 66.3% of patients, the cancer had disappeared or the extent of the cancer had reduced after treatment. Side effects and serious side effects occurred in 45.8 and 14.2% of patients, respectively. The most common side effects were low levels of blood platelets (9.2%), high blood pressure (5.8%), loose or watery stools (5.0%), fever (5.0%), and low levels of red blood cells (4.2%). Heart disorders occurred in five patients. But all patients recovered or improved with treatment such as blood pressure lowering drugs and diuretics. These results showed that once-weekly carfilzomib works well and is safe in real-world settings in Japan. This information can help us think about how to pick the right patients and handle heart disease risks when using carfilzomib treatment.

Acquired hemophilia A developing in the perioperative period of pancreatoduodenectomy: a report of two cases.

BACKGROUND: Acquired hemophilia A (AHA) is a rare disease characterized by a prolonged activated partial thromboplastin time (aPTT) and the production of coagulation factor VIII inhibitors. We encountered two cases of AHA in the perioperative period of pancreatoduodenectomy (PD). CASE PRESENTATION: Case 1: A 76-year-old woman with intraductal papillary mucinous carcinoma developed acute cholecystitis 5 days before PD. Despite immediate improvement in her acute cholecystitis with biliary drainage and antibiotics, her aPTT level was prolonged (55.9 s). PD was performed as scheduled. On postoperative day (POD) 2, she developed intra-abdominal hemorrhaging that required reoperation. However, intra-abdominal bleeding and concomitant anemia persisted after reoperation. On POD 13, she was diagnosed with AHA based on the detection of an inhibitor of coagulation factor VIII. Despite hemostatic and immunosuppressive treatment, including massive blood transfusion, her general condition gradually worsened due to continuous bleeding and secondary infections. She ultimately died of multiple organ failure on POD 71. Case 2: An 82-year-old man received PD for distal cholangiocarcinoma. On POD 3, a small amount of blood via abdominal drainage was observed. On POD 4, his aPTT level was prolonged (61.5 s). On POD 8, subcutaneous hemorrhaging of the median wound was observed, and corticosteroids were administered under suspicion of AHA on POD 9. On POD 15, an inhibitor of FVIII was detected, and he was diagnosed with AHA. On POD 17, the aPTT level had normalized, and an inhibitor of FVIII was undetectable. On POD 41, he was discharged without any serious hemorrhagic events. CONCLUSIONS: AHA may be more frequent than previously reported. When unexplained prolonged aPTT or bleeding symptoms are observed, it is important to keep AHA in mind during the perioperative period of invasive surgery.

Impact of Body Mass Index on 5-Year Survival Rates in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation.

Background: Cancer survival is associated with body mass index (BMI). However, the impact of patients' baseline characteristics on allogeneic hematopoietic stem cell transplantation (allo-HSCT) outcomes remains unclear. This study aimed to examine the baseline clinical factors associated with 5-year survival rates in patients undergoing allo-HSCT. Material and Methods: This was a retrospective exploratory observational study. Patients (n = 113, 52 women; average age: 55 years) who underwent allo-HSCT at the Division of Hematology and Stem Cell Transplantation, Shizuoka Cancer Center, between January 2008 and March 2015, were included in the present study. Results: Patients with low BMI (<18.5 kg/m2) had significantly lower 5-year survival rates than those with normal (18.5-24.9 kg/m2) and high (⩾25.0 kg/m2) BMI. The 5-year survival rate was poorer for patients with sarcopenia (41.5%) than that for those without sarcopenia prior to allo-HSCT (P = .05). The 5-year survival rate was poorer for patients with geriatric nutritional risk index (GNRI < 98) (34.5%) than that for those without GNRI prior to allo-HSCT (P < .01). Conclusions: Low BMI before allo-HCST pre-treatment was a predictor of 5-year survival rates in this study. Patients undergoing allo-HSCT may require nutritional interventions during pre-treatment to reduce the risk of sarcopenia and GNRI (<98), which affects their survival rates.

Examination of a nutritional treatment pathway according to pretreatment health status and stress levels of patients undergoing hematopoietic stem cell transplantation.

INTRODUCTION: This study aimed to validate hematopoietic stem cell transplantation (HSCT) treatment via a tailored nutritional pathway in myeloablative conditioning (MAC), determine its efficacy in terms of remission, and explore associations between clinical outcomes and nutritional indicators. METHODS: We included patients who underwent MAC for HSCT at the Shizuoka Cancer Center Stem Cell Transplantation between 2015 and 2019. We evaluated outcomes from the day before treatment initiation (transplant date: day 0) to day 42. RESULTS: Among the 40 MAC cases (participant characteristics: 20/40 males, mean age of 52 years, and mean body mass index of 21.9 kg/m2), we found that the percent loss of body weight and loss of skeletal muscle mass were correlated with the basal energy expenditure rate (BEE rate; r = 0.70, p<0.001 and r = 0.49, p<0.01, respectively). Based on the receiver operating characteristics curves, the cutoff value for the BEE rate in terms of weight loss was 1.1. Salivary amylase levels did not significantly change during the treatment course. Continuous variables, including oral caloric intake and performance status, showed statistically significant correlations with nutrition-related adverse events during treatment (r = -0.93, p<0.01 and r = 0.91, p<0.01, respectively). Skeletal muscle mass before treatment initiation was an independent predictive variable for reduced 2-year survival (p = 0.04). CONCLUSION: Our results support the validity of a safe nutritional pathway with a BEE rate of 1.1 for HSCT patients pretreated with MAC. Specifically, we found that this pathway could prevent weight loss in response to nutrition-related adverse events. Skeletal muscle mass before treatment was identified as an independent risk factor for reduced 2-year survival.

Safety and efficacy of anti-programmed cell death-1 monoclonal antibodies before and after allogeneic hematopoietic cell transplantation for relapsed or refractory Hodgkin lymphoma: a multicenter retrospective study.

We conducted a multicenter study on anti-programmed cell death-1 monoclonal antibodies (anti-PD-1 mAbs) before/after allogeneic hematopoietic cell transplantation (allo-HCT) for Hodgkin lymphoma. Anti-PD-1 mAbs were administered to 25 patients before allo-HCT and to 20 after allo-HCT. In pre-allo-HCT setting, the median interval from the last administration to allo-HCT was 59 days. After allo-HCT, 12 patients developed non-infectious febrile syndrome requiring high-dose corticosteroid. The cumulative incidences of grade II-IV acute graft-versus-host disease (aGvHD) were 47.1%. Eight patients who had GvHD prophylaxis with post-transplant cyclophosphamide (PTCy) had less frequent aGvHD (grade II-IV, 14.6% versus 58.8%; P = 0.086). The 1 year overall survival (OS), relapse/progression, and non-relapse mortality rates were 81.3%, 27.9%, and 8.4%. In post-allo-HCT setting, the median interval from allo-HCT to the first administration was 589 days. The overall and complete response rates were 75% and 40%. At 100 days after anti-PD-1 therapy, the cumulative incidences of grade II-IV aGvHD, moderate-to-severe chronic GvHD, and grade 3-4 immune-related toxicity were 15.0%, 30.0%, and 30.0%. While the 1 year relapse/progression rate was 47.4%, the 1 year OS probability was 89.7%. In conclusion, immune-related complications were frequent despite modifications of GvHD prophylaxis or anti-PD-1 mAb dosing. In anti-PD-1-mAb-pretreated patients, PTCy-based GvHD prophylaxis may be effective.

Benefit of Reducing Body Weight Loss with A Nutritional Support Pathway in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation.

BACKGROUND: This retrospective, historically controlled investigative study examined the benefit of a nutritional support pathway that included nutritional education before the start of conditioning and emphasized oral nutrition in response to nutrition-related adverse events in patients undergoing hematopoietic stem cell transplantation (HSCT). MATERIAL AND METHODS: Participants were patients undergoing allogeneic HSCT; 46 were in the control group (i.e., did not follow our nutritional pathway) and 36 were in the group that underwent nutritional intervention (enhanced nutrition group). We compared the following parameters between groups from the day before the start of conditioning to the day after completion of parenteral nutrition (PN): percent loss of body weight (%LBW), percent loss of skeletal muscle mass (%LSMM), and estimated basal energy expenditure (EBEE) sufficiency rate. The relationship between each parameter and %LBW was also examined. We also compared nutritional indices, gastrointestinal graft versus host disease (GvHD) grade, oral energy intake, and %LBW between groups. RESULTS: There was a relationship between %LBW, %LSMM, and EBEE sufficiency rate in both groups. Compared with the control group, the enhanced nutrition group had significantly improved energy intake amount, EBEE sufficiency rate, PN duration, and oral energy intake over time. The enhanced nutrition group also had increased oral energy intake, no difference in gastrointestinal GvHD grade, and improved %LBW compared with the control group. CONCLUSIONS: Use of our nutritional support pathway in patients undergoing HSCT may be beneficial for %LBW and gastrointestinal GvHD grade, enabling early enhanced nutritional intervention after HSCT.

Comparison of levetiracetam with phenytoin for the prevention of intravenous busulfan-induced seizures in hematopoietic cell transplantation recipients.

PURPOSE: Busulfan is used as a conditioning regimen for hematopoietic stem cell transplantation and is known to cause seizures as a side effect. As various anticonvulsant drugs have been reported, we conducted a retrospective investigation regarding the preventive effects and adverse events associated with different anticonvulsants administered alongside intravenous busulfan (ivBu) in our institution. METHODS: We targeted 104 patients who received ivBu at our institution from May 1, 2010 to April 30, 2017. We investigated the seizure prevention rate and adverse events rate under anticonvulsant prophylaxis. RESULTS: There were 70 cases (67.3%) of phenytoin administration and 34 cases (32.7%) of levetiracetam administration for anticonvulsant therapy. The seizure prevention rate was 98.6% for phenytoin and 100% for levetiracetam; seizures occurred in one out of 104 patients. There were no significant differences in the seizure prevention rate depending on the type of anticonvulsant. Further, there were no differences in adverse events. CONCLUSIONS: Anticonvulsant prophylaxis is considered necessary for safe conditioning with ivBu. Adverse events associated with the use of levetiracetam are within an acceptable range. Further, levetiracetam is considered useful as a preventive drug against seizures during ivBu administration because it is easy to administer and has ideal pharmacokinetics for supportive care.

Nutritional risk in allogeneic stem cell transplantation: rationale for a tailored nutritional pathway.

Hematopoietic stem cell transplantation carries nutrition-related risks. Therefore, nutritional therapy needs to be initiated before transplantation even takes place. We assessed nutritional risk among patients who underwent allogeneic stem cell transplantation. We assessed nutrient supply (calorie supply and protein supply) by chart review. Assessments were made from the pretreatment phase of transplantation to after the end of parenteral nutrition in 51 patients who underwent allogeneic stem cell transplantation at Shizuoka Cancer Center between 2007 and 2012. We compared nutrition-related adverse events and parameters between two groups: those in whom % loss of body weight was ≥7.5 and those in whom % loss of body weight was <7.5. A correlation was observed between changes in weight and skeletal muscle mass (r = 0.89; P < 0.0001). A weak correlation was observed between % loss of body weight and nutrient supply of calories (r = 0.517; P = 0.0001). There were significant differences between the % loss of body weight ≥7.5 group and the % loss of body weight <7.5 group in the following variables: % loss of body weight, nutrient supply from calories and protein; orally ingested nutrient supply from calories and protein; start day of oral intake; and acute graft-versus-host disease. Orally ingested calories were negatively correlated with nutrition-related adverse events in both groups. Early and customized nutritional intervention may be optimal for all patients who undergo allogeneic stem cell transplantation to ameliorate body weight loss associated with nutrition-related adverse events.

oligoclonal bands in patients with multiple myeloma: its emergence per se could not be translated to improved survival.

The emergence of oligoclonal bands (OB) has been reported in patients with multiple myeloma (MM) after stem cell transplantation (SCT) or successful chemotherapy. However, their clinical relevance remains unclear. We reviewed the clinical records of MM patients from January 2006 to May 2014. Treatment response was evaluated by International Working Group (IMWG) criteria. Serum immunofixation tests were performed at least every 3 months if the patient achieved more than very good partial response (VGPR). Free light chain (FLC) and minimal residual disease measurement by multicolor flow cytometry (MFC) were performed to evaluate the response to treatment. Among the 163 patients included in the study, 40 developed OB. Detection rates of OB in patients with complete response (CR), VGPR and partial response (PR) or less were 51.8, 36.3 and 0%, respectively. Patients with OB showed better progression-free survival (PFS) and overall survival (OS) rates than those without OB (P = 0.028 and P < 0.001, respectively). However, if the patients were limited to ≥VGPR or CR, development of OB did not affect PFS (P = 0.621 and P = 0.646, respectively) or OS (P = 0.189 and P = 0.766, respectively). OB was observed in 60% of patients after SCT, and in 36.6% of patients with more than VGPR without SCT (P < 0.001). Patients with OB tended to have less minimal residual disease than those without OB (P = 0.054) and its presence may affect the stringent CR criteria. In conclusion, the emergence of OB was seen exclusively in patients with favorable responses, but its emergence per se could not be translated to improved survival.