Safety, pharmacokinetics, and efficacy of belantamab mafodotin monotherapy in Japanese patients with relapsed or refractory multiple myeloma: DREAMM-11.

Belantamab mafodotin, a B-cell maturation antigen-targeting antibody-drug conjugate (ADC), was investigated in Japanese patients with relapsed/refractory multiple myeloma in Part 1 of the phase I DREAMM-11 study. Patients who had received ≥ 2 prior lines of therapy including a proteasome inhibitor and immunomodulatory agent were eligible. Eight patients received belantamab mafodotin monotherapy at 2.5 mg/kg (n = 4) or 3.4 mg/kg (n = 4) by intravenous infusion every 3 weeks on day 1 of each cycle until disease progression or unacceptable toxicity. Primary objectives were tolerability and safety, and secondary objectives included pharmacokinetics (PK) and efficacy. The most common Grade ≥ 3 adverse event was thrombocytopenia/platelet count decreased (2.5 mg/kg cohort, 100% [4/4]; 3.4 mg/kg cohort, 75% [3/4]), and no dose-limiting toxicities were observed. Ocular events, including keratopathy findings, were observed in most patients (2.5 mg/kg cohort, 100% [4/4]; 3.4 mg/kg cohort, 75% [3/4]) and were managed with dose modifications. All resolved within the study period. Overall response rates were 50% (2/4) in the 2.5 mg/kg cohort and 25% (1/4) in the 3.4 mg/kg cohort. Although PK profiles in Japanese patients varied, individual exposures overlapped with previous results in Western populations. Belantamab mafodotin monotherapy was generally well-tolerated and demonstrated clinical activity at both doses.

Cerebral hemodynamics during neonatal transition according to mode of delivery.

Cerebral haemodynamics during the immediate transition period in neonates may differ depending on whether delivery is vaginal or by caesarean section. However, these differences have never been confirmed by near-infrared time-resolved spectroscopy (TRS). Therefore, the purpose of this study was to compare cerebral blood volume (CBV) and cerebral haemoglobin oxygen saturation (ScO2) between healthy term neonates by mode of delivery. Subjects were 31 healthy term neonates who did not require resuscitation. Thirteen neonates were delivered vaginally (VD group) and 18 were delivered by elective caesarean section (CS group). Absolute oxyhaemoglobin, deoxyhaemoglobin, and total haemoglobin concentrations were measured continuously by TRS; oxyHb × 100/totalHb (ScO2) (%) and CBV (mL/100 g brain tissue) were also calculated. Measurements were started as soon as possible after birth, obtained from 1 to 2 min after birth, and continued until 15 min after birth. CBV was significantly higher in the VD group than in the CS group in the 4 min after birth but not thereafter. There were no significant between-group differences in ScO2 and SpO2. These findings indicate that there is a difference in cerebral haemodynamic patterns in the first 4 min after delivery between term neonates by mode of delivery when CBV is monitored by TRS.

Immature granulocyte fraction in the peripheral blood is a practical indicator for mobilization of CD34(+) cells.

We propose a simple parameter that improves prediction of the number of CD34(+) cells in blood cells collected by apheresis for autologous peripheral blood stem cell (PBSC) transplantation following administration of granulocyte colony-stimulating factor. The percentage of immature granulocytes including myeloblasts, promyelocytes, myelocytes, and metamyelocytes (LSI for left-shift index) immediately prior to the start of each apheresis correlated with the number of CD34(+) cells in PBSC collections (r = 0.79, P < 0.0001, Y = 0.227X - 0.99, R(2) = 0.623) much better than did the white blood cell count (r = 0.07), currently the most commonly used predictor in deciding the initiation of apheresis. We then used receiver operating characteristic (ROC) curves to determine a cutoff point for LSI to prevent unnecessary apheresis. At LSI > 7.5, sensitivity and specificity of cutoff points in the probability of obtaining >1.0 x 10(6) CD34(+) cells/kg BW were 93.3% and 94.3% (95% CI, 91.4-100.0%), respectively. When LSI reaches 15.25, nearly 100% of apheresis will attain the target CD34(+) cell dose. These findings indicate that LSI is a useful and simple method for predicting the yield of CD34(+) cells before the start of PBSC collection and avoiding unnecessary apheresis.