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In the phase 3 ALCYONE study, daratumumab plus bortezomib/melphalan/prednisone (D-VMP) versus bortezomib/melphalan/prednisone (VMP) significantly improved progression-free survival (PFS) and overall survival (OS) in transplant-ineligible, newly diagnosed multiple myeloma (NDMM) patients. We present a subgroup analysis of ALCYONE by patient frailty status. Frailty assessment was performed retrospectively using age, Charlson comorbidity index, and baseline Eastern Cooperative Oncology Group performance status score. Patients were classified as fit (0), intermediate (1), or frail (≥2); a nonfrail category combined fit and intermediate patients. Among randomized patients (D-VMP, n = 350; VMP, n = 356), 391 (55.4%) were nonfrail (D-VMP, 187 [53.4%]; VMP, 204 [57.3%]) and 315 (44.6%) were frail (163 [46.6%]; 152 [42.7%]). After 40.1-months median follow-up, nonfrail patients had longer PFS and OS than frail patients, but benefits of D-VMP versus VMP were maintained across subgroups: PFS nonfrail (median, 45.7 vs. 19.1 months; hazard ratio [HR], 0.36; P < .0001), frail (32.9 vs. 19.5 months; HR, 0.51; P < .0001); OS nonfrail (36-month rate, 83.6% vs. 74.5%), frail (71.4% vs. 59.0%). Improved greater than or equal to complete response and minimal residual disease (10)-negativity rates were observed for D-VMP versus VMP across subgroups. The 2 most common grade 3/4 treatment-emergent adverse events were neutropenia (nonfrail: 39.2% [D-VMP] and 42.4% [VMP]; frail: 41.3% and 34.4%) and thrombocytopenia (nonfrail: 32.8% and 36.9%; frail: 36.9% and 39.1%). Our findings support the clinical benefit of D-VMP in transplant-ineligible NDMM patients enrolled in ALCYONE, regardless of frailty status.

Claudia Djambas Khayat,1 Genadi Iosava,2 Irina Romashevskaya,3 Oleksandra Stasyshyn,4 Marta Julia Lopez,5 Maria Teresa Pompa,6 Tobias Rogosch,7 Wilfried Seifert7 1Hospital Hôtel Dieu de France, Saint Joseph University, Beirut, Lebanon; 2Joint Stock Hematology and Transfusiology Research Institute, Tbilisi, Georgia; 3Republican Research Centre of Radiation Medicine and Human Ecology, Gomel, Belarus; 4Institute of Blood Pathology and Transfusion Medicine, Lviv, Ukraine; 5Guatemala City Hospital Roosevelt, Guatemala, Guatemala; 6Monterrey Nuevo Leon OCA Hospital (MIRC), Monterrey Nuevo Leon, Mexico; 7CSL Behring, Clinical Research and Development, Marburg, GermanyCorrespondence: Claudia Djambas KhayatHospital Hôtel Dieu de France, Saint Joseph University, Beirut, LebanonTel +9611613027Email claudiakhayat@yahoo.frBackground: Plasma-derived von Willebrand factor/factor VIII (pdVWF/FVIII; VONCENTO®, CSL Behring) is a high-concentration, low-volume, high-purity concentrate, with a high level of VWF high-molecular-weight multimers and a VWF/FVIII ratio of ∼ 2.4:1.Methods: This study (NCT01229007) investigated the pharmacokinetics (PK), efficacy and safety of pdVWF/FVIII in 35 previously treated (minimum 20 exposure days [EDs]) pediatric patients (< 12 years) with severe hemophilia A. PK was evaluated with a single 50 IU FVIII/kg dose of pdVWF/FVIII. Efficacy and safety analyses were performed during on-demand treatment (n=17) or prophylaxis (n=18) for up to 100 EDs with a maximum study duration of 12 months.Results: PK profiles were similar for patients aged < 6 years and those aged 6– 12 years, and, as expected, the youngest patients had an increased clearance. On-demand patients reported 320 non-surgical bleeding (NSB) events and received a median number of 29.0 infusions (median dose 34.2 IU FVIII/kg). Hemostatic efficacy was assessed by the investigator as excellent/good in all cases (24%/76%). The 18 patients

[Background]: In the phase 3 ALCYONE study, daratumumab plus bortezomib/melphalan/prednisone (D-VMP) versus bortezomib/melphalan/prednisone (VMP) significantly improved progression-free survival (PFS) and overall survival (OS) in transplant-ineligible, newly diagnosed multiple myeloma (NDMM) patients. We present a subgroup analysis of ALCYONE by patient frailty status., [Patients and Methods]: Frailty assessment was performed retrospectively using age, Charlson comorbidity index, and baseline Eastern Cooperative Oncology Group performance status score. Patients were classified as fit (0), intermediate (1), or frail (≥2); a nonfrail category combined fit and intermediate patients., [Results]: Among randomized patients (D-VMP, n = 350; VMP, n = 356), 391 (55.4%) were nonfrail (D-VMP, 187 [53.4%]; VMP, 204 [57.3%]) and 315 (44.6%) were frail (163 [46.6%]; 152 [42.7%]). After 40.1-months median follow-up, nonfrail patients had longer PFS and OS than frail patients, but benefits of D-VMP versus VMP were maintained across subgroups: PFS nonfrail (median, 45.7 vs. 19.1 months; hazard ratio [HR], 0.36; P < .0001), frail (32.9 vs. 19.5 months; HR, 0.51; P < .0001); OS nonfrail (36-month rate, 83.6% vs. 74.5%), frail (71.4% vs. 59.0%). Improved greater than or equal to complete response and minimal residual disease (10−5)-negativity rates were observed for D-VMP versus VMP across subgroups. The 2 most common grade 3/4 treatment-emergent adverse events were neutropenia (nonfrail: 39.2% [D-VMP] and 42.4% [VMP]; frail: 41.3% and 34.4%) and thrombocytopenia (nonfrail: 32.8% and 36.9%; frail: 36.9% and 39.1%)., [Conclusion]: Our findings support the clinical benefit of D-VMP in transplant-ineligible NDMM patients enrolled in ALCYONE, regardless of frailty status.

Guenter Auerswald,1 Claudia Djambas Khayat,2 Oleksandra Stasyshyn,3 Genadi Iosava,4 Irina Romashevskaya,5 Marta Julia López,6 Wilfried Seifert,7 Tobias Rogosch7 1Hess Kinderklinik, Klinikum Bremen-Mitte, Bremen, Germany; 2Hotel Dieu de France Hospital, St Joseph University, Beirut, Lebanon; 3Institute of Blood Pathology and Transfusion Medicine, Academy of Medical Sciences of Ukraine, Lviv, Ukraine; 4Institute for Hematology and Transfusiology, Tbilisi, Georgia; 5Republican Research Centre for Radiation Medicine and Human Ecology, Gomel, Belarus; 6Hematology, Hospital Roosevelt, Guatemala, Guatemala; 7Clinical Development, CSL Behring, Marburg, GermanyCorrespondence: Guenter AuerswaldHess Kinderklinik, Klinikum Bremen-Mitte, Bremen, GermanyTel +49 176-10113362Email guenterauerswald@aol.comPurpose: Formulation V (VONCENTO®) is a plasma-derived high-concentration/low-volume, high-purity von Willebrand factor (VWF)/factor VIII (FVIII) concentrate, originally indicated for von Willebrand disease (VWD) in adults and adolescents. This multicenter, open-label study (SWIFTLY-VWD) evaluated the pharmacokinetics (PK), as well as hemostatic efficacy and safety, of Formulation V in pediatric patients (< 12 years) with severe VWD requiring treatment or prophylaxis of bleedings.Methods: PK investigations were performed following one dose of Formulation V at Day 1 and 180. Nonsurgical bleeds were analyzed, while hemostatic efficacy was graded as excellent/good/moderate/none. Safety assessments included adverse events, and presence of VWF and/or FVIII inhibitors.Results: Formulation V was administered as on-demand (N=13) or prophylaxis therapy (N=4) for 12 months (< 6 years, N=9; 6 to < 12 years, N=8). PK parameters for VWF markers were generally comparable to adults but showed lower VWF:ristocetin cofactor (RCo) exposure. Incidence of major bleeds was lower for prophylaxis (3.3%) than on-demand therapy (27.1%); joint bleeds were also lower (

BACKGROUND: The combination of bortezomib, melphalan, and prednisone is a standard treatment for patients with newly diagnosed multiple myeloma who are ineligible for autologous stem-cell transplantation. Daratumumab has shown efficacy in combination with standard-of-care regimens in patients with relapsed or refractory multiple myeloma. METHODS: In this phase 3 trial, we randomly assigned 706 patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation to receive nine cycles of bortezomib, melphalan, and prednisone either alone (control group) or with daratumumab (daratumumab group) until disease progression. The primary end point was progression-free survival. RESULTS: At a median follow-up of 16.5 months in a prespecified interim analysis, the 18-month progression-free survival rate was 71.6% (95% confidence interval [CI], 65.5 to 76.8) in the daratumumab group and 50.2% (95% CI, 43.2 to 56.7) in the control group (hazard ratio for disease progression or death, 0.50; 95% CI, 0.38 to 0.65; P<0.001). The overall response rate was 90.9% in the daratumumab group, as compared with 73.9% in the control group (P<0.001), and the rate of complete response or better (including stringent complete response) was 42.6%, versus 24.4% (P<0.001). In the daratumumab group, 22.3% of the patients were negative for minimal residual disease (at a threshold of 1 tumor cell per 105 white cells), as compared with 6.2% of those in the control group (P<0.001). The most common adverse events of grade 3 or 4 were hematologic: neutropenia (in 39.9% of the patients in the daratumumab group and in 38.7% of those in the control group), thrombocytopenia (in 34.4% and 37.6%, respectively), and anemia (in 15.9% and 19.8%, respectively). The rate of grade 3 or 4 infections was 23.1% in the daratumumab group and 14.7% in the control group; the rate of treatment discontinuation due to infections was 0.9% and 1.4%, respectively. Daratumumab-associated infusion-relate