AUGMENT : a phase III study of lenalidomide plus rituximab versus placebo plus rituximab in relapsed or refractory indolent lymphoma

PURPOSE Patients with indolent non-Hodgkin lymphoma typically respond well to first-line immunochemotherapy. At relapse, single-agent rituximab is commonly administered. Data suggest the immunomodulatory agent lenalidomide could increase the activity of rituximab. METHODS A phase III, multicenter, randomized trial of lenalidomide plus rituximab versus placebo plus rituximab was conducted in patients with relapsed and/or refractory follicular or marginal zone lymphoma. Patients received lenalidomide or placebo for 12 cycles plus rituximab once per week for 4 weeks in cycle 1 and day 1 of cycles 2 through 5. The primary end point was progression-free survival per independent radiology review. RESULTS A total of 358 patients were randomly assigned to lenalidomide plus rituximab (n = 178) or placebo plus rituximab (n = 180). Infections (63% v 49%), neutropenia (58% v 23%), and cutaneous reactions (32% v 12%) were more common with lenalidomide plus rituximab. Grade 3 or 4 neutropenia (50% v 13%) and leukopenia (7% v 2%) were higher with lenalidomide plus rituximab; no other grade 3 or 4 adverse event differed by 5% or more between groups. Progression-free survival was significantly improved for lenalidomide plus rituximab versus placebo plus rituximab, with a hazard ratio of 0.46 (95% CI, 0.34 to 0.62; P < .001) and median duration of 39.4 months (95% CI, 22.9 months to not reached) versus 14.1 months (95% CI, 11.4 to 16.7 months), respectively. CONCLUSION Lenalidomide improved efficacy of rituximab in patients with recurrent indolent lymphoma, with an acceptable safety profile

Research Activities on Venus Atmosphere Balloon Observation Mission

This presentation was part of the session : Probe Missions to the Giant Planets, Titan and VenusSixth International Planetary Probe WorkshopA feasibility study of the small Venus entry capsule and the scientific observation by the water-vapor balloon are described in this paper. Though Venus is the nearest planet to the Earth, it is still filled with mysteries and surprises. The atmosphere observation under the thick cloud on the venusian surface is of great scientific interests. Because a super-pressure type of the balloon can travel long time a wide area by strong winds on the Venus, it is considered to be of prime candidate for the atmosphere observations. A water-vapor super-pressure balloon is advantageous to obtain buoyancy force in the hot Venus atmosphere. At the entry to the Venus, the liquid-phase water is adhered to a number of the water-absorption films layered inside of the outer sealing film. The heat required for the water vaporization is supplied from the ambient environment during the ascending phase. Recently, IC chips, batteries, and solar arrays that function under the high-temperature environment ranging 180 to 220 ?C have been developed and been in practical use. By use of solar arrays, the electric power is supplied to the onboard instruments without any extra cooling system, which enables long-term observation. Then the target altitude is determined to be from 35 to 37 km considering the operation range of the high-temperature electronics. A small entry capsule with the 20m-long water-vapor balloon accommodated in it is separated from a 150kg small spacecraft and carries out direct entry from the interplanetary transfer orbit at the velocity of 11.5 km/s. The capsule releases the balloon at the appropriate altitude after passing through the aerodynamic heating corridor. Total weight of the capsule is about 30 kg containing balloon and observation instruments with weight of 10kg.Japan Aerospace Exploration Agency ; Institute of Space and Astronautical Scienc

Efficacy and safety of tisagenlecleucel in Japanese adult patients with relapsed/refractory diffuse large B-cell lymphoma

Background Tisagenlecleucel demonstrated a high rate of durable response in adult patients with relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) in the pivotal global phase 2 JULIET study. Here, we report the efficacy and safety of tisagenlecleucel in the Japanese subgroup. Methods JULIET (NCT02445248) is a single-arm, open-label, multicenter, phase 2 study involving adult patients with r/r DLBCL who either relapsed after or were ineligible for autologous stem cell transplant. Primary endpoint was best overall response rate (ORR; complete response [CR] + partial response [PR]) as judged by an independent review committee. Results In Japan, of 17 patients enrolled, 9 were infused with tisagenlecleucel and completed >= 3 months of follow-up. Best ORR was 77.8% (7/9; 95% confidence interval, 40.0-97.2), with 5 patients (55.6%) in CR and 2 (22.2%) in PR. Cytokine release syndrome (CRS) occurred in 6 patients (66.7%), with grade 3 CRS in 2 patients (Penn grading scale). Two patients received tocilizumab. Two deaths (22.2%) occurred more than 30 days after tisagenlecleucel infusion due to disease progression, neither of which were related to tisagenlecleucel. Conclusion Tisagenlecleucel showed a high best ORR with a manageable safety profile, thus offering a new treatment option in selected Japanese patients with r/r DLBCL

Autologous Stem Cell Transplantation with PCR-Negative Graft Would Be Associated with a Favorable Outcome in Core-Binding Factor Acute Myeloid Leukemia

Although core-binding factor acute myeloid leukemia (CBF-AML) is generally considered to be a low-risk form of AML, the survival rate is still 50% to 60%. To evaluate the effectiveness of autologous stem cell transplantation (ASCT) with a PCR-negative graft we analyzed a series of consecutive CBF-AML patients. Between 1997 and 2006, 18 patients aged <60 years were referred under a diagnosis of CBF-AML. Peripheral blood stem cells (PBSC) were collected after a second or further course of postremission therapy. When >2.0 × 106/kg CD34-positive cells with minimal residual disease (MRD) undetectable by nested polymerase chain reaction (PCR) had been collected, ASCT was performed with busulfan, etoposide, and cytarabine combined with granulocyte colony-stimulating factor. Event-free survival (EFS) and complications of ASCT were then assessed. Fourteen of the 18 patients received ASCT. The median observation period was 4.4 years. The 5-year EFS was 93% for ASCT patients, despite the presence of adverse factors. In 8 of 10 patients who had detectable MRD in the bone marrow before ASCT, MRD became undetectable after ASCT. Neutrophils recovered promptly within 2 weeks, but platelets recovered relatively slowly. Half of the patients suffered from varicella zoster virus infection. Although 1 case of myelodysplastic syndrome occurred, there was no case of relapse. ASCT with a PCR-negative graft was associated with excellent EFS. For patients with CBF-AML, especially with adverse factors or remnant MRD in the bone marrow, this strategy is the treatment of choice