ALBERT

Description: Introduction: Despite a plethora of novel therapies, autologous stem cell transplant (ASCT) continues to offer a progression free survival benefit to multiple myeloma patients. At our institution, standard of care for transplant-eligible patients remains induction with cyclophosphamide, bortezomib, and decadron (CyBorD) for 4 cycles, followed by ASCT. However, limited resources for collection and the logistics of receiving late referrals from outside centers often result in patients receiving additional cycles of treatment prior to transplant. We sought to determine whether the administration of additional induction chemo led to increased peri-transplant morbidity. Methods: With REB approval, chart review was done for myeloma patients receiving an ASCT between 2007 and 2017. Only patients receiving induction with CyBorD or bortezomib-decadron on a like schedule were included in analysis. Patients received pre-ASCT conditioning of high-dose melphalan (93.5%) or busulfan-melphalan (6.5%). Data collected included patient's age, gender, myeloma subtype, ISS score, and cytogenetics, as well as the number of induction cycles received and hematopoietic cell transplantation-specific co-morbidity index (HCT-CI). The primary endpoint assessed was median length of hospital stay (LOS) post-infusion. Secondary end-points included time to engraftment, ICU transfer rate, infection rate, organ-specific toxicity, 100-day mortality, and response as measured by VGPR rate at 100 days. Patients were grouped into those who received 2-4 cycles vs. 5-9 cycles of induction. Results: Fifty-three patients received 2-4 cycles of induction and 54 received 5-9. Median age was 61 for both groups, gender was well-matched (53% vs. 57% male), and HCT-CI ≥ 3 was similar (26% vs. 31%).The only significant difference between groups was the subtype of myeloma, with the 2-4 group having 30.1% light chain disease (vs. 14.8%) and 39.6% IgG subtype (vs. 61.1%) (p = 0.026). Median LOS post-infusion was 20 days in the 2-4 group and 17 days in the 5-9 group. Median time to engraftment was 12 days in both (range 9-21 in 2-4 group, 10-20 in 5-9 group). ICU transfer was needed in 4 (7.5%) and 6 (11.1%) patients in the respective groups, and there were two deaths in the 5-9 group (one of sepsis at d+16 and one of multi-organ failure at d+46). Both patients had HCT-CI scores of 5, and the differences in ICU and mortality rates were not statistically significant. There were no significant differences in measurable toxicity. Documented infection or febrile neutropenia occurred in 92.5% vs. 88.9% (p = 0.53); acute kidney injury in 20.8% vs. 11.1% (p= 0.17); and acute liver injury in 24.5% vs. 14.8% (p = 0.21). Among evaluable patients, 84.6% achieved VGPR or better in the 2-4 group and 78.4% in the 5-9 group, although the latter had a higher number of patients with high-risk cytogenetics by FISH (6 vs. 10 with t(4;14) or 17p-). Discussion: Evidence for a precise number of cycles of induction prior to ASCT is scarce. A recent study by Charaborty et. al.(BJHJul 2018) showed that median PFS and OS were similar between patients who received ≤ 4 months vs. 〉 4 months of induction. 39% of their patients received bortezomib-based induction without lenalidomide, akin to our regimen. Likewise, our study showed no significant difference in VGPR rates at 100 days, an endpoint used at our center as one criterion for determining the need for tandem transplant and potential increased chemotherapy exposure for the patient. Our overall VGPR rate for the group of 81.6% is comparable to previously published results, suggesting our population is representative of a typical myeloma cohort. Most importantly, our data suggests no increase in peri-transplant toxicity as a result of the additional induction chemotherapy burden. In fact, there was a surprising trend towards decreased organ toxicity and shorter hospital stay, and the only two early deaths occurred in high-risk patients. Among the 17 patients who received the heaviest induction burden (7-9 cycles), there were no deaths and only 1 ICU transfer. While there did not appear to be any long-term benefit to greater induction length, our study provides reassurance that it is safe to continue CyBorD induction past the intended 4 cycles without compromising patient safety at the time of transplant. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

Description: Abstract 4895 Background: The treatment of primary central nervous system lymphoma (PCNSL) is characterized by high rates of toxicity and intracranial relapse despite initial response. High-dose methotrexate (HD-MTX), with or without cranial irradiation, has become the standard of care; combining this with other chemotherapeutic agents has improved complete remission rates but at the expense of increased treatment-related adverse events, particularly haematologic and neurologic toxicity. Cytarabine has been used in combination with etoposide (CYVE) as a salvage therapy for patients who have been refractory to or relapsed after HD-MTX-based regimens (Soussain C et al, J. Clin. Oncol. 2001; Soussain C et al, J. Clin. Oncol. 2008). In these studies, cytarabine was given as an infusion at a dose of 50mg/m2/d over 12 hours on days 1–5, and at a dose of 2g/m2/d over 3 hours on days 2–5 with etoposide at 200mg/m2/d on days 2–5. Both responders and non-responders were eligible to proceed to autologous stem cell transplant (autoSCT) using a conditioning regimen of thiotepa 250mg/m2/d on days -9 to -7, busulfan 10mg/kg total dose po or 8mg/kg total dose iv over days -6 to -4, and cyclophosphamide 60 mg/m2/d on days -3 to -2. Median OS was 58.6 months in patients able to undergo autoSCT, but with significant neurotoxicity that may have been related in part to prior therapies. Methods and Results: Given its excellent CNS penetration, CYVE may be an effective regimen in previously untreated patients, with lower risk of neurotoxicity. We have used CYVE as a first-line therapy for patients with PCNSL who are potentially eligible for subsequent autoSCT. Between January 1, 2005 and December 31, 2009, 7 patients with a diagnosis of PCNSL were treated with first-line CYVE using the regimen described above. All were HIV negative, showed no disease outside of the CNS on bone marrow biopsy and staging CT or PET scan, and had biopsy-proven PCNSL with diffuse large B-cell histology. Median age was 55 (42-61) with 4 female and 3 male patients. Median International Extranodal Lymphoma Study Group Prognostic Index score was 2 (0-2), although in actuality may have been higher, as 4 patients were not able to undergo lumbar puncture at diagnosis. ECOG status was 〈 2 in 3 patients, ≥ 2 in 3 patients, and not documented in 1 case. Patients received a median of 2 cycles of CYVE (1-3), with 2 receiving concurrent rituximab and the 1 patient with intra-ocular lymphoma receiving post-adjuvant orbital radiation. No cranial radiation was administered. Five patients achieved CR and proceeded to autoSCT. Two patients had a PR but later died of progressive disease at day +48 and day +117, respectively. In both cases, however, the patients were suspected of having disease long before they were treated with CYVE. The first had presented 3 years prior to the diagnosis with a solitary brain lesion that resolved with decadron monotherapy before pathologic documentation. The second had had a brain biopsy that failed to show malignant disease 4 months before the PCNSL diagnosis was confirmed and treatment initiated. Median OS and PFS for the group have not yet been reached with mean follow-up of 657 days. Among the 5 patients who achieved CR, all patients remain alive in CR with a mean follow-up of 841 days (320-1262 days), or 28 months. Toxicities included at least 1 episode of febrile neutropenia in all 7 patients, 2 possible but unconfirmed cases of pulmonary aspergillosis, 2 cases of drug-induced hepatitis (with ALT 〉 3x ULN), 1 case of toxic epidermal necrolysis secondary to imipenem use during an episode of febrile neutropenia, 1 small bowel obstruction requiring surgical intervention, and 1 case of late grade 2 neurotoxicity presenting 3 years after treatment. Conclusions: In this small cohort of patients, first-line CYVE has shown to be highly effective (ORR 100%, CR 71%) with minimal long-term toxicity compared to that which is seen using it as a salvage therapy. When followed by autoSCT, long-term survival with preserved quality of life may be possible. A prospective study would be necessary to confirm these initial results in practice. Disclosures: No relevant conflicts of interest to declare.

Description: Deep- and reinforcement-learning techniques have increasingly required large sets of real data to achieve stable convergence and generalization, in the context of image-recognition, object-detection or motion-control strategies. On this subject, the research community lacks robust approaches to overcome unavailable real-world extensive data by means of realistic synthetic-information and domain-adaptation techniques. In this work, synthetic-learning strategies have been used for the vision-based autonomous following of a noncooperative multirotor. The complete maneuver was learned with synthetic images and high-dimensional low-level continuous robot states, with deep- and reinforcement-learning techniques for object detection and motion control, respectively. A novel motion-control strategy for object following is introduced where the camera gimbal movement is coupled with the multirotor motion during the multirotor following. Results confirm that our present framework can be used to deploy a vision-based task in real flight using synthetic data. It was extensively validated in both simulated and real-flight scenarios, providing proper results (following a multirotor up to 1.3 m/s in simulation and 0.3 m/s in real flights).

Description: The development of autonomous vehicles for urban driving has seen rapid progress in the past 30 years. This paper provides a summary of the current state of the art in autonomous driving in urban environments, based primarily on the experiences of the authors in the 2007 DARPA Urban Challenge (DUC). The paper briefly summarizes the approaches that different teams used in the DUC, with the goal of describing some of the challenges that the teams faced in driving in urban environments. The paper also highlights the long-term research challenges that must be overcome in order to enable autonomous driving and points to opportunities for new technologies to be applied in improving vehicle safety, exploiting intelligent road infrastructure and enabling robotic vehicles operating in human environments.

Description: Viewgraphs on control design for the Space Engineering Research Center experimental testbeds are presented. Topics covered include: SISO control design and results; sensor and actuator location; model identification; control design; experimental results; preliminary LAC experimental results; active vibration isolation problem statement; base flexibility coupling into isolation feedback loop; cantilever beam testbed; and closed loop results.

Description: Viewgraphs on the application of controlled structures technology (CST) to adaptive optics are presented. Topics covered include: a typical large optical system (LDR); overview of current optical programs; typical adaptive optics system; actuation approaches for deforming a mirror; control approach comparison; control structure interaction (CSI) control bandwidth limitations; applications of CST concepts to optics; distributed control approaches; quasistatic error correction; low authority control (LAC); and high authority control (HAC) design methodology.

Description: Viewgraphs on finite element model and identification procedure are presented. Topics covered include: interferometer finite element model; testbed mode shapes; finite element model update; identification procedure; shaker locations; data analysis; modal frequency and damping comparison; computational procedure; fit comparison; residue analysis; typical residues; identification/FEM residual comparison; and pathlength control using isolation mounts.