26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15–20 July 2017

This work was produced as part of the activities of FAPESP Research,\ud Disseminations and Innovation Center for Neuromathematics (grant\ud 2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud supported by a CNPq fellowship (grant 306251/2014-0)

Lenalidomide Is Effective Therapy for Relapse After Allogeneic Stem Cell Transplant for Multiple Myeloma.

Abstract 3064 Allogeneic stem cell transplantation (Allo-SCT) can result in long-term remissions in patients with multiple myeloma although it9s overall role in disease management remains controversial. Patients who relapse after AlloSCT have limited treatment options. We evaluated the response and tolerance of lenalidomide monotherapy administered to patients with multiple myeloma who progressed or relapsed by EBMT criteria after Allo-SCT. Patients were required to have an ECOG PS of ≤2, ANC ≥1.5 × 109/l, Plts ≥50 × 109/l, creatinine ≤2, bilirubin ≤1.5, SGOT and SGPT ≤2 times ULN. Patients were allowed to take prednisone for acute GVHD but were excluded for GVHD ≥ grade 3. The initial starting dose of lenalidomide was 25 mg orally for 21 of 28 days. Dose reductions after cycle 1 were allowed for neutropenia, thrombocytopenia or other dose related toxicities. Eighteen patients, 5 female, and median age of 48 years (range 28–61) enrolled a median of 12 months (range 3–104) following transplant. Patients were transplanted from 11 matched related donors, 6 matched unrelated donors and 1 mismatched unrelated donor. Conditioning regimens were, fludarabine, 2Gy TBI for 16 and busulfan, melphalan for 1. One patient had 2 allografts from the same donor; the first with cyclophosphamide, fludarabine, the second after intermediate dose melphalan. Treatment duration of lenalidomide was a median of 8 months (range 1–51). Common grade 1–2 adverse events included diarrhea (17%) or constipation (11%), fatigue (17%), myalgias (17%), nausea (11%) and neuropathy (11%). Ten patients required dose reductions to 5–20 mg at a median of 3 cycles (range 1–12); 8 for neutropenia; 1 for thrombocytopenia, and 1 for myalgias and weakness. Serious adverse events N=5, included H1N1 influenza (2), bacterial pneumonia (2), and fever, myalgia and hypoxia. In addition, 2 patients died at 3 and 5 months of GVHD that occurred within 1 month of dosing. One death was gastrointestinal GVHD, the second from liver GVHD in a patient who was enrolled but later deemed ineligible due to elevated SGOT and SGPT by the time of study entry. These were the only 2 patients who discontinued lenalidomide due to GVHD. Three patients were on prednisone 0.5–1 mg/kg for 2, 2, and 11 months for GVHD, but only 1 patient was started on prednisone after initiation of lenalidomide. These results are in contrast to a reported 47% rate of discontinuation of lenalidomide used for maintenance after allografting due to GVHD (Kneppers, et al. Blood 118:2413, 2011) The differences between the two trials may result from the later start of lenalidomide administration in our trial (12 months v. 3 months). Best responses included CR (7), VGPR (1), PR (3), MR (1) and SD (2) for an overall response rate (≥PR) of 61%. Nine patients discontinued therapy due to PD at 1–15 months. Five patients have died from PD. Seven patients remain on therapy at a median of 33 months (range 8–51), 5 in CR. Lenalidomide for relapse of multiple myeloma after allografting can result in extended disease control in 38% of patients. Disclosures: Bensinger:Celgene: Consultancy, Honoraria, Research Funding

AL Amyloidosis Complicated by Persistent Oral Bleeding

A case of amyloid light chain (AL) amyloidosis is presented here with uncontrolled bleeding after a nonsurgical dental procedure, most likely multifactorial in nature, and consequently treated with a multidisciplinary approach

Venetoclax and Decitabine for T/Myeloid Mixed-Phenotype Acute Leukemia Not Otherwise Specified (MPAL NOS)

T/myeloid mixed-phenotype acute leukemia not otherwise specified (MPAL NOS) is an uncommon and aggressive leukemia without well-established treatment guidelines, particularly when relapsed. Venetoclax plus a hypomethylating agent offers a promising option in this situation since studies support its use in both acute myeloid and, albeit with fewer data to date, acute T-cell-lymphoblastic leukemias. We report the successful eradication of T/myeloid MPAL NOS relapsed after allogeneic stem cell transplant with venetoclax plus decitabine. A consolidative allogeneic stem cell transplant from a second donor was subsequently performed, and the patient remained without evidence of disease more than one year later. Further investigation is indicated to evaluate venetoclax combined with hypomethylating agents and/or other therapies for the management of T/myeloid MPAL NOS

Improved Stem Cell Transplant Related Mortality for AL Amyloidosis At a Single Transplant Center

Abstract Abstract 2016 The role of AHSCT in AL amyloidosis is controversial. There is evidence that AHSCT offers long term disease control with high organ response rates, however, the only randomized phase III trial comparing transplant with conventional melphalan and dexamethasone therapy deemed transplant inferior. Better understanding of risk stratification for SCT candidacy has resulted in TRM rates are as low as 5.6% in some series. The goal of the current study was to evaluate the TRM rate for all consecutive patients who have undergone AHSCT for AL amyloidosis at institution. Special attention in evaluation of any detectable differences in TRM over the time period of this review was a major goal of this project. Retrospective review was performed of all patients with primary AL amyloidosis who have undergone AHSCT at our institution. The database captured patients from December 2001 and our study includes patients through February 2012. Patients who were diagnosed with secondary amyloidosis by the stem cell transplant service and/or referring oncologist were excluded. TRM was defined as death from any cause within 100 days post stem cell infusion. We then evaluated data from the entire cohort and divided it into two different time periods: 2001–2006 and 2007–2012. Thirty-nine patients had an initial AHSCT during the study period. Nine patients were enrolled in the SWOG 0115 trial which comprised tandem autoSCT using 100 mg/m2 of melphalan conditioning 3–6 months apart. Of those, 6/9 (66%) had both transplants. For purposes of this abstract we report on the data resulting from first transplantation only for patients in the SWOG 0115 trial. The median age at transplant for the entire cohort was 57.6 years old (39–74). Males represent 64% of the patients. Most of the patients had symptomatic involvement of one organ (48.7%) with 23% having more than 2 organs involved. There were 14 patients transplanted in the 2001–2006 period and 25 patients in the 2007–2012 period. Overall TRM for 2001–2012 was 5.1%. During the 2001–2006 period TRM was 14% (2/14 patients). No TRM occurred for patients transplanted from 2007–2012. Overall survival (OS) improved when separately comparing the two study periods. Overall survival was 64% at 3 years in the 2001–2006 cohort and 92% at 3 years in the 2007–2012 cohort. Patients in the 2007–2012 cohort include all patients enrolled to SWOG 0115. Sixty percent of patients reported for that period received Univariate analysis of risk factors affecting improved OS identified year of transplant (>2006; p=0.03), number of treatments pre-transplant (>1; p=0.04), and time from diagnosis to transplant (>4mo; p=0.05) as factors associated with improved survival. Number of organs involved (>1; p=0.06) showed a trend towards worse survival. In conclusion, our single institution data demonstrates a reduction in TRM over the past 5 years. Reasons for improvement in TRM are under investigation and may include better risk stratification, better supportive care (including frequent hospitalization for cardiac monitoring in high-risk patients) and improvement in pre-AHSCT performance status for those patients receiving induction therapy with novel agents. Download : Download high-res image (19KB) Download : Download full-size image Figure: . Comparison of overall survival of patients with AL amyloidosis after autologous stem cell transplant based on year of transplant. Disclosures: Holmberg: Millenium: Research Funding; Otsuka: Research Funding; Merck: Research Funding; Seattle Genetics: Research Funding; Sanofi: Research Funding

A 4-Drug, Weekly Combination Regimen of Bortezomib, Cyclophosphamide, Liposomal Doxorubicin, and Dexamethasone for Initial Treatment of Multiple Myeloma

Abstract Abstract 5038 Background: Combination regimens have been highly effective in multiple myeloma. Based on our results with the combination of bortezomib, cyclophosphamide, dexamethsone (Bensinger et al Br J Haematol 2010), we added liposomal doxorubicin to assess whether we could improve response as well as evaluate a weekly combination regimen at our academic center and network affiliated sites in the community. The trial is registered as NCT00849251 . Methods: We initially evaluated the regimen in the relapsed setting for toxicity and found it to be well tolerated in 6 patients, then moved to newly diagnosed patients, with the intent that the regimen would serve as induction chemotherapy in preparation for autologous stem cell transplant for transplant-eligible patients. The dosing was bortezomib 1. 6 mg/m2 IV, cyclophosphamide 300 mg/m2 IV, and dexamethasone 40 mg po, days 1, 8, 15, and a single dose of liposomal doxorubicin 30 mg/m2 on day 8 per 28 day cycle. Patients received a maximum of 4 cycles of therapy and the primary endpoints were safety and response at the end of treatment. Results: A total of 31 out of the planned 45 patients (both newly diagnosed and relapsed) were enrolled, as the trial was ended early due to inability to obtain liposomal doxorubicin (Doxil®) for a period of 6 months. One of the relapsed patients was administratively withdrawn after the cycle 1 day 1 treatment. For the remaining 5 relapsed patients who received 2–4 cycles of treatment, the responses were 1 VGPR that was only immunofixation positive, 1 PR and 3 stable disease (SD). For the 24 patients with newly diagnosed MM who completed 1–4 cycles of treatment, there were 2 complete remissions (CRs), 5 VGPRs (2 of which were only immunofixation positive), 11 PRs, and 6 SD for an overall (CR+VGPR+PR) response rate of 75%. Five patients did not complete 4 cycles of therapy, one due to massive pulmonary embolism, one because of need for radiation for intractable back pain during cycle 2 despite marked serological response, and 3 due to stable disease with plateau in response. Of the 25 patients who received BCDD as initial therapy, there have been 3 deaths to date, one due to massive pulmonary embolism on day 13 of the first cycle of treatment, without known history of hypercoagulable risk, one at 7. 7 months of unknown cause, and one at 15. 3 months of progressive disease, resulting in an estimated overall survival of 86% at 2 years from start of therapy. Median follow-up among the 22 survivors is 16. 6 months (range, 8. 1 to 26. 8 months). One patient with a known central line associated deep venous thrombosis in the relapsed group did not exhibit progression of thrombosis off warfarin during therapy. After enrollment of the first 9 patients, an amendment was filed for subsequent patients to receive aspirin prophylaxis, or if at high risk by criteria suggested by Palumbo et al for prophylaxis for MM patients on imids, with low molecular weight heparin or warfarin. Other adverse events that were attributed to investigational regimen include grade 3 hand/foot syndrome (2), infection without neutropenia (1), urinary tract infection (1), and gastrointestinal hemorrhage due to Mallory-Weiss tear (1). Twenty-one patients who completed therapy went on to successful mobilization and collection of peripheral blood stem cells, and autologous or tandem autologous (2) or tandem autologous-minimal myeloablative allogeneic stem cell transplant (7). Two of the 21 patients have died (one at 2. 1 months after first autologous transplant from unknown cause, and one at 9. 8 months from progressive disease). Median follow-up after first autologous transplant among the 19 survivors is 13. 4 months (range, 1. 1 to 20. 4 months). Summary: The 4 drug BCDD regimen exhibited a 75% overall response rate after 4 cycles, with no progression during treatment, was able to be administered weekly in an outpatient setting of both academic and community hematologists and oncologists, and successfully prepared patients for autologous stem cell transplant. Disclosures: Becker: Millennium: Research Funding. Bensinger: Millennium: Research Funding