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VEXAS (Vacuoles, E1 enzyme, X-linked, autoinflammatory and somatic mutation) syndrome is a genetically defined disorder identified in 2020, describing patients with inflammatory syndromes associated with haematological dysfunction. It is a severe, treatment-resistant condition, with estimated mortality between 40% and 63%. A wide range of cutaneous manifestations have been described. Here, we report on two patients with treatment-resistant neutrophilic dermatosis and myelodysplastic syndrome, who were subsequently diagnosed with VEXAS syndrome. Our cases highlight the need for dermatologists' awareness of this novel condition and to initiate early referral to haematologists for appropriate multidisciplinary care.

Although the performance of electronic devices in extreme temperature ranges has been extensively studied, the interconnections, which are still mainly Sn-based materials, require thorough observation and assessment to support the mechanical and electrical stability in subzero to cryogenic temperature environments. An in-depth assessment is required because of the nature of Sn, which has a ductile-to-brittle transition temperature of approximately −60°C. Sn-1Ag-0.5Cu (wt.%) (SAC105) solder joints were subjected to shear testing at room temperature and at −196°C at liquid nitrogen temperature. Isothermal aging at 150°C for 50–500 h prior to cryogenic temperature testing indicated further degradation under certain aging conditions. The study presented here investigates the maximum shear strength variations for SAC105 single solder joints with NiAu and Cu-organic solderability preservative (Cu-OSP) pad surface finishes using a multibond tester with a 10-μm shear height and 100-μm/s shear speed. An increase in the maximum shear strength was observed at liquid nitrogen temperature compared to that at room temperature due to an increase in the yield strength and loss in ductility of the solder material in response to the low-temperature environment. The maximum shear strength decreased with isothermal aging due to the crack propagation path variation. Fracture locations were identified between the Ni pad and the (Cu, Ni)6Sn5 interface for the NiAu surface finish components, and Cu-OSP surface finish solder joints revealed transgranular crack through the Cu6Sn5 and crack propagation between the Cu6Sn5 and the solder interface. The shift in the full fracture location is discussed in association with electron backscatter diffraction (EBSD) analysis on partially sheared solder joints at room temperature and at −196°C.

A 28-year-old Caucasian woman presented with acute kidney injury secondary to cast nephropathy and was diagnosed with Waldenström macroglobulinemia. This was an unusual presentation, as the patient was both young and female. More over renal involvement in Waldenström macroglobulinemia is rare. Histology of this patient revealed the presence of tubular casts and electron microscopic evidence of monoclonal immune deposit disease. Targeted next-generation sequencing of bone marrow revealed a missense mutation in MYD88 (L265 P) along with a nonsense mutation in CXCR4 (S338*) confirming Waldenström macroglobulinemia. After failing to respond to two cycles of bortezomib-based chemoimmunotherapy and a further 2 months of ibrutinib monotherapy, the patient remained dialysis dependent but managed to achieve a partial response with a different chemoimmunotherapy. Following successful stem cell harvesting, she underwent a melphalan-conditioned autologous stem cell transplant to attain a complete remission with hematologic recovery but with persistent renal impairment.

Multiple Myeloma (MM) accounts for 1-2% of all malignancies but is the second most common hematological malignancy. It is characterized by a proliferation of malignant plasma cells. The treatment paradigm of MM in Australia is traditionally hospital-based, complex, and costly. While MM comprises 1-2% of cancer diagnoses, it appears in the top 10 cancer diagnoses requiring hospital admission. The cumulative time spent receiving treatment is a significant burden for patients. The ability to receive treatment at home and maximize time away from hospital-based settings is a key preference for patients receiving anticancer therapies over a prolonged period of time.The Peter MacCallum Cancer Centre and Royal Melbourne Hospital's combined Clinical Hematology Unit has collaborated with their Hospital in the Home departments to develop several innovative programs to address this.We describe our current active programs and potential developments in home-based MM therapy.We have enabled large numbers of patients to receive complex therapies in their own home and the COVID-19 pandemic has increased the pace of the roll out without any compromise in safety. We anticipate that the next raft of immunotherapies will be able to transition into the @Home treatment setting in the coming years.

Treatment outcomes in multiple myeloma (MM) have improved dramatically over the past 10 years. However, patients with high-risk disease such as those with Stage III disease by the Revised International Staging System, the presence of adverse cytogenetics, or who are refractory to proteosome inhibitors, immunomodulatory drugs and monoclonal antibodies may have dismal outcomes. These patients represent an urgent ongoing need in MM. One of the hallmarks of MM is immune dysfunction and a tumour-permissive immune microenvironment. Ameliorating the immune-paresis could lead to improved outcomes. The role of immunotherapies has been growing at an exponential pace with numerous agents under development in clinical trials. In the present review, we provide an overview of immunotherapies in MM, focussing on bispecific antibodies (BsAbs). We review efficacy outcomes from the published clinical trials and consider the important safety aspects of these therapies, in particular the risk of cytokine-release syndrome and immune effector cell-associated neurotoxicity syndrome, and how these compare with patients receiving chimeric antigen receptor T cells. We discuss the MM epitopes being targeted by BsAbs, either in clinical or preclinical stages, and we consider where these therapies might best fit within the future ever-changing paradigm of MM treatment.

Background Traditionally subcutaneous Velcade is delivered in a day ward environment. To reduce hospital visits for our patients, we introduced a Velcade at Home program (VAH) consisting of two arms; self-injection and general practitioner (GP) delivery. Here we present data on the patient experience outcomes. Methods A Self-Injection Assessment Questionnaire was developed for both GP and self-injection arms, adapted from a previously validated tool (1). The questionnaire elicited respondents’ feelings about GP administration or self-injection using a Likert scale format with free text questions used to evaluate time and cost burden. The questionnaire was completed each week during the first cycle in the chemotherapy day unit, prior to cycle 3 (after one full cycle in the community) and at the end of cycle 4. All data were analysed using descriptive statistics. Results The first 20 patients enrolled onto the VAH Program were consented to the study, with 19 completing the program (15 self-injection, 4 GP). In the self-injection arm 46% (7/15) of patients felt anxious prior to their first dose, this decreased to 0/15 by the end of cycle 4. No participants had difficulty removing the cap, depressing the plunger or administering the injection after their first cycle of training. The time reported to complete the injection was shorter for the self-injection arm when compared to their previous injections at hospital (mean 6 minutes and 280 minutes respectively). Similarly, patients in the self-injection arm reported a reduction in the cost burden associated with attending hospital. Of those who responded, 5/7 reported no costs associated with VAH. Conclusion The VAH program has been very well received with patients appreciating the opportunity to regain some control over their treatment and the potential for significant benefit in time and costs. We have been able to share our resources with 7 sites in Australia and New Zealand to help in the implementation of a similar program

Belantamab mafodotin (belamaf) is a BCMA-targeted antibody–drug conjugate recently approved as monotherapy for adults with relapsed/refractory multiple myeloma who have received ≥4 prior therapies. Belamaf binds to BCMA and eliminates myeloma cells by multimodal mechanisms of action. The cytotoxic and potential immunomodulatory properties of belamaf have led to novel combination studies with other anticancer therapies. Here, we describe the rationale and design of DREAMM-5, an ongoing Phase I/II platform study evaluating the safety and efficacy of belamaf combined with novel agents, including GSK3174998 (OX40 agonist), feladilimab (an ICOS; GSK3359609), nirogacestat (a gamma-secretase inhibitor; PF-03084014) and dostarlimab (a PD-1 blocker) versus belamaf monotherapy for patients with relapsed/refractory multiple myeloma.Clinical trial registration: NCT04126200 (ClinicalTrials.gov).

There are currently limited Australian data on the outcomes of autologous stem cell transplantation (ASCT) in elderly multiple myeloma (MM) patients. We present the largest cohort of elderly MM patients aged ≥65 years undergoing ASCT in Australia and report their outcomes based on our two-centre experience. Our study affirms that ASCT is well tolerated, safe and effective in elderly MM patients aged ≥65 years and should be considered an important component of treatment in patients who are fit enough for the procedure.

Introduction Survival following lung transplantation (LTx) is limited by the development of chronic lung allograft dysfunction (CLAD), for which there are few effective therapies and no standardized management. Several small studies have demonstrated the effectiveness of extracorporeal photopheresis (ECP) as a therapeutic option for CLAD. Methods A retrospective descriptive audit of 12 LTx recipients who received rescue ECP for CLAD over 5 years (2013-2018) at the Alfred Hospital, Melbourne, Australia, was completed. Nonresponders to ECP were defined as patients who experienced a 20% decrease in forced expiratory volume (FEV1) within 6 weeks of commencing therapy. Results Mean time since LTx was 849 days and mean time since diagnosis of CLAD was 131 days. Fifty-eight percent of patients were male (n = 7) and 67% responded to ECP therapy (n = 8). Among responders, the mean (95% confidence interval) decline in FEV1 pre-ECP was 9.0 mL/day (5-12 mL/day), compared to 1.4 mL/day (0-4 mL/day) post-ECP (P = .01). Among nonresponders, mean (95% confidence interval) decline in FEV1 was 7.2 mL/day (4-10 mL/day) pre-ECP and 5.0 mL/day (3-7 mL/day) post ECP (P = .2). Nonresponders were more likely to be female (P = .01) and neutropenic (P = .005). Patients with prior exposure to anti-thymocyte globulin had a lowered response to ECP. Conclusion Rescue ECP arrested the decline of lung function in 67% of patients with CLAD. Sex, pre-ECP neutrophil count, and exposure to anti-thymocyte globulin may help determine response to ECP. Future clinical trials are needed to confirm this effect, help predict response to therapy, and ultimately guide the placement of ECP in the treatment algorithm for CLAD.

Introduction/ Background Traditionally, MM harbouring t(11;14) is considered standard risk disease. In the era of novel therapies, however, pts with t(11;14) are reported to have inferior outcomes to other standard risk pts. Evidence of response to the BCL-2 inhibitor, Venetoclax (Ven), has further increased interest in understanding outcomes of t(11;14) pts. In this study, we aimed to describe the historical outcomes of t(11;14) MM and response to Ven in a real-world cohort of Australian pts. Methods This was a retrospective, multicentre study conducted by members of the Australasian Leukaemia and Lymphoma Group, Myeloma Working Party. Cases were identified by interrogation of cytogenetics/FISH database from 2010 to 2019 inclusive. Baseline patient and disease characteristics, treatment exposure and outcomes were extracted from hospital medical records. Descriptive statistics, and survival analyses were performed as appropriate. Results Seventy-four pts [median age 65 years (yrs), range (43-85)] were identified across seven centres. 43% pts had ISS Stage III MM with 88% harbouring additional cytogenetic abnormalities, incl. 13% with gain in 1q and 12% with del(17p). The majority (81%) of pts received proteasome inhibitor (PI)-based 1 st line therapy with 60% having an upfront autologous stem cell transplant (ASCT) and 54% having immunomodulatory drug (IMiD)-based maintenance therapy. Two patients received an allogeneic stem cell transplant after ASCT. The overall response rate (ORR) was 86% with 38% achieving very good partial response (VGPR) or better. The median progression free survival-1 (PFS-1) was 1.91 yrs (95% CI 1.73-2.56) [PI-based, n=60, PFS 1.84yrs (95% CI 1.61-2.41) vs IMiD-based, n=5, PFS 4.58yrs (95% CI 1.16-5.51), HR 0.68 p=0.45] The median overall survival (OS) was 5.35 yrs (95% CI 4.12-6.56). Second and third line therapy was predominantly IMiD-based (see Table 1) with recent introduction of anti-CD38 monoclonal antibodies (mAbs). Median PFS-2 was 0.77 yrs (95% CI 0.39-0.98) while median PFS-3 was 0.65 yrs (95% CI 0.34-1.16). Eleven pts (median 3 prior lines of therapy) were given Ven [Six pts in combination with PI, three with PI and mAbs and two with dexamethasone]. ORR to Ven was 55% with 45% achieving VGPR or better. Median PFS with Ven was 0.54 yrs (85% CI 0.05-2.17). Median PFS for patients with 1-4 lines (n=6) was 1.22 years and median PFS for patients with 5 lines or more (n=5) was 0.54 years, HR 0.56 (95% CI 0.12-2.5). Conclusion For pts harbouring t(11;14), the duration of response to PI-based 1 st line therapy is suboptimal even with the use of ASCT consolidation in the majority of patients. Despite multiple prior lines of therapy, Venetoclax shows promising results and every effort should be made for early identification of this cytogenetic lesion. Further studies are required to examine the impact of novel triplet and quadruplet combination therapy and use of venetoclax early in the disease course of this sub-group of patients. Figure 1 Figure 1. Disclosures Talaulikar: Takeda: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Jansenn: Honoraria, Research Funding; Roche: Honoraria, Research Funding; EUSA Pharma: Honoraria, Research Funding. Gibbs: Janssen, Celgene, Amgen, Takeda, BMS and Pfizer: Consultancy, Honoraria; AbbVie: Consultancy.

Introduction: Single-agent belamaf (GSK2857916), a B-cell maturation antigen-targeting antibody-drug conjugate, induced deep and durable responses in patients with RRMM, with a manageable safety profile with 13 months of follow-up (DREAMM-2; NCT03525678; Lonial et al, ASCO 2020, Poster 436). A platform trial design allows efficient evaluation of belamaf in combination with other anti-myeloma agents, such as a humanized wild-type IgG1 anti-OX40 agonist, an IgG4-inducible T-cell co-stimulator (ICOS) agonist, a gamma-secretase inhibitor, and a humanized programmed cell death (PD)-1 antagonist. The unique, multimodal mechanisms of action (MoAs) of belamaf, in combination with MoAs of these agents, has the potential to achieve synergistic effects in RRMM to further enhance anti-myeloma activity without compromising safety. Methods: DREAMM-5 (NCT04126200) is a Phase I/II study that utilizes a master protocol with separate substudies comprised of sequential dose-exploration (DE) and cohort-expansion (CE) phases, to identify promising, effective belamaf combinations when compared with a shared single-agent belamaf control arm (CE phase only). The DE phase consists of multiple dosing cohorts with belamaf combinations in which patients are assigned to treatment slots by a predetermined algorithmic approach (N≤10 per cohort). A recommended Phase II dose (RP2D) for each combination treatment will be identified based on the safety and preliminary efficacy in the DE phase. At the end of the DE phase, an interim analysis of safety, pharmacokinetic, and efficacy data will also be performed for each substudy treatment combination to determine whether the combination should move forward at the RP2D to the CE phase. Patients in the CE phase (N≥35 per cohort) will be randomized to a substudy and within a substudy to either combination treatment or the belamaf monotherapy control arm; patients will also be stratified by number of prior therapies). Eligible patients will have RRMM and will have received ≥3 prior therapy lines, which includes a prior immunomodulatory agent, proteasome inhibitor, and anti-CD38 antibody; all patients will provide informed consent for participation. The primary objectives of the study are to identify the RP2D (DE phase) and the overall response rate (≥partial response, CE phase), along with safety and tolerability, for each combination treatment. Substudies 1 (combination with GSK3174998, OX40 agonist antibody), 2 (combination with GSK3359609, ICOS agonist antibody), and 3 (combination with nirogacestat [PF-03084014; SpringWorks Therapeutics], gamma-secretase inhibitor) are currently open to enrollment. Substudy 4 (combination with dostarlimab; PD-1 antagonist antibody) is under review. Additional substudies will be explored based on scientific rationale and/or preclinical combination study results. Funding: GSK (Study 208887); belamaf drug linker technology licensed from Seattle Genetics; belamaf monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa; nirogacestat gamma-secretase inhibitor produced by and used in collaboration with SpringWorks Therapeutics. Figure: DREAMM-5 study design Figure 1 Disclosures Richardson: Celgene/BMS, Oncopeptides, Takeda, Karyopharm: Research Funding. Nooka:GlaxoSmithKline: Consultancy, Honoraria, Other: Personal Fees: Travel/accomodations/expenses, Research Funding; Karyopharm Therapeutics, Adaptive technologies: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Spectrum Pharmaceuticals: Consultancy; Adaptive Technologies: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Oncopeptides: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding. Quach:Amgen, sanofi, celgene, Karyopharm, GSK: Research Funding; Amgen, Celgene, karyopharm, GSK, Janssen Cilag, Sanofi.: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline, Karyopharm, Amgen, Celgene, Janssen Cilag: Consultancy; GlaxoSmithKline, Karyopharm, Amgen, Celgene, Janssen Cilag: Honoraria. Trudel:Celgene, Janssen, Takeda, Sanofi, Karyopharm, Amgen Canada: Honoraria; Celgene, Amgen, GSK: Consultancy, Research Funding; GSK, Celgene, Janssen, Amgen, Genentech: Research Funding. Routledge:Celgene, Sandoz: Consultancy; Amgen, BMS, Celgene, Sandoz: Honoraria. Song:Otsuka: Honoraria; Janssen: Honoraria, Research Funding; Amgen, Celgene,Takeda: Consultancy, Honoraria; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Paul:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Khan:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Brouch:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Ferron-Brady:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Yeakey:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Shelton:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Montes de Oca:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Smith:SpringWorks: Current Employment, Current equity holder in publicly-traded company. Im:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Ahlers:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Paul:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Holkova:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Gupta:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company; Novartis: Current equity holder in publicly-traded company. Kremer:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Rodriguez-Otero:GlaxoSmithKline: Consultancy, Current Employment, Current equity holder in publicly-traded company, Honoraria; Kite: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Oncopeptides: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Medscape: Membership on an entity's Board of Directors or advisory committees; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Sanofi: Consultancy, Honoraria.

TPS8055 Background: Len maintenance post ASCT is standard of care for patients (pts) with NDMM. Deep responses (CR or better) post ASCT correlates with better progression free survival (PFS). In a meta-analysis of len maintenance post ASCT (McCarthy PL et al. J Clin Oncol. 2017), only 10.7% of pts achieve CR post ASCT, and 72% of pts who discontinued len maintenance did so because of progressive disease (PD). Selinexor is a selective inhibitor of nuclear export that blocks exportin 1, thus retaining tumour suppressor proteins within the nucleus while blocking proto-oncoprotein translation. It is approved in combination with bortezomib and dexamethasone (dex) for pts with MM who have had at least 1 prior line of treatment, or with dex for pts with penta-refractory MM by the FDA. The oral bioavailability and weekly schedule of selinexor makes it suitable in combination with len for maintenance therapy. Given the encouraging activity (ORR 92%) and tolerability of selinexor, len and dex from the phase 1b/2 STOMP study, we hypothesise that combination low-dose selinexor and len (XR) will be well tolerated and effective, increasing CR and MRD negativity rate post ASCT, thus prolonging PFS compared to len. Methods: ALLG MM23 SeaLAND, is an ongoing randomised, multi-centre, phase 3 trial. Eligible pts ( > 17 years of age) have measurable disease, have undergone 3-6 cycles (C) of induction containing a proteasome inhibitor (PI) and/or immunomodulatory drug and recovered post melphalan-conditioned ASCT with adequate haematopoiesis, renal and liver function, and with ECOG performance status. Registration occurs prior to ASCT with screening between 75 to 115 days post ASCT. The study includes a lead-in safety phase of 20 patients with XR: Len 10mg daily days 1 to 21 and Selinexor 40mg weekly in a 28-day cycle. If well tolerated, Selinexor escalates to 60mg po weekly from C2 and Len to 15mg po daily from C4. Two safety reviews will occur after the 10th and 20th patients completes C2, respectively. Upon meeting safety criteria, a sample size of 290 pts will be randomised 1:1 to XR or lenalidomide (R). Therapy will continue until PD. The primary endpoint is PFS at 3 years post randomisation. Secondary endpoints include ORR and MRD-negativity rate (International Myeloma Working Group Response Criteria), PFS on next treatment line (PFS2), OS, safety and tolerability, quality of life, and cost effectiveness. Main analysis occurs after 232 patients complete 3-years of follow-up. Exploratory objective is to correlate immunological and molecular profiles to treatment response and resistance. ALLG MM23 SeaLAND is a multisite bi-national investigator-initiated trial lead by Australia and New Zealand’s national cooperative group, the Australasian Leukaemia & Lymphoma Group. Clinical trial registration: ACTRN12620000291987p. Clinical trial information: 12620000291987.

The last 5 to 10 years have been marked by considerable advances in both our understanding of the biology and treatment of chronic lymphocytic leukaemia (CLL). Fludarabine-based immuno-chemotherapy is the current standard of care for first line therapy in younger fit patients and although this can be highly effective its use in older co-morbid patients is limited by toxicity, and the prognosis for patients with high risk or fludarabine-refractory disease is poor. The introduction of new antibodies has however, facilitated the use of immuno-chemotherapy in co-morbid patients. Beyond this, the recognition that CLL cells are critically dependent on B-cell receptor (BCR) signalling and interactions with the cellular micro-environment for proliferation and survival has led to the investigation of BCR inhibitors in CLL treatment. These have been shown to be highly effective although a number of questions remain about how they should be optimally used in clinical practice.

Background: MM is a disease of the elderly, with a median age at diagnosis of approximately 65-70 years. Induction chemotherapy followed by high-dose melphalan ASCT is considered the standard of care in younger patients (< 65 years). Historically, transplant eligibility has been determined according to age, based on clinical trials of young MM patients and the potential increased toxicity and mortality in the elderly. However, numerous studies have demonstrated the efficacy and safety in elderly MM patients. Here, we present the largest cohort of elderly MM patients aged ≥ 65 years from Australia and their outcomes based on our multi-centre experience. Methods: A retrospective case note audit identified 426 MM patients who underwent a single ASCT at the Peter MacCallum Cancer Centre and University Hospital Geelong, Australia, between 2008 and 2016. Patients were analysed based on age at ASCT and divided into the "elderly group" (aged ≥ 65 years) and the "younger group" (aged < 65 years). Patient characteristics including ISS stage, cytogenetics, pre and post transplant response, and engraftment duration were collected. Response assessment included overall response rate (ORR), transplant-related mortality (TRM), progression-free survival (PFS) and overall survival (OS). The Kaplan-Meier method was used to estimate OS and PFS and compared using the log-rank test. Results: There were 123 patients in the elderly group (median age 67 years; range 65-79,) and 303 the younger group (median age 56 years; range 31-64). Median follow-up time was 74 months. There were no differences in gender and cytogenetic risk status between the 2 groups. The younger group had a higher proportion of ISS stage 3 disease (25% vs 13%, p=0.031), while the elderly group had a higher proportion of ISS stage 1 disease (53% vs 38%, p=0.024). More patients in the younger group received full dose melphalan conditioning (200mg/m2) compared to the elderly group (89% vs 76%) while the elderly group had a higher percentage receiving a reduced dose between Conclusion: The findings of this retrospective study suggest that ASCT is both well tolerated and effective in MM patients aged ≥ 65 years. Therefore despite the increased availability of novel agents, ASCT should still be an essential element of treatment in elderly MM patients who are fit enough for the procedure. Figure 1. Figure 1. Disclosures Routledge: BMS: Honoraria; Celgene: Honoraria. Harrison:Janssen-Cilag: Other: Scientific advisory board.

Introduction: Chronic graft-versus-host disease (cGVHD) is a major cause of morbidity and non-relapse mortality in allogeneic haematopoietic stem cell transplant patients (Allo-HSCT). Extracorporeal Photopheresis (ECP) is now an established second-line treatment for steroid-refractory cGVHD. Here we report a large, multi-centre case series of 115 patients treated with ECP for cGVHD. To the best of our knowledge, this is the largest reported series of patients receiving fortnightly ECP for cGVHD. Method:A retrospective case note audit identified 115 consecutive Allo-HSCT patients who commenced fortnightly ECP for cGVHD between 2007 and 2016 at The Christie and Central Manchester NHS Foundation Trusts. cGVHD was classified and graded using the National Institutes of Health (NIH) consensus response criteria. Results: Median age when starting ECP was 49 years (range 18-75). 61% patients were male (n=70) and 39% Female (n=45). Underlying disease groups undergoing Allo-HSCT included Acute Leukaemia/Myelodysplastic Syndrome (n=69; 60%), Lymphoma (10%; n=12), Chronic leukaemia (13%; n=15) Myeloma (14%; n=16) and Aplastic Anaemia (3%; n=3). 24% of patients had myeloablative conditioning (n=27) and 76% had reduced-intensity conditioning (n=88). 61% (n=70) received stem cells from Voluntary Unrelated Donors (VUD) and 39% (n=45) Siblings (Sib). Patients received post Allo-HSCT GvHD prophylaxis with Calcineurin inhibitors, either alone, or in combination with Methotrexate and/or Mycophenolate Mofetil. Median time to stopping Calcineurin inhibitor post Allo-HSCT was 12 months (range 0-88). 14 patients received Donor Lymphocyte Infusions (DLI). Median time to development of GvHD post Allo-HSCT was 5 months (range 0-33). 94% developed cutaneous cGVHD (n=108), 32% oral cGVHD (n=37), 23% gut cGVHD(n=27), 24% liver cGVHD (n=28), 11% lung cGVHD (n=13) and 26% ocular cGVHD (n=30). 49% (n=57) patients had sclerodermoid disease. 37% (n=43) had one, 31% (n=36) two, 21% (n=24) three, 9% (n=10) four and 2% (n=2) five organ involvement. All 115 patients had been previously treated with immunosuppressive drugs - 109 Prednisolone; 73 Calcineurin Inhibitors; 60 Mycophenolate mofetil and other (ATG, n=1; Basiliximab, n=1; Methotrexate, n=6; Rituximab, n=10; and Thalidomide, n=18). Median duration of ECP treatment was 12 months (range 1-27 months). Response to ECP was assessed using NIH Criteria - 29% (n=33) Complete Response (CR), 19% (n=22) Partial Response (PR), 16% (n=18) Stable Disease (SD), 11% (n=13) Progressive Disease (PD), 17% (n=19) Death and 9% (n=10) Other. As a result of ECP treatment 26% (n=30) were able to stop steroid treatment while the remaining 74% were able to reduce their steroid dose. There was no overall difference in response between the two centres. Patients with cutaneous and oral cGVHD were more likely to achieve a PR or better (cutaneous p=0.03; oral p=0.05) but there was no difference with other organ involvement. The chance of response was not influenced by the number of organs involved. Median Overall Survival (OS) from the date of Allo-HSCT was 110 months (range 8-221). OS was not influenced by age, donor type, diagnostic group (Acute Leukaemia/Myelodysplastic Syndrome, Lymphoma, Chronic Leukaemia, Myeloma and Aplastic Anaemia), gender or the number and type of organs involved. The only exception was oral cGVHD which was associated with a lower OS (p=0.03). Patients with cGVHD achieving a CR/PR with ECP treatment, had a significantly better OS (40 months vs. median not reached, p Conclusion: ECP is an effective second line treatment for steroid-refractory and steroid-dependent cGVHD with a 50% response rate. This is not affected by the underlying diagnostic group or pattern of organ involvement, however patients with cutaneous and oral cGVHD seem to respond better. As response to ECP translates into better OS, this most likely reflects the reduction in immunosuppressive related complications. Therefore it is worth considering the use ECP treatment early in the management of cGVHD. Disclosures Routledge: Celgene: Honoraria; Jazz Pharmaceuticals: Honoraria; Gilead: Honoraria. Dignan:Jazz: Honoraria; Adienne: Speakers Bureau; Therakos/Mallinckrodt: Honoraria, Research Funding, Speakers Bureau; Gilead: Other: Cl for GvHD Study. Bloor:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Gilead: Honoraria; GSK: Consultancy, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees. Tholouli:Johnson and Johnson: Speakers Bureau; MSD: Speakers Bureau; Celgene: Honoraria; Giles: Speakers Bureau; Amgen: Honoraria, Speakers Bureau.

Introduction: Peg-Asparginase is routinely used in the chemotherapy regimens used for treatment of ALL. Incidence of thrombotic complications is well established in children but there is limited data in adult and young adolescent patients. This is retrospective analysis to assess the risk of thrombotic complications with use of Peg-Asparginase. Methods and Results: 100 patients with Acute Lymphoblastic Leukaemia treated between 2007-2015 who received Peg-Asparginase containing chemotherapy regimen were evaluated for development of thrombotic complications and pancreatitis. There were 69 male patients and 31 female patients. Median age was 29 yr. (range: 16-68 yr). Route of administration for Peg-Asparginase was intravenous in 51 cases and intramuscular in 49 cases. Peg-Aspraginase was administered during induction phase and consolidation cycles according to the relevant chemotherapy protocols. The adverse events included deep vein thrombosis (DVT) in 15 (15%), cerebral venous thrombosis in 7 (7%), Pancreatitis in 2 (2%), DVT and pancreatitis in 1 (1%) and 1 patient had clinically suspected DVT (1%). Complication rate was similar with IV or IM route of administration. 10 patients in IM group (20.4%) and 17 patients in IV group (33.3%) had at least one complication with Peg-Asparginase (P=0.31). Risk of individual complications was similar in both groups (DVT: 14.3% vs. 21.6%, p=0.34; Pancreatitis 2% vs. 3.9%, p=0.57; Cerebral venous thrombosis 4%% vs. 9.8%, p=0.25). There was no difference in the incidence of thrombotic complications with gender, age at diagnosis and use of central venous lines. Conclusions: There is a significant risk of thrombotic events including PE (18% risk of thrombotic events excluding CNS). Risk of CNS events is 7% in this population. Risk appears to be higher with IV administration but this is not statistically significant due to small sample size. Incidence of CNS events is similar to that reported in adolescents participating in UKALL2003 study. The analysis will be extended to evaluate other toxicities especially hepatic toxicity and identify if there are any high risk patients for CNS or thrombotic events including blood counts, clotting, and cytogenetics. Use of LMWH prophylaxis seems reasonable in view of high incidence of thrombotic events even if CNS events are excluded. Disclosures Cavet: Celgene: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau. Somervaille:Novartis Pharmaceuticals Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Introduction: The introduction of novel agentshas revolutionised the treatment of multiple myeloma, with improvements in survival of newly diagnosed and relapsed/refractory patients. However, despite these advances, the role for allogeneic haematopoietic stem cell transplantation (HSCT) in the treatment of these patients remains in question. Reduced-intensity conditioning (RIC) HSCT with Seattle regimen (30 mg/m2 fludarabine and 2 Gray total-body irradiation, TBI) for multiple myeloma has been reported to be an effective treatment with low upfront toxicity, and the potential for graft-versus-myeloma effect (Niederwieser D et al, Blood, 2003). Its use as part of tandem HSCT (autologous HSCT followed by RIC-HSCT) is associated with a treatment-related mortality (TRM) rate as low as 15% (Björkstrand B et al, J Clin Onc, 2011). However, data on survival following auto-HSCT/RIC-HSCT is inconsistent and no unifying consensus has been reached regarding the optimal timing of RIC-HSCT in the treatment algorithm. In this retrospective multi-centre study, we investigated the safety, tolerability and efficacy of RIC-HSCT in multiple myeloma patients in remission following previous auto-HSCT. Methods: A retrospective series was conducted for early-phase, high-risk myeloma patients who underwent RIC-HSCT following prior auto-HSCT in two tertiary transplant centres in Manchester in North West England, between November 2006 and July 2014. Results: Over the eight-year period, 42 myeloma patients (male n=29, female n=13) underwent Seattle-conditioned RIC-HSCT following prior auto-HSCT. 66.6% (n=28) were performed in tandem. Median age at RIC-HSCT was 52 years (range 41-65), and median β2-microglobulin at diagnosis was 3.1 mg/L (range 1.6-18.0). 16 patients had cytogenetics assessed at the time of diagnosis, of which loss of TP53 and translocation of chromosome 14 were most common. 37 patients (88.1%) had previously been exposed to immunomodulatory agents (IMiDs). 53.3% patients (n=24) were in first remission at RIC-HSCT, whilst 37.8% (n=17) were in second remission. 31.1% (n=14) of RIC-HSCTs were performed after second auto-HSCT following previous relapse and re-induction chemotherapy. 34 patients (55.9%) had achieved at least a very good partial response (VGPR) prior to RIC-HSCT. RIC-HSCT was performed a median of 20 months (range 10-89) from diagnosis. Two patients (4.8%) required re-transplantation for failed engraftment, but subsequently engrafted following in vivo T cell-depleting regimens. Mortality at early and interim time-points was low relative to registry and trial series, with TRM of 2.4% (n =1) and 9.5% (n=4) at day 100 and 365, respectively. 37 patients (82.2%) experienced chronic graft-versus-host disease (GVHD). Chronic skin GVHD was observed in 21 patients (grade 1-2: n=20; grade 3-4: n=1); chronic gastrointestinal GVHD in four patients (grade 1-2: n=1; grade 3-4: n=3); chronic hepatic GVHD in six patients (grade 1-2: n=4; grade 3-4: n=2); chronic oral GVHD in 17 patients (grade 1-2: n=17); and chronic ophthalmic GVHD in five patients (grade 1-2: n=5). There was an association between GVHD and enhanced disease control, as complete response rates increased from 26.5% to 51.5% by day 100 post-RIC-HSCT. However, 22 patients (48.9%) eventually relapsed with a median time to relapse of 6.5 months. 13 patients remain in CR one year post-RIC-HSCT. Relapse was treated with escalating donor lymphocyte infusions (DLI, n=13) or IMiDs (n=16). Response to lenalidomide at relapse was potentiated, despite the majority of patients having prior exposure to IMiDs. The median length of follow-up from diagnosis was 27 months (range 1-90). Median overall survival (OS) has not been reached; OS at two years was 69.2% (Figure 1). Conclusions: In this retrospective series we demonstrate the feasibility of Seattle-conditioned RIC-HSCT in multiple myeloma. We observed a very low early TRM of 9.5% and presence of allo-immune disease control (graft-versus-myeloma effect), thereby augmenting IMiD efficacy. Chronic GVHD was prevalent and relapse occurred in a significant proportion of patients, but salvage with DLI and IMiDs highlighted the efficacy of the graft-versus-myeloma effect elicited by RIC-HSCT. Figure 1. Survival outcomes after RIC-HSCT in myeloma. Median OS has not been reached, two-year OS was 69.2%. Figure 1. Survival outcomes after RIC-HSCT in myeloma. Median OS has not been reached, two-year OS was 69.2%. Disclosures Cavet: Celgene: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Celgene: Other: Speaker. Tholouli:Pfizer: Honoraria, Speakers Bureau; MSD: Honoraria, Speakers Bureau; Jazz Pharmaceuticals: Honoraria, Speakers Bureau. Gibbs:Celgene: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees.

Introduction: Immune ThrombocytoPaenia (ITP) in children consists of an isolated thrombocytopaenia (platelet count less than 100 x 109/L) in the absence of any other identifiable cause (Rodeghiero 2009) and is a diagnosis of exclusion. The majority of children diagnosed with ITP remit in the first few months with approximately 30% going on to develop chronic ITP (Thrombocytopaenia persisting > 12 months) (Imbach 2006). The majority of children with chronic ITP are managed supportively and do not require treatment. However, clinically significant bleeding may occur spontaneously or when challenged (e.g. infection, surgery, trauma). For patients who require frequent breakthrough treatment or in whom lifestyle restrictions are unacceptable, the treatment options are limited and the side effects often unacceptable to both families and physicians Initial study reports suggest that thrombopoietin receptor agonists (TPO-RA) are effective and safe in paediatric patients, however longer term follow up data is unavailable Here we present follow-up data on the efficacy and safety on the use of TPO-RA in 34 paediatric patients with Chronic ITP across 5 tertiary referral centres with up to 5 years follow up. Methods: A retrospective case note review was performed for paediatric patients with Chronic ITP who were treated with off-licence TPO-RA in 5 tertiary referral centres. Patients were initially treated on clinical study (PETIT n=25, PETIT2 n=2, or off study n=7). Results: 34 patients (Female n=14, Male n=20) were identified who were treated with TPO-RA between 2009 and 2014. Median age when starting TPO-RA was 10 years of age (Range 2 to 17 years). 70% of patients were White, 12% Asian, 9% Arabic, 6% Hispanic and 3% Mixed ethnicity. Prior to starting TPO-RA all 34 patients had received at least one prior ITP therapy, with 41% receiving ≥3 previous ITP therapies (n=14). 71% had received steroids (n=24), 68% IVIG (n=23), 50% Rituximab (n=17), 27% Anti-D (n=9), 3% steroid sparing agents (n=1) and 3% had undergone splenectomy (n=1). 21% were on concurrent platelet rising therapy when starting TPO-RA (n=7). 97% started on TPO-RA for bleeding and/or thrombocytopaenia (n=33) and 3% started on TPO-RA for surgery (n=1). During this period patients received treatment with Eltrombopag (n=28), Romiplostim (n=5) or both (n=1). Median duration of treatment with Eltrombopag was 30 months (range 6 to 55 months) and Romiplostim was 13 months (range 1 to 32 months). 32 patients were treated for ≥6 months, 28 for ≥1 year, 20 for ≥2 years and 4 for ≥4 years. Median maintenance dose for Eltrombopag was 0.94mg/kg and Romiplostim 7.92micrograms/kg). 53% of patients are still currently taking a TPO-RA (n=18). 1 patient who failed to respond to Eltrombopag, responded to Romiplostim. 50% of patients had a trial off treatment (n=17), with 4 patients remaining off treatment (Eltrombopag n=3, Romiplostim n=1). 4 patients stopped treatment due to the fear of potential side effects, 3 patients stopped treatment due to compliance issues, 4 patients stopped due to a lack of response to treatment and treatment was withdrawn in 1 patient due to subclinical ( Conclusion: Our experience demonstrates that both Eltrombopag and Romiplostim are an effective treatment option in paediatric patients with chronic ITP. Both Eltrombopag and Romiplostim were well tolerated with exposures over 5 and 2 years respectively. 4 patients remain off treatment after a treatment ‘holiday’. Therefore withdrawal of treatment should be considered in all patients who are stable on treatment. No new safety concerns were identified but we would advocate continued surveillance. Disclosures Grainger: Amgen: Honoraria; Baxter: Honoraria, Research Funding; GlaxoSmithKline: Honoraria. Off Label Use: Eltrombopag is a thrombopoietin receptor agonist approved for the treatment of thrombocytopenia in adults with chronic ITP. Use in children and adolescents will be discussed.. Bussel:Shionogi: Membership on an entity's Board of Directors or advisory committees, Research Funding; Rigel: Honoraria; Novartis: Honoraria; Ligand: Membership on an entity's Board of Directors or advisory committees, Research Funding; Immunomedics: Research Funding; IgG of America: Research Funding; GlaxoSmithKline: Equity Ownership, Honoraria, Research Funding; Genzyme: Research Funding; Eisai, Inc.: Research Funding; Cangene: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria; Amgen: Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Symphogen: Membership on an entity's Board of Directors or advisory committees; Sysmex: Research Funding.