Search

Diffuse large B-cell lymphoma with secondary involvement of the central nervous system (SCNS-DLBCL) is a rare condition carrying a poor prognosis. No optimal therapeutic regimen has been identified. We retrospectively analysed 23 patients with SCNS-DLBCL treated with R-IDARAM (rituximab 375 mg/m(2) IV day 1; methotrexate 12·5 mg by intrathecal injection day 1; idarubicin 10 mg/m(2) /day IV days 1 and 2; dexamethasone 100 mg/day IV infusion over 12 h days 1-3; cytosine arabinoside 1000 mg/m(2) /day IV over 1 h days 1 and 2; and methotrexate 2000 mg/m(2) IV over 2 h day 3. Ten out of 23 (44%) patients had CNS involvement at initial presentation ('new disease'), 10/23 (44%) had relapsed disease and 3/23 (13%) had primary refractory disease. 14/23 (61%) of patients responded - 6 (26%) complete response, 8 (35%) partial response. Grade 3-4 haematological toxicity was seen in all cycles, with no grade 3-4 or long-term neurological toxicity. Median follow-up for surviving patients was 49 months. At 2 years, estimated progression-free survival (PFS) was 39% and overall survival (OS) was 52%. Encouraging outcomes were reported in patients with new disease, with 5-year estimated PFS of 50% and OS 75%. R-IDARAM is a well-tolerated regimen with encouraging efficacy in patients with SCNS-DLBCL, although patients with relapsed or refractory disease continue to fare poorly.

Paraproteinaemic neuropathies are a heterogeneous group of disorders most frequently associated with IgM monoclonal gammopathies including Waldenstrom macroglobulinaemia (WM). Their consequences are significant for affected patients, and their management challenging for their physicians. The variability in clinical presentation and time course hamper classification and management. The indications for invasive investigations such as cerebrospinal fluid analysis, nerve conduction tests and sensory nerve biopsies are unclear, and the optimum way to measure clinical response to treatment unknown. When to intervene and and how to treat, also present challenges to physicians. As part of its latest deliberations at the International Workshops on WM (IWWM) in London, UK (August 2014), the IWWM8 panel have proposed a consensus approach to the diagnosis and management of peripheral neuropathies associated with IgM monoclonal gammopathies, including WM. Importantly, a consensus regarding the use of clinical outcome measures and recommended models of care for this group of patients is discussed, as well as appropriate treatment interventions.

Introduction CAD is a rare autoimmune hemolytic anemia with an estimated prevalence of 16 per 1 million. Hemolysis is driven by activation of the classical complement pathway (CP), resulting in erythrocyte opsonization with predominant extravascular destruction and ensuing anemia. Patients with CAD have an increased early mortality and risk of thromboembolism. There are no approved treatments. Sutimlimab (formerly BIVV009) is a first-in-class humanized monoclonal anti-C1s antibody that selectively inhibits the C1 complex of complement, preventing CP activation, while leaving the alternative and lectin pathways intact. The objective of the Cardinal study (NCT03347396) is to assess efficacy and safety of sutimlimab in adults with CAD who have a recent history of transfusion. Methods Cardinal is a pivotal Phase 3, open-label, single-arm, multicenter study of 26 weeks' duration (Part A) with an ongoing extension (Part B). Data is available from Part A. Patients with confirmed diagnosis of CAD were enrolled. Eligibility criteria included baseline hemoglobin (Hb) ≤10 g/dL, total bilirubin level above normal, and ≥1 blood transfusion in the prior 6 months. Sutimlimab was administered intravenously on Days 0 and 7, followed by biweekly infusions. Patients weighing The primary efficacy endpoint was response rate based on a composite of Hb increase ≥2 g/dL or Hb ≥12 g/dL at treatment assessment (average from Weeks 23, 25, and 26) and transfusion avoidance from Weeks 5 to 26. Secondary efficacy endpoints included change from baseline in hemolytic markers (eg, bilirubin) and quality of life (QOL) measured by the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Scale. The proportion of responders for analysis of the primary endpoint was calculated with a 95% exact Clopper-Pearson confidence interval (CI). All secondary endpoints were analyzed using descriptive statistics, frequency, percentage, or CIs. Results Twenty-four patients enrolled and received ≥1 dose of sutimlimab. The mean (standard deviation) age was 71.3 (8.2) years with 62.5% females. Mean (range) baseline Hb was 8.6 (4.9-11.1) g/dL. The median (range) number of transfusions within 6 months prior to enrollment was 2 (1-19) and 62.5% of patients had failed prior therapies. Out of 24 patients, 22 completed Part A; 2 patients were withdrawn early for reasons unrelated to the study drug. The estimated mean (standard error [SE]) Hb increase at treatment assessment time point was 2.6 (0.4) g/dL. Hb improved rapidly after the first dose of sutimlimab with 1.2 g/dL and 2.3 g/dL increases by Weeks 1 and 3, respectively. Mean overall Hb was maintained above 11 g/dL after Week 3 (Figure 1A). Twenty (83.3%) patients had a mean Hb increase ≥1 g/dL. Mean total bilirubin was normalized by Week 3. Seventeen (70.8%) patients remained free of transfusions from Weeks 5 to 26. FACIT-F scores improved within 1 week, peaking by Week 5, and remained stable through Week 26. The estimated mean (SE) FACIT-F score increase at the treatment assessment time point was 10.9 (1.4), consistent with a clinically meaningful response. Hb, bilirubin, and FACIT-F improvements correlated with rapid normalization of complement C4 and near-complete inhibition of CP activity (Figure 1B). The prespecified primary endpoint was met (13 [54.2%] patients). Twenty-two (91.7%) patients experienced ≥1 treatment-emergent adverse event (TEAE), with 7 (29.2%) patients experiencing a serious TEAE (TESAE). There were no TESAEs assessed as related to sutimlimab. There was 1 death in a patient with hepatic cancer that was assessed as unrelated to the study drug. Serious infections were reported, but no meningococcal infections were identified. There were no thromboembolisms and decreases in mean D-dimer and thrombin-antithrombin III complex thrombotic markers were observed. All 22 patients that completed Part A enrolled in Part B. Conclusions The Phase 3 Cardinal study shows that sutimlimab, a first-in-class selective inhibitor of the CP, has a rapid and sustained treatment effect in CAD by preventing hemolysis, significantly increasing Hb, and improving QOL (FACIT-F). These results demonstrate that targeting the CP represents a novel, effective therapeutic approach for the management of CAD and indicate that sutimlimab has the potential to change treatment practices for patients with this condition. Disclosures Röth: Alexion: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; Bioverativ: Consultancy, Honoraria. Barcellini:Novartis: Research Funding, Speakers Bureau; Alexion: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees; Bioverativ: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees. D'Sa:Janssen: Honoraria, Research Funding. Miyakawa:Bioverativ: Consultancy; Sanofi: Consultancy. Broome:Cellphire: Honoraria, Research Funding; Alexion: Honoraria, Research Funding; Bioverativ a Sanofi Company: Honoraria, Research Funding; Incyte: Honoraria, Research Funding; Rigel: Honoraria, Research Funding; Sanofi Genzyme: Honoraria, Research Funding. Michel:Bioverativ: Consultancy; Alexion: Consultancy; Rigel: Consultancy. Kuter:Agios: Consultancy, Honoraria, Research Funding; Alnylam: Consultancy, Honoraria, Research Funding; Argenx: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb (BMS): Consultancy, Honoraria, Research Funding; Caremark: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Actelion (Syntimmune): Consultancy, Honoraria, Research Funding; Up-to-Date: Consultancy, Honoraria, Patents & Royalties: 3 Up-to-Date chapters; Zafgen: Consultancy, Honoraria; Massachusetts General Hospital: Employment; Takeda (Bioverativ): Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Dova: Consultancy, Honoraria; Kyowa-Kirin: Consultancy, Honoraria; Merck Sharp Dohme: Consultancy, Honoraria; Momenta: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Kezar: Research Funding; Platelet Disorder Support Association: Consultancy, Honoraria; Principia: Consultancy, Honoraria, Research Funding; Protalex: Consultancy, Honoraria, Research Funding; Protalix: Consultancy, Honoraria; Rigel: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; Genzyme: Consultancy, Honoraria; Shinogi: Consultancy, Honoraria; Shire: Consultancy, Honoraria; UCB: Consultancy, Honoraria. Jilma:TrueNorth a Bioverativ company, a Sanofi company: Consultancy, Research Funding. Tvedt:Ablynx, alexion and novartis: Consultancy. Lin:Sanofi: Employment. Jiang:Sanofi: Employment. Reuter:Pediatric Infectious Disease Society: Other: Social Media Committee, Vaccine Advocacy Committee; Sanofi: Employment. Hobbs:Sanofi-Genzyme: Employment. Berentsen:Apellis: Consultancy, Honoraria; Alexion: Honoraria; Bioverativ, a Sanofi company: Consultancy, Honoraria; Janssen-Cilag: Honoraria; Mundipharma: Research Funding; True North Therapeutics: Consultancy, Honoraria.

Introduction Arterial and venous events are known to occur in patients with POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, Skin changes) syndrome which may also include myeloproliferation, with a reported rate in the literature of around 20%. This is higher than in the myeloma cohort where the VTE rate from the UK Myeloma XI study was reported as 11.8%. The approach to optimum management of thrombosis in POEMS patients remains undefined. Method The UCLH POEMS Registry is a comprehensive tertiary centre-based UK data repository including patients from 1999 to the present. Data were collated from patients referred in for diagnosis or after treatment and included blood results, neurological and general performance status, previous and active venous thromboembolism (VTE) and arterial events and their management. Results Of the 103 patients in the UCLH POEMS Registry, 20 were excluded due to missing data. Of the 83 patients included, median age was 52 years (31-84) and 54 (65%) were male. Mean haemoglobin at diagnosis was 143 g/L (89-190), platelet count 443 x10^9 (194-741), vascular endothelial growth factor (VEGF) 3536 pg/mL (388-15422), creatinine 75 μmol/L (32-168) and albumin 40 g/L (31-50). Performance status was ≥ 3 in 15 patients. Radiotherapy was used as a treatment modality in 21/83 (25%) and 48/83 (52%) patients received autografts. There were 51 outpatient-based chemotherapy regimens prescribed. Lenalidomide and dexamethasone (LD) was the most common prescription 30/51 (59%), followed by cyclophosphamide and dexamethasone in 10/51 (20%), LD plus cyclophosphamide in 3/51 (6%), melphalan and steroids 3/51 (6%), cyclophosphamide, dexamethasone and thalidomide 2/51 (4%), LD plus ixazomib 1/51 (2%), velcade, thalidomide and dexamethasone 1/51 (2%) and carfilzomib with dexamethasone 1/51 (2%). Of these 51 outpatient-based chemotherapy scripts, 30 received documented thromboprophylaxis (TP). Prophylactic low molecular weight heparin (pLMWH) was prescribed most frequently (17/30) with 16 of these patients receiving an immunomodulatory based chemotherapy regimen. Other TP agents used include: aspirin (6/30), treatment dose LMWH (tLMWH) (2/30), rivaroxaban (2/30), warfarin (2/30) and clopidogrel (1/30). Twenty-five patients experienced a total of 35 clinically apparent arterial or venous events. Seven had more than 1 thrombotic event, 2 of which developed both arterial and venous thromboses. Three patients had a prior history of VTE;1 with historic DVT developed pulmonary emboli, and 2 had arterial events after historic VTE. Eleven patients had 14 VTEs including DVT (6/14), PE (4/14) and 4 PICC-associated DVT occurring during melphalan-based autograft. Most VTEs occurred during active disease with median VEGF 2731 (444-5000). Five venous events occurred on chemotherapy, including 4 during a melphalan-based autograft, and 1 on LD. VTE occurred despite prophylactic LMWH in 3 patients (2 unknown). Treatment comprised LMWH (4), warfarin (4), or the direct oral anticoagulants, rivaroxaban (1) and apixaban (1). One patient did not receive treatment for a PICC-associated DVT. Sixteen patients experienced 21 arterial events including stroke (7/21), peripheral vascular disease (6/21), MI (4/21) and microvascular disease (2/21). Most events occurred during active disease with median VEGF 3155 (637-10640). Three occurred on anti-POEMS therapy: one patient (VEGF 4555) developed a second stroke on LD and LMWH prophylaxis; one patient on LD (VEGF 10640) and prophylactic rivaroxaban 10mg developed PVD, and another on melphalan and prednisolone (VEGF 2000-4000) and warfarin for atrial fibrillation (target INR 2.0-3.0) developed PVD. Conclusion The venous and arterial event rate in this cohort at 35/83 (42%) is over double that previously reported. There were more arterial events than venous, and most occurred in a state of active disease and off anti-POEMS therapy (26/35), suggesting that treatment-related risk factors are less of a driver for thrombosis than the disease itself. There was no discernible relationship with thrombocytosis. Thromboprophylaxis is commonly used in POEMS patients receiving outpatient-based chemotherapy with the most common agent being prophylactic LMWH. With the high incidence of arterial events in the presence of active disease, the role for anti-platelet agents or indeed DOACs remains undefined in this patient group. Disclosures Thomas: Sanofi: Membership on an entity's Board of Directors or advisory committees. D'Sa:Janssen: Honoraria, Research Funding.

Introduction Waldenström's macroglobulinaemia (WM), an indolent IgM-secreting non-Hodgkin's B-cell lymphoplasmacytic lymphoma, has a reported average age of diagnosis of 65-70 years. and it is often regarded as a disease of the elderly. However, a significant proportion of patients are diagnosed at a younger age and data about this cohort is relatively limited, partly because of the low disease incidence. We seek to further elucidate the characteristics and impact of the disease in the younger patient cohort. Methods The WMUK Rory Morrison Registry (RMR) was searched for all patients younger than 60 years on day of diagnosis. Demographics, disease characteristics, treatment information and survival status were collected retrospectively. Results of patient reported outcome measures (PROMs) were collated. Results 269 patients from 16 UK centres were identified, with years of diagnosis between 1978 and 2018. Analysis focused on 235 patients who fulfilled diagnostic criteria for WM. Patient characteristics are shown in table 1. M:F ratio was 1.61:1 of which 158 patients were Caucasian, 17 Asian, 5 Black, 3 mixed and 6 of other ethnicity, 56 unrecorded. Bone marrow results were available in 156 patients from time of diagnosis, with a median infiltration of 40%. MYD88 L265P was found in 61/74 patients (82.4%) and CXCR4 mutation in 14/39 patients (35.9%). Median Hb was 114/L (range 33-170), platelet count 250x109/L (range 24-689), IgM 19 (range 0-65) and B2-microglobulin 2.7mcg/mL (range 0.5-56.3). The baseline IPSSWM scores were available for 115 patients. 9 patients were anti-MAG antibody positive and 11 had cryoglobulins. Treatment was received by 164 patients (69.8%). The median time from diagnosis to treatment was 2.5 months, range 0-312 months; 69 patients had one line, 32 two lines, 31 three lines, 12 four lines, and 20 five or more lines.14% received R-CHOP as first line therapy, 12.2% DRC,12.2% R-Bendamustine, 7.3% Rituximab monotherapy, 6.7% R-CVP and 6.7% chlorambucil. However, since 2010 DRC and R-Bendamustine were the most frequent. Following first line treatment, 14.7% achieved CR, 55.3% PR or VGPR, 11.9% MR and 14% had SD or PD. At some point in their disease course, high-grade transformation (HGT) was noted in 2 patients and CNS involvement in 10. 30 patients had undergone autologous and six patients allogenic transplantation. Complete, up to date survival information was available for 188 patients, of who 40 patients were deceased (median time from diagnosis 116 months, range 14-451 months). Unfortunately, cause of death was available for only 8 patients at time of analysis, including disease-related in 4, sepsis in 2, HGT in 1 and subdural haemorrhage in 1. One-, 5- and 10-year overall survival (OS) rates were 99.5%, 90% and 81.1%. There was a significant difference in OS according to IPSSWM risk (log rank, P Of 164 patients asked about their level of disease understanding on a scale of 0-10, the median rating was 0 (average rating 1.85). Only eight patients rated it as 10. Functional information was available for 62 patients, of who 42 (67.7%) had impairment in their ability to go for a walk outside, eight patients (12.9%) required assistance with self-care and one patient (1.6%) was fully dependent on others for personal care. 32 patients (51.6%) needed to spend some or most of their day in a bed or chair. 29 patients (47.8%) had suffered significant financial difficulties because of their diagnosis. Of 59 patients who responded about psychological wellbeing, 36 patients (61%) described feeling depressed. One patient described feeling 'very' depressed, 8 patients 'moderately' depressed and 27 patients 'slightly' depressed. Conclusion A significant proportion of patients with WM are diagnosed under the age of 60 years, and despite its limitations, this retrospective analysis of a large cohort of younger patients illustrates the evolving treatment landscape in the UK. To be expected, WM significant impacts on quality of life and psychological and financial wellbeing in a cohort who would expect to be in work. Encouragingly, OS rates are generally good, although a high IPSSWM risk carries a markedly lower 5-year OS rate also in the younger cohort. A more detailed analysis is underway to explore these issues further. Disclosures McCarthy: Janssen: Honoraria, Other: Educational grant to attend meetings . Pratt:Binding Site, Amgen, Takeda, Janssen, Gilead: Consultancy, Honoraria, Other: Travel support. D'Sa:Janssen: Honoraria, Research Funding.

Background Waldenström's macroglobulinaemia (WM) is a rare non-Hodgkin B cell lymphoma. Given its rarity, information about both patient demographics and disease characteristics are limited. Treatment is indicated for symptomatic patients and treatment regimens have evolved significantly in recent years. The Rory Morrison Registry (RMR) has comprehensive patient data available for analysis. We seek to draw conclusions about UK patient demographics and disease characteristics, and evaluate how treatment practices have evolved. Methods The RMR was searched for all patients with a diagnosis of WM. Patient demographics, disease characteristic, pathology results, treatment information and survival status retrieved. Kaplan Meier and log rank analysis was performed. Results 671 patients were identified from 19 different UK centres. Median age at diagnosis was 64 years (range 27-92, figure 1). Year of diagnosis ranged from 1978 to 2019, with 7 patients diagnosed Median haemoglobin at diagnosis was 112g/L (range 33-170), platelet count 242 (3-806), B2M 3 (range 0.2-56.3) and M-protein 17g/L (range 0-110.5). Median bone marrow infiltration was 40% (range 0-100%), with 35% lymphocytes and 5% plasma cell. MYD88 L265P mutations were detected in 160/190 patients (84.2%). CXCR4 mutations, for which testing is not widely available, were detected in 20/76 patients (26.3%). Peripheral neuropathy was seen in 74 patients, with 28 anti-MAG antibody positive. Other manifestations at diagnosis included cryoglobulinaemia (26), amyloidosis (12) and Schnitzler's syndrome (7). 2/317 patients were HIV positive, 4/341 HCV antibody positive, 27/334 HBSAb positive, and 12/327 HBCAb positive. IPSSWM score at diagnosis was available for 352 patients, with a low score in 122 (34.7%), intermediate score in 103 (29.3%), and high score in 123 (45%). 440 patients (65.6%) had received treatment, with a median time from diagnosis to treatment of two months (range 0-312). Indications for first line treatment initiation were: 35% paraprotein-related, 30% lymphoma-related , 2.1% B-symptoms, and a combination of indications for the remainder. Hyperviscosity was the treatment indication in 24.8% of patients, fatigue in 21.6% and peripheral neuropathy in 9.8%. At treatment commencement, 47% of patients had a haemoglobin of Lines of therapy received was one in 43.6%, two in 24.1%, three in 4.8%, four in 6.6% and ≥5 in 10.9%. In the past decade, 27.8% received DRC, 16.4% R-Bendamustine, 8.9% rituximab monotherapy, 7.7% R-CHOP and the rest varying combinations. 2.2% had received Bortezomib-containing therapy. Before 2010, chlorambucil (21.8%), R-CHOP (10.9%) and FC (9.3%) were the most frequently used first line treatments. BTK-inhibitors have become the most commonly used second line therapy, representing 23% of second line therapy after 2010, reflecting the availability of Ibrutinib on the Cancer Drugs Fund from 2017 and the availability of BTKi trials since 2015. 88 patients had received a BTKi at some point. 118 patients had deceased. Only 30 patients had a cause of death available; this included 7 patients who died from WM itself, 6 from pneumonia, 5 from sepsis (2 were neutropaenic), 3 from HGT, 2 from haemorrhage, 2 from thrombotic events, and 1 from CNS relapse. 5- and 10-year OS rates from diagnosis were 90.5% and 79.4%, with a significant difference in OS rates according to IPSSWM risk at diagnosis (p Conclusions The median age at diagnosis was 64 years, with a third of patients diagnosed under the age of 60. Although diverse, the most frequent indications for treatment in this cohort are hyperviscosity, fatigue and peripheral neuropathy. OS rates are high and correlate with IPSSWM risk, but a majority of patients had received multiple lines of therapy reflecting the chronically relapsing nature of WM. Treatment practices are clearly evolving, with increasing first line use of DRC and R-Bendamustine, as well as BTK inhibitors for relapsed disease. Disclosures McCarthy: Janssen: Honoraria, Other: Educational grant to attend meetings . Pratt:Binding Site, Amgen, Takeda, Janssen, Gilead: Consultancy, Honoraria, Other: Travel support. D'Sa:Janssen: Honoraria, Research Funding.

A 51-year-old right-handed man developed a sensory neuropathy with the sensation of walking on pebbles, and tight cramping pains in the calves requiring amitriptyline. Two months later, he became unsteady with difficulty walking downstairs necessitating a stick, with associated fatigue and weight loss of half a stone. He had a history of haemophilia type A and liver cirrhosis from hepatitis C, contracted through the transfusion of blood products in the 1980s. On examination, there was evidence of a distal symmetrical sensorimotor polyneuropathy with Medical Research Council (MRC) power grade 4+/5 in the intrinsic hand muscles and 0/5 in ankle plantar and dorsiflexion. Supinator, knee and ankle deep tendon reflexes were all absent, with mute plantar responses. He had a loss of pinprick sensation to the knees, vibration loss to the costal margins and temperature perception was altered to the mid-thighs. There was dusky pigmentation of the skin and peripheral oedema in the lower limbs. His history and examination findings are typical of a distal symmetrical neuropathy (see box 1 for the differential diagnosis of a painful large fibre neuropathy). Serological workup for a neuropathy should include full blood count, B12, folate, erythrocyte sedimentation rate (ESR), glucose, thyroid function, a serum protein electrophoresis and immunofixation, and possibly an antinuclear antibody. Note that it is typical for hospital laboratories only to perform serum immunofixation if the serum protein electrophoresis is abnormal. The greater sensitivity of immunofixation may find low-level paraproteins that would be otherwise undetectable, and which may be highly relevant in the context of neuropathy. He also has a history of hepatitis C which is associated with cryoglobulinaemia and cryoglobulinaemic peripheral nerve vasculitis, and therefore an important differential. Constitutional symptoms, including weight loss, are uncommon in isolated peripheral neuropathy, and therefore systemic causes should be considered, including vasculitis, malignancies, metabolic (diabetes), …

Bendamustine is a unique bifunctional alkylating agent with promising activity in myeloma. Despite the increasing number of studies demonstrating its efficacy in both the upfront and relapse settings, including patients with renal insufficiency, the optimal use of bendamustine, in terms of dosage, schedule and combination with other agents, has yet to be defined. It is currently licensed for use as frontline treatment with prednisolone for patients with myeloma who are unsuitable for transplantation and who are contraindicated for thalidomide and bortezomib. Studies in relapsed/refractory patients are currently ongoing with other combinations. Given the increasing data to date, the UK Myeloma Forum believes that bendamustine with steroids alone or in combination with a novel agent could be considered for patients with multiply relapsed myeloma. This document provides guidance for the use of bendamustine for patients with myeloma until the results of definitive studies are available.

Objectives Bortezomib is an effective antimyeloma therapy, but clinical benefits can be limited by neurotoxicity. In newly diagnosed, older patients, modification of the biweekly dosing schedule to weekly regimens improves tolerability whilst maintaining efficacy. There is less information on the efficacy and tolerability of weekly bortezomib regimens in the relapsed/refractory setting. Here, we report our experience of weekly intravenous bortezomib in clinical practice in relapsed/refractory patients. Methods We analysed fifty-two patients who received weekly bortezomib for relapsed/refractory MM. Results Thirty-one per cent of patients received bortezomib beyond first relapse. Almost all (94%) also received steroids and 48% also received an alkylator. The median cumulative dose was 22.6 mg/m2, and median length of treatment was 164 d. Three patients reported grade 2 sensory neuropathy, and one reported grade 3 motor neuropathy. There were no grade 4 neurotoxicities. Eighty-three per cent achieved a PR or greater, and the median PFS for the whole group was 13 months. One-year PFS and OS were 53% (95% CI 39–66.6%) and 78% (95% CI 66.7–89.6%), respectively. Conclusions Weekly intravenous bortezomib when used in combination with steroids ± alkylator is effective in relapsed/refractory MM, producing outcomes comparable with biweekly regimens and with lower rates of peripheral neuropathy.

Myeloma patients who become refractory to immunomodulatory agents (IMiDs) and bortezomib have poor survival, with limited therapeutic options. Pomalidomide has shown improved survival and good tolerability in this patient cohort in clinical trials, but real world data are scarce. We retrospectively analysed all patients treated with pomalidomide at five UK centres between 2013 and 2016. Of 85 patients identified, 70 had sufficient information for response assessments. Median age was 66 years [40-89], 96·5% were refractory to IMiDs, 72·9% were refractory to both an IMiD and bortezomib and 92·9% were refractory to their last treatment. Of 45 patients with fluorescence in situ hybridization results 64% had adverse risk, 19 patients (22·4%) had an estimated glomerular filtration rate

Background Multiple myeloma osteolytic disease affecting the spine results in vertebral compression fractures. These are painful, result in kyphosis, and impact respiratory function and quality of life. We explore the impact of time to presentation on the efficacy of spinal treatment modalities. Methods We retrospectively reviewed 183 patients with spinal myeloma presenting to our service over a 2 year period. Results Median time from multiple myeloma diagnosis to presentation at our centre was 195 days. Eighty-four patients (45.9 %) were treated with balloon kyphoplasty and the remainder with a thoracolumbar-sacral orthosis as per our published protocol. Patients presenting earlier than 195 days from diagnosis had significant improvements in patient reported outcome measures: EuroQol 5-Dimensions (p

International audience; Bing Neel syndrome is a rare disease manifestation of Waldenström’s macroglobulinemia that results from infiltration of the central nervous system by malignant lymphoplasmacytic cells. In this guideline we describe the clinical symptoms, as well as the appropriate laboratory and radiological studies, that can aid in the diagnosis. The presentation of Bing Neel syndrome may be very diverse, and includes headaches, cognitive deficits, paresis, and psychiatric symptoms. The syndrome can present in patients with known Waldenström’s macroglobulinemia, even in the absence of systemic progression, but also in previously undiagnosed patients. Diagnostic work-up should include cerebral spinal fluid analysis with multiparameter flow cytometry to establish B-cell clonality, protein electrophoresis and immunofixation for the detection and classification of a monoclonal protein as well as molecular diagnostic testing for immunoglobulin gene rearrangement and mutated MYD88. MRI of the brain and spinal cord is also essential. The second challenge is to expand our knowledge of prognosis and treatment outcome. Prospective clinical trials on Bing Neel syndrome patients that employ uniform treatment along with appropriate laboratory cerebral spinal fluid assessments and standardized MRI protocols will be invaluable, constituting a significant step forward in delineating treatment outcome for this intriguing disease manifestation.

The use of consolidation or maintenance to improve disease response, and hence clinical outcome, following autologous stem cell transplantation (ASCT) remains the subject of intense clinical research. We carried out a single-arm study to assess the toxicity and efficacy of a short block of consolidation therapy with cyclophosphamide, low dose thalidomide and dexamethasone (CTD) in patients within 6 months following ASCT, as part of frontline therapy for symptomatic multiple myeloma. Forty-five patients who had not progressed were enrolled on the study, and 43 completed treatment on protocol. This regimen was well tolerated soon after ASCT, with only grade 1/2 toxicity apart from neutropenia, and no long-term sequelae. Importantly, CTD consolidation improved the depth of response in treated patients, increasing the complete/very good partial response rate from 44% at 3 months, to 72% at 12 months, which was significantly higher compared with a historical group of control patients (P = 0·002). There was a trend to longer progression-free survival that favoured the study group. Consolidation therapy did not adversely affect subsequent disease response to salvage therapies at relapse. We conclude that CTD consolidation may be a useful, non-toxic and cost-effective strategy to deepen disease response following ASCT, and deserves further study in a randomized trial.

653. Spencer, A., Prince, H.M., Roberts, A.W., Prosser, I.W., Bradstock, K.F., Coyle, L., Gill, D.S., Horvath, N., Reynolds, J. & Kennedy, N. (2009) Consolidation therapy with low-dose thalido- mide and prednisolone prolongs the survival of multiple myeloma patients undergoing a single autologous stem-cell transplantation procedure. Journal of Clinical Oncology, 27, 1788–1793. Srkalovic, G., Cameron, M.G., Rybicki, L., Deitcher, S.R., Kattke-Marchant, K. & Hussein, M.A. (2004) Monoclonal gammopathy of undeter- mined significance and multiple myeloma are associated with an increased incidence of venothromboembolic disease. Cancer, 101, 558– 666. Stadtmauer, E.A., Weber, D.M., Niesvizky, R., Belch, A., Prince, M.H., San Miguel, J.F., Facon, T., Olesnyckyj, M., Yu, Z., Zeldis, J.B., Knight, R.D. Guideline 74 a 2011 Blackwell Publishing Ltd, British Journal of Haematology, 154, 32–75 & Dimopoulos, M.A. (2009) Lenalidomide in combination with dexamethasone at first relapse in comparison with its use as later salvage therapy in relapsed or refractory multiple myeloma. European Journal of Haematology, 82, 426–432. Stewart, A.K., Vescio, R., Schiller, G., Ballester, O., Noga, S., Rugo, H., Freytes, C., Stadtmauer, E., Tarantolo, S., Sahebi, F., Stiff, P., Meharchard, J., Schlossman, R., Brown, R., Tully, H., Benyunes, M., Jacobs, C., Berenson, R., White, M., DiPersio, J., Anderson, K.C. & Berenson, J. (2001) Purging of autologous peripheral-blood stem cells using CD34 selection does not improve overall or progression-free survival after high-dose chemo- therapy for multiple myeloma: results of a multicenter randomized controlled trial. Journal of Clinical Oncology, 19, 3771–3779. Stewart, A.K., Chen, C.I., Howson-Jan, K., White, D., Roy, J., Kovacs, M.J., Shustik, C., Sadura, A., Shepherd, L., Ding, K., Meyer, R.M. & Belch, A.R. (2004) Results of a multicenter randomized phase II trial of thalidomide and prednisone mainte- nance therapy for multiple myeloma after autol- ogous stem cell transplant. Clinical Cancer Research, 10, 8170–8176. Stewart, A.K., Bergsagel, P.L., Greipp, P.R., Dis- penzieri, A., Gertz, M.A., Hayman, S.R., Kumar, S., Lacy, M.Q., Lust, J.A., Russell, S.J., Witzig, T.E., Zeldenrust, S.R., Dingli, D., Reeder, C.B., Roy, V., Kyle, R.A., Rajkumar, S.V. & Fonseca, R. (2007) A practical guide to defining high-risk myeloma for clinical trials, patient counseling and choice of therapy. Leukemia, 21, 529–534. Terpos, E. & Dimopoulos, M.A. (2005) Myeloma bone disease: pathophysiology and management. Annals of Oncology, 16, 1223–1231. Terpos, E. & Rahemtulla, A. (2004) Bisphosphonate treatment for multiple myeloma. Drugs of today (Barcelona, Spain: 1998), 40, 29–40. Terpos, E., Sezer, O., Croucher, P.I., Garcia-Sanz, R., Boccadoro, M., San Miguel, J., Ashcroft, J., Blade, J., Cavo, M., Delforge, M., Dimopoulos, M.A., Facon, T., Macro, M., Waage, A. & Son- neveld, P. (2009) The use of bisphosphonates in multiple myeloma: recommendations of an ex- pert panel on behalf of the European Myeloma Network. Annals of Oncology, 20, 1303–1317. Tosi, P., Zamagni, E., Cellini, C., Cangini, D., Tac- chetti, P., Tura, S., Baccarani, M. & Cavo, M. (2004) Thalidomide alone or in combination with dexamethasone in patients with advanced, relapsed or refractory multiple myeloma and renal failure. European Journal of Haematology, 73, 98–103. Tosi, P., Zamagni, E., Cellini, C., Plasmati, R., Cangini, D., Tacchetti, P., Perrone, G., Pastorelli, F., Tura, S., Baccarani, M. & Cavo, M. (2005) Neurological toxicity of long-term (>1 yr) thalidomide therapy in patients with multiple myeloma. European Journal of Haematology, 74, 212–216. Vela-Ojeda, J., Garcia-Ruiz-Esparza, M.A., Padilla- Gonzalez, Y., Gomez-Almaguer, D., Gutierrez- Aguirre, C.H., Gomez-Rangel, D., Morales- Toquero, A., Ruiz-Delgado, G.J., Delgado-Lamas, J.L. & Ruiz-Arguelles, G.J. (2007) Autologous peripheral blood stem cell transplantation in multiple myeloma using oral versus I.V. melphalan. Annals of Hematology, 86, 277–282. van de Velde, H.J., Liu, X., Chen, G., Cakana, A., Deraedt, W. & Bayssas, M. (2007) Complete response correlates with long-term survival and progression-free survival in high-dose therapy in multiple myeloma. Haematologica, 92, 1399–1406. Vigneau, C., Ardiet, C., Bret, M., Laville, M., Fiere, D., Tranchand, B. & Fouque, D. (2002) Inter- mediate-dose (25 mg/m) IV melphalan for multiple myeloma with renal failure. Journal of Nephrology, 15, 684–689. Vogel, C.L., Yanagihara, R.H., Wood, A.J., Schnell, F.M., Henderson, C., Kaplan, B.H., Purdy, M.H., Orlowski, R., Decker, J.L., Lacerna, L. & Hohneker, J.A. (2004) Safety and pain palliation of zoledronic acid in patients with breast cancer, prostate cancer, or multiple myeloma who previously received bisphosphonate therapy. Oncologist, 9, 687–695. Waage, A., Gimsing, P., Juliusson, G., Turesson, I., Gulbrandsen, N., Eriksson, T., Hjorth, M., Niel- sen, J.L., Lenhoff, S., Westin, J. & Wisloff, F. (2004) Early response predicts thalidomide efficiency in patients with advanced multiple myeloma. British Journal of Haematology, 125, 149–155. Wang, M., Knight, R., Dimopoulos, M., Siegel, D., Rajkumar, S.V., Facon, T., Alexanian, R., Yu, Z., Zeldis, J., Olesnyckyj, M. & Weber, D. (2006) Lenalidomide in combination with dexametha- sone was more effective than dexamethasone in patients who have received prior thalidomide for relapsed or refractory multiple myeloma. Blood (ASH Annual Meeting Abstracts), 108, Abstract 3553. Weber, D.M., Gavino, M., Delasalle, K., Rankin, K., Giralt, S. & Alexanian, R. (1999) Thalidomide alone or with dexamethasone for multiple mye- loma. Blood, 94(Suppl. I), 604a. Weber, D., Wang, M., Chen, C., Belch, A., Stadt- mauer, E.A., Niesvisky, R., Yu, Z., Olesnyckyj, M., Zeldis, J., Knight, R.D. & Dimopoulos, M. (2006) Lenalidomide Plus High-Dose Dexamethasone Provides Improved Overall Survival Compared to High-Dose Dexamethasone Alone for Relapsed or Refractory Multiple Myeloma (MM): Results of 2 Phase III Studies (MM-009, MM-010) and Subgroup Analysis of Patients with Impaired Renal Function. Blood (ASH Annual Meeting Abstracts), 108, 3547. Weber, D.M., Chen, C., Niesvizky, R., Wang, M., Belch, A., Stadtmauer, E.A., Siegel, D., Borrello, I., Rajkumar, S.V., Chanan-Khan, A.A., Lonial, S., Yu, Z., Patin, J., Olesnyckyj, M., Zeldis, J.B. & Knight, R.D. (2007) Lenalidomide plus dexa- methasone for relapsed multiple myeloma in North America. New England Journal of Medicine, 357, 2133–2142. Wechalekar, A., Amato, D., Chen, C., Stewart K., A. & Reece, D. (2005) IgD multiple myeloma–a clinical profile and outcome with chemotherapy and autologous stem cell transplantation. Annals of Hematology, 84, 115–117. Wijermans, P., Schaafsma, M., Norden, Y.v., Ammerlaan, R., Wittebol, S., Sinnige, H., Zweegman, S., Kooi, M.v.M., Griend, R.V.d., Lokhorst, H. & Sonneveld, P. (2008) Melphalan/ prednisone versus melphalan/prednisone/thalid- omide in induction therapy for multiple myelo- ma in elderly patients: final analysis of the dutch cooperative group HOVON 49 study. Blood (ASH Annual Meeting Abstracts), 112, Abstract 649. Zervas, K., Mihou, D., Katodritou, E., Pouli, A., Mitsouli, C.H., Anagnostopoulos, A., Delibasi, S., Kyrtsonis, M.C., Anagnostopoulos, N., Terpos, E., Zikos, P., Maniatis, A. & Dimopoulos, M.A. (2007) VAD-doxil versus VAD-doxil plus tha- lidomide as initial treatment for multiple mye- loma: results of a multicenter randomized trial of the Greek Myeloma Study Group. Annals of Oncology, 18, 1369–1375. Zucchelli, P., Pasquali, S., Cagnoli, L. & Ferrari, G. (1988) Controlled plasma exchange trial in acute renal failure due to multiple myeloma. Kidney International, 33, 1175–1180. Guideline a 2011 Blackwell Publishing Ltd, British Journal of Haematology, 154, 32–75 75

Supportive care plays an increasingly important role in the modern management of multiple myeloma. While modern treatments have significantly prolonged overall and progression free survival through improved disease control, the vast majority of patients remain incurable, and live with the burden of the disease itself and the cumulative side effects of treatments. Maintenance of quality of life presents challenges at all stages of the disease from diagnosis through the multiple phases of active treatment to the end of life. Written on behalf of the British Committee for Standards in Haematology (BCSH) and the UK Myeloma Forum (UKMF), these evidence based guidelines summarize the current national consensus for supportive and symptomatic care in multiple myeloma in the following areas; pain management, peripheral neuropathy, skeletal complications, infection, anaemia, haemostasis and thrombosis, sedation, fatigue, nausea, vomiting, anorexia, constipation, diarrhoea, mucositis, bisphosphonate-induced osteonecrosis of the jaw, complementary therapies, holistic needs assessment and end of life care. Although most aspects of supportive care can be supervised by haematology teams primarily responsible for patients with multiple myeloma, multidisciplinary collaboration involving specialists in palliative medicine, pain management, radiotherapy and surgical specialities is essential, and guidance is provided for appropriate interdisciplinary referral. These guidelines should be read in conjunction with the BCSH/UKMF Guidelines for the Diagnosis and Management of Multiple Myeloma 2011.

Introduction: The optimal management of relapsed/refractory lymphoma is a significant clinical challenge. Early phase clinical trials are primarily designed to assess safety but also represent options for patients with limited therapeutic choices. Outcomes for lymphoma patients on early phase trials have previously been reported as single centre cohorts or grouped analyses with other malignancies. We performed a novel meta-analysis of publically available reports of early phase trials in lymphoma and compared the outcomes with those from our early phase trials unit. Methods: The outcomes of lymphoma patients enrolled on early phase trials at a UK tertiary centre were reviewed. AEs were graded according to CTCAE v4.0 and response criteria evaluated per protocol. Patient and therapy characteristics, AEs and best clinical responses were summarised by descriptive statistics. Individual-patient survival data were analysed using Kaplan-Meier method and survival curves compared with the log-rank test. A systematic literature review was performed using EMBASE, MEDLINE and clinicaltrials.gov to identify publicly available reports of early phase clinical trials reported in 2016-2017 and data was extracted by two independent reviewers. Meta-analyses of ORRs were performed using random-effect models. Results: 50 patients were enrolled onto 9 Phase I and I/II trials between March 2012 and June 2018, Four patients participated in 2 trials, considered separate events. 5 IMPs were small molecular inhibitors, 4 immunotherapies, 4 first in human and 8 investigated as monotherapy. Diagnoses included 42 aggressive NHL (aNHL) [30 DLBCL, 3 PMBCL, 3 Richters, 1 MCL, 5 T cell], 10 indolent NHL (5 WM, 2 FL, 2 MZL, 1 CLL/SLL) and 2 HL. Median age was 54 yr (27-83), 72% male, with a median time from diagnosis of 22.5 months and median 3 prior lines of therapy (range 1-8). Patients received a median number of 2 cycles of IMP (range 1-28) over 57.5 days (IQR: 37-116). 42.6% experienced grade 3-4 toxicity and 31.5% required dose interruptions of >7 days. ORR and clinical benefit rate (≥SD) were 28% and 47% respectively (CR 4%, PR 24%, SD 19%). Patients were followed up for a median of 11.4 months. Median PFS and OS were 2.3 and 6.8 months respectively, with PFS and OS at 3, 6 and 12 months being 45.8%, 34.4%, 26.5% and 58.4%, 45.4% and 38.8%. Median OS was greater for those who received 164 lymphoma trial reports were included in the meta-analysis detailing outcomes of 4537 patients (Table 2). All studies were Phase I (72.6%) or I/II and 78% included only patients with lymphoma (all other trials included reported subgroup analysis of lymphoma patients). 95.7% of trials evaluated a single IMP, 52.4% used combinations of agents. IMPs most frequently investigated were small molecule inhibitors (25.6%), antibody-drug conjugates (11.6%) and epigenetic modifiers (10.4%). Immunotherapy trials comprise 36.1% of studies, including ADCs, checkpoint inhibitors (7.32%), naked antibodies (9.2%) and cellular therapies including CAR-T (7.93%). The ORR of all patients was 54.2% (95% CI 49.6% - 58.8%). Subset analysis showed that cellular therapies studies reported a pooled ORR of 62.5% (50.9 - 72.8) and antibody therapies 58.3 (46.7 - 69.2). Conclusion: The outcomes of lymphoma patients on early phase trials is historically perceived as very poor, partly due to the grouping of analysis with other malignancies. Our cohort had an ORR of 28% and OS at 6 months of 58.4%. The meta-analysis of global studies reporting lymphoma specific outcomes, revealed an ORR of 54.2%. This included all histological subtypes and some previously untreated patients. Our cohort was enriched for relapsed aNHL, which may account for the inferior ORR in our cohort. Together, both data sets indicate improved outcomes compared to historical reports and support enrolment of suitable patients into phase I trials when conventional options are exhausted. Disclosures Ardeshna: Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Takeda: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding. Popat:Amgen: Honoraria. Townsend:Gilead: Consultancy, Honoraria; Roche: Consultancy, Honoraria.

Peripheral T-cell lymphomas (PTCLs) are rare and heterogeneous haematological malignancies that can rarely develop first in the peripheral nervous system, or more commonly, invade nerves from more usual primary locations. Patients with PTCLs usually respond poorly to treatment and have a poor clinical outcome.We report a patient with multiple skin lesions, multifocal mononeuropathies and constitutional symptoms all suggestive of a lymphoproliferative disorder, in whom repeat skin biopsies and clonality studies failed to achieve a diagnosis. Neurophysiological studies confirmed severe post-ganglionic lesions in the lower limbs including the sciatic, femoral, obturator, tibial and sural territories. Based on this neurotropic presentation we undertook a sural nerve biopsy, despite the clinical and neurophysiological presence of a nerve lesion more proximal to the biopsy site, and this allowed us to establish a final diagnosis of PTCL. The patient was treated successfully with chemotherapy and an autologous stem cell transplant.In our case PET imaging and MR neurography provided radiological evidence of widespread lesions in the subcutaneous and nerve tissues, and there is emerging evidence for the importance of PET imaging in the diagnostic work-up of PTCLs. Furthermore, a post-treatment PET scan confirmed the complete metabolic remission, highlighting its usefulness as a surveillance tool.

Neurological complications of haematological malignancies are wide ranging but isolated myopathy as a presenting complaint is rare.Cases: 63 year-old lady with progressive proximal upper then lower limb weakness over 7 years to wheelchair-dependence and hoist-transfers. Muscle biopsy revealed nemalin rods, HIV negative, IgG kappa paraprotein=6 g/L. Late-onset nemalin rod myopathy was diagnosed; function is stable 6/12 post-autologous bone marrow transplant.56 year-old lady with limb-girdle weakness leading to immobility over 2 years and IgG lambda MGUS. Re-examination of muscle biopsy revealed amyloid deposition, SAP scan negative for systemic AL amyloid. Treated with velcade and dexamethasone but died from amyloid cardiomyopathy 6/12 later.73 year-old man with painless deltoid weakness. Muscle biopsy revealed plasma cells infiltrate and lightchain deposition with matched lightchain restriction in bone marrow, IgG kappa paraprotein=8 g/L. Cyclosporin and dexamethasone were recommended for infiltrative multifocal, myopathic plasmacytoma.28 year-old female with pain, fatigue and pelvic-girdle weakness was diagnosed with haemophagocytic lymphohistiocytosis without systemic lymphoma or connective tissue disease. Muscle biopsy demonstrated T-cell and macrophage infiltration. Muscle symptoms are responding to steroids, mycophenolate, cyclosporine and etopiside. An allogenic bone marrow transplant is planned.We describe four cases of progressive myopathic weakness as the primary manifestation of an underlying haematological disorder.

Avon Haematology Unit, Bristol Haematology and Oncology Centre, Bristol, Department of Haematology, St Helier Hospital, Carshalton, Surrey, UK, Department of Haematology, Sahlgrenska University Hospital, Gothenburg, Sweden, Department of Medicine, Malmo University Hospital, Malmo, Sweden, Division of Immunity and Infection, University of Birmingham, Birmingham, Department of Clinical Biochemistry, Frenchay Hospital, Bristol, Department Haematology, University College, London, Glasgow Western Infirmary, Glasgow, UK, Department of Haematology, NTNU/St Olavs Hospital, Trondheim, Department of Haematology, Ulleval University Hospital, Oslo, Norway, Department of Haematology Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark, and Myeloma UK.

The paraprotein is an immunoglobulin produced at abnormally high levels by a clone of plasma cells. These plasma cells may be relatively benign, with minimal proliferation and no associated tissue damage or cause organ impairment via cytokine effects or through the paraprotein itself. Myeloma is usually a disease of the elderly, typically presenting non-specifically with anaemia, back pain, renal impairment, hypercalcaemia or recurrent infections, or inducing medical emergencies such as acute renal failure, overwhelming sepsis, spinal cord compression and hyperviscosity. Prompt diagnosis requires a low threshold for screening investigations. Evidence of myeloma-related organ and tissue impairment should be actively sought. Treatment is tailored to the patient, in recognition of the increased co-morbidities present in this population. Supportive care is exceptionally important. This is accompanied by combination chemotherapy, aiming to reduce disease burden and reverse organ damage where possible. Other rarer conditions may be associated with a paraprotein, such as Waldenstrom's macroglobulinaemia, solitary plasmacytomas, light chain (AL) amyloidosis and lymphoproliferative disorders. They require specialist investigation and management.

The optimal salvage treatment for patients with chronic lymphocytic leukemia (CLL) who have failed or relapsed shortly after treatment with purine-analogue based treatment remains undefined. This i...

Summary In2001,referencetotheuseofimagingintheBritishCommittee for Standards in Haematology guidelines for the diagnosis and management of myeloma was confined to the standard use of plain X-rays in the diagnostic skeletal survey and emergency use of computed tomography (CT) and magnetic resonance (MR) imaginginthesettingofcordcompression.Sincethen,therehas been a steady rise in interest in the use of various imaging techniques in the management of myeloma. The purpose of imaginginthemanagementofmyelomaincludestheassessment of the extent and severity of the disease at presentation, the identification and characterisation of complications, and the assessment of response to therapy. Plain radiography, CT, and MRimagingaregenerallyestablishedexaminationtechniquesin myeloma whilst positron emission tomography (PET) and 99 Technetium sestamibi (MIBI) imaging are promising newer scanning techniques under current evaluation. These standalone imaging guidelines discuss recommendations for the use of each modality of imaging at diagnosis and in the follow up of patients with myeloma.

Bing-Neel syndrome (BNS) is a rare complication seen in patients with Waldenström macroglobulinaemia (WM), in which lymphoplasmacytic lymphoma (LPL) cells colonize the central nervous system (CNS). In this retrospective multi-centre study, we present the clinicopathological features, imaging findings, therapy, response and outcomes of 34 patients with BNS. The median time from WM diagnosis to BNS diagnosis was 3 years, 15% of patients were diagnosed with BNS at the time of WM diagnosis, and 22% of patients developed BNS when responding to active treatment for WM. Patients with BNS presented with variable clinical features including limb motor deficits, change in mental status and cranial nerve palsies. The diagnosis was made using a combination of cerebrospinal fluid cytology, flow cytometry and detection of the MYD88 L265 mutation, and magnetic resonance imaging. The estimated 3-year overall survival rate was 59%. Of the survivors, 40% have evidence of pathological or radiological persistence of disease. Age older than 65 years, platelet count lower than 100 x 109/l, and treatment for WM prior to BNS diagnosis were associated with worse outcome. Exposure to rituximab for treatment of BNS was associated with a better outcome. Multi-institutional collaboration is warranted to improve treatment and outcomes in patients with BNS.

The feasibility and efficacy of a triple regimen of oral weekly cyclophosphamide, monthly pulsed dexamethasone and low-dose Thalidomide (CDT) was studied in 52 patients with relapsed or refractory multiple myeloma (MM). All 52 patients were evaluable for response with a median follow up of 18 (4-29) months. About 17% achieved complete response (CR), 62% partial response (PR), 11% minimal response (MR), 6% stable disease (SD) and 4% progressive disease (PD), resulting in an objective response rate (>= MR) of 90%. Subsequent to successful response, nine patients received high-dose therapy (HDT) followed by stem cell transplantation (SCT) and 34 received thalidomide monotherapy as maintenance. Response rate was not influenced by disease status, prior HDT or age. The regimen was successfully delivered to all patients except for one patient who developed abnormal liver function at 7 weeks. Infective complications were minimal and there were no infection-related deaths. The estimated overall and event-free survival (EFS) at 2 years was 73% and 34%, respectively, and the median time to progression has not been reached. We conclude that the CDT regimen is safe, well tolerated and effective in patients with relapsed and refractory myeloma.

Myeloma remains incurable with a median survival of 4 years, but outcome can be improved by the use of high-dose therapy. We used the etoposide, methylprednisolone, cytarabine and cisplatin (ESHAP) regimen as second-line therapy in 42 newly diagnosed myeloma patients who had failed vincristine, adriamycin and dexamethasone (VAD)- type therapy (n = 36), responded to first-line treatment but persisted in having significant residual marrow plasmacytosis (n = 5) or failed prior stem cell harvesting (n = 1), with the dual aim of improving disease response and mobilizing peripheral blood stem cells. Fourteen of 21 (67%) patients with no change or progressive disease after VAD responded to ESHAP; seven of 12 (58%) patients with minor response converted to partial response. Marrow plasmacytosis fell from a median of 52% at diagnosis to 23.5% after primary therapy and to15% after ESHAP. ESHAP chemotherapy was well-tolerated. There were 11 admissions due to febrile neutropenia (n = 7), nausea and vomiting (n = 2), pneumonia (n = 1) and perforated bowel (n = 1). Renal function deteriorated in 13 of 42 patients after ESHAP, but none required renal support. ESHAP mobilization was performed in 32 patients of whom 87% achieved a CD34(+) yield >2 x 10(6)/kg. In all, 38 patients proceeded to high-dose therapy. The overall survival for all patients was 62% at 4 years following ESHAP. We conclude that ESHAP has acceptable toxicity and efficient stem cell mobilizing capability, effectively cytoreduced this chemoresistant group of patients, and did not appear to adversely affect transplant outcome.

T-cell receptor (TCR) BV spectratyping provides information concerning immune reconstitution complementary to that derived from monoclonal antibody analysis of surface antigen expression. However, the most appropriate way to analyse and represent these data, the number of subfamilies that should be analysed, and the effects of CD4/8 ratio on observed diversity, remain unclear. A diversity scoring system was developed based on analysis of 11 cord blood (CB) and 12 normal adult BV spectratypes. CB subfamily spectratypes demonstrated minor deviations from a Gaussian pattern consistent with current knowledge about germline TCR rearrangements. Diversity scores were significantly lower in myeloma patients than normal adults (P < 0.001) and fell significantly following stem cell transplantation (P = 0.003). Subsequently increasing diversity was not detected by two previously described complexity scoring systems. The CD4/8 ratio was neither the major determinant of the absolute diversity score nor of the change in score for individual patients, suggesting that analysis of unselected mononuclear cells can provide information largely independent of CD4/8 ratios. There was a relatively low correlation between individual subfamily scores and overall diversity score. The novel and objective diversity scoring system described appears better able to document changes in spectratype patterns than previously described techniques and should aid the standardization of reporting.

Background: Cold agglutinin disease is an autoimmune hemolytic anemia with limited treatment options and no established standard of care. The pathophysiology is driven by the classical complement pathway in which IgM auto-antibodies bind erythrocytes and fix complement via initial binding and activation of the C1 complex generating active C1s protease. Anemia results from extravascular hemolysis of complement opsonized erythrocytes, primarily in the liver. The anti-C1s antibody BIVV009 inhibits C1s activity, and specifically blocks the classical complement pathway, leaving the alternate and lectin complement pathways intact. We hypothesized that classical complement pathway blockade using BIVV009 would prevent hemolysis, correct anemia, and obviate the need for transfusions in patients with primary cold agglutinin disease. Methods: Six patients primary cold agglutinin disease patients were enrolled in an open label Ph1/1b trial. The study was conducted in three parts: Part A, single ascending doses in healthy volunteers (HV); Part B, multiple ascending doses in HV; and Part C, multiple doses in patients with four classical complement mediated diseases including cold agglutinin disease. Patients in Part C received a test dose of 10 mg/kg BIVV009, followed by a full dose of 60 mg/kg 1-4 days later, and three additional weekly doses of 60 mg/kg. Biweekly fixed doses of 5.5g were used for maintenance therapy in a subsequent Named Patient Program. Results: All infusions were well tolerated without need for pre-medication, and pharmacokinetic data demonstrated that BIVV009 infusions supported biweekly treatment. BIVV009 concentrations >18µg/mL inhibited the classical pathway of complement activation (as assessed by the Wieslab-CP assay). BIVV009 infusion subsequently raised endogenous C4 levels 3.2-fold (95%CI: 2.4-4.0 fold; p3.5 g/dL (mean 4.3g/dl; 95%CI: 3.8-4.9 g/dL; individual best response; p Conclusion: BIVV009 was well tolerated and immediately stopped hemolysis in 6 of 6 severely anemic patients suffering from primary cold agglutinin disease, increasing hemoglobin by a mean of 4.3g/dl and precluding the need for transfusions while on BIVV009. Based on these encouraging results, BIVV009 received FDA Breakthrough Therapy designation and pivotal trials will be initiated to further define BIVV009 safety and efficacy profiles. Figure 1: individual hemoglobin response patterns in primary cold agglutinin disease patients during the initial exposure of 6 weeks Figure 1 Figure 1. Disclosures Jaeger: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses. D'Sa: Janssen Cilag: Consultancy, Honoraria, Other: Education grant, Research Funding; Amgen: Consultancy, Honoraria, Research Funding. Patou: Inc., a Bioverativ Inc. Company: Employment. Panicker: Bioverativ, Inc.: Employment, Equity Ownership. Parry: Bioverativ Therapeutics Inc.: Employment. Gilbert: TrueNorth Therapeutics Inc., a Bioverativ Inc. Company: Other: formerly Employment. Jilma: Biomed: Research Funding; Recardio: Research Funding; Emcools: Research Funding; Bayer: Research Funding; Themis: Research Funding; Syntheract: Research Funding; Bioverativ: Research Funding; TrueNorth Therapeutics: Research Funding; JHL: Research Funding; Baxalta: Research Funding; Arsanis: Research Funding; VitaerisBios: Research Funding; TrueNorth Therapeutics Inc.: Consultancy; Valneva: Research Funding; Prediction Biosciences: Research Funding; Boehringer Ingelheim: Research Funding; Octapharma: Research Funding.

We describe a previously healthy 53 year old woman with a progressive multifocal neurological syndrome. She developed gradually progressive patchy numbness and horizontal diplopia over 3 years, night sweats and 15 kg weight loss over 1 year, and weakness of the face and four limbs over 9 months. Previous treatment for her symptoms included dual anti-platelet agents then warfarin for a positive lupus anticoagulant, oral fludarabine (50 mg for 5 days) following a diagnosis of mild chronic lymphocytic leukaemia (CLL) on bone marrow biopsy, and two courses of oral steroids (25 mg/day prednisolone; 20 mg/day dexamethosone each tapered over 4 weeks). Neurological symptoms progressed despite these treatments. On examination she mobilised with a frame. There were partial right III, VI and bilateral VII cranial nerve palsies. There was wasting of intrinsic hand muscles, distal lower limb muscles and right deltoid. There was asymmetric proximal and distal weakness in all limbs ranging from no active contraction of right deltoid, flicker of contraction of left hamstrings to mild weakness of ankle dorsiflexors. There was patchy loss of reflexes and flexor plantars. She had sensory loss to light touch and pinprick in multiple dermatomes. The working diagnosis was CLL-associated immunemediated radiculopathies and cranial neuropathies. She was treated with rituximab 375 mg/m and hydrocortisone 100 mg weekly for 8 weeks without additional steroids (repeated previous steroid-associated central serous retinopathy). She made a near complete response. Three months after the rituximab her only residual symptom was with feeling a little unsteady. The only abnormalities on neurological examination were slight diplopia on right gaze and reduced vibration sensation to the ankles. Investigations (Table 1) had dramatically improved. She was maintained on oral cyclophosphamide 50 mg/day, however, had a minor relapse after 5 months and received a repeat rituximab course with good effect. She is neurologically stable on maintenance rituximab 375 mg/m every 3 months. Mechanisms by which CLL could be associated with neurological symptoms include direct leukaemic infiltration, indirectly through immune-mediated effects, opportunistic infection related, treatment related or chance association. Neurological syndromes are found in 11% of CLL patients mostly relating to opportunistic infections [1]. Cases of CLL associated with GBS [2, 3], MillerFisher syndrome [4], subacute IDP [5], mononeuritis multiplex [5] and polyneuropathy [5] are reported. A case with multiple radiculopathies and cranial neuropathies was reported recently [6], however, direct leukemic infiltration of nerve roots was evident on imaging and CSF. In our patient repeated MRI and CSF examinations showed no evidence of direct leukaemic infiltration. J. M. Morrow (&) M. P. Lunn M. M. Reilly MRC Centre for Neuromuscular Diseases, Department of Molecular Neurosciences, UCL Institute of Neurology, National Hospital for Neurology and Neurosurgery, Box 102, WC1N 3BG London, UK e-mail: j.morrow@ion.ucl.ac.uk

BEAM-conditioned autologous SCT improves the quality of response in Waldenstrom’s macroglobulinaemia and lymphoplasmacytic lymphoma: a single centre’s 10-year experience

e288 (Mel) a further ASCT seems reasonable. Querying effectivity and efficiency to overcome therapy-induced exhausted bone marrow function in a heavily pre-treated population, we assessed the outcomes of 61 pts. receiving a 3rd Mel-based salvage ASCT (ASCT3) after tandem ASCT as part of 1st line therapy, querying the databases of six German MM centres. 61 pts. with a median age of 63 years at ASCT3 (range, 38-77) were identified. In 5 of 50 available analyses, cytogenetics could be classified high-risk (17p13 del, t(4;14), t(14;16), amp1q21, del1p). At a median nr. of 3 lines of pre-treatment (range, 1-10) 45 pts. had either received bortezomib and/or lenalidomide, and 37 pts. both. 11 pts. had been double refractory and 23 pts. at least had been refractory to one novel agent prior to ASCT3. With a median Mel dose of 100mg/m2 and 3.1x10E6 CD34 cells/kg all pts. achieved stable engraftment despite a median graft age of 52 mos. (range, 1-154). A remarkable improvement of platelet count and haemoglobin (62.3% /49.2% of all pts.) within 3 mos. of ASCT3 could be obtained. Overall response rate ( PR) was 59% with a median PFS of 9 mos. and a median OS of 26 mos. for the entire group, respectively. 3rd salvage ASCT at late relapse is not only effective with an ORR of 59% and associated with a 9 mos.’ PFS interval but also contributes to improved haematopoiesis. Thus, pts. may tolerate further lines of therapy what is suggested by an OS of 26 mos. In addition, ASCT offers a substantial treatment-free interval when compared to either novel drug. Unfavourable cytogenetics were associated with worse PFS of 2 mos. but not median OS (8 mos.), meanwhile being double refractory was linked with an inferior OS compared to non-refractory pts. (8 vs. 23 mos.). However, benefit seems to depend on PFS after initial ASCT ( 18 mos. ->5 mos.’ PFS after ASCT3, 19-36 mos. ->18 mos., >36 mos. ->23 mos.). Figure 1 A) Progression-free survival and B) overall survival of all patients PO-359 Outcome of Pomalidomide Therapy in Relapsed /Refractory Myeloma: A Uk Multi-Centre Experience N. Maciocia, F. Sharpley, E. Belsham, H. Renshaw, S. Schey, S. Cheesman, A. Cerner, A. Rismani, S. D’sa, M. Streetly, B. Reuben, M. Jenner, K. Ramasamy, K. Yong, N. Rabin Haematology, University College London Hospitals NHS Foundation Trust, London; Haematology, Oxford University Hospitals NHS Trust, Oxford; Haematology, University Hospital Southampton NHS Foundation Trust, Southampton; Haematology, King’s College Hospital NHS Foundation Trust, London; Haematology, Guy’s and St Thomas’ NHS Foundation Trust, London Background: Pomalidomide is licensed in Europe for patients with relapsed/refractory myeloma, who have received at least two prior therapies (lenalidomide/bortezomib) plus progressed on their last therapy. In the phase 3 NIMBUS study, pomalidomide/dexamethasone (POMA-DEX) was associated with longer PFS (4.0 v 1.9 months) and OS (12.7 v 8.1 months) compared to dexamethasone alone (San Miguel et al 2013). Aims: To assess the real-world clinical efficacy of POMA-DEX in several large UK centres. Methods: Patients had measurable disease (IMWG criteria) and received at 15th International Myeloma Workshop, September 23-26, 2015 least 1 cycle of POMA-DEX. Response was assessed and high risk disease defined as per IMWG. PFS and OS were estimated using Kaplan-Meier method. Results: 79 patients were identified and 62 (78.5%) included in response analyses. All patients received pomalidomide (2-4mg D1-21) /dexamethasone, 30/79 (38%) received another agent(s) [clarithromycin (23), cyclophosphamide (9), carfilzomib (1), bortezomib (1)]. Median age was 67yrs (range 40-89). Median time from diagnosis was 4.9yrs (range 0.5 to 18); median prior therapy lines was 4 (range 1-8). Prior therapies were lenalidomide (100%), bortezomib (98%), thalidomide (84%), ASCT (61%). 73 patients (92%) were refractory to their last therapy, and 58 (73%) were double refractory (bortezomib/IMiDs). Median FU was 6.4 months (0.92-34.5). Median no of cycles was 4 (range 1-32), and median dose 4 mg. In those with starting GFR /1⁄4 SD was achieved in 58/62 (94%). Median PFS was 4.3 months and OS 13.7 months (Figure 1A+B). Reduced GFR (

Introduction and epidemiology Solitary plasmacytoma, which accounts for less than 5% of plasma cell dyscrasias is characterized by a localized proliferation of malignant plasma cells in the absence of evident disease elsewhere. Such a proliferation may arise in a bone (solitary bone plasmacytoma or SBP) or an extra-medullary compartment (extramedullary plasmacytoma or EMP). Plasmacytomas may also arise in a multifocal manner without evidence of malignant plasma cells in the intervening tissues. Extra-medullary plasmacytomas may also arise in the context of multiple myeloma. Solitary Bone Plasmacytoma SBP may arise at any age, but the median age of onset at 55 years is 10 years younger than that for myeloma, with a 1.87:1 male to female ratio[1]. Clinical and laboratory features In two-thirds of cases, SBP arises in the axial skeleton, including the spine (thoracic > lumbar > sacral > cervical spine), skull, ribs and sternum and, in one-third, the appendicular skeleton, including the shoulder girdle, pelvic girdle or the extremities [2]. Localized skeletal pain due to the solitary osteolytic lesion is a typical presentation of SBP. If the spine is affected, spinal cord or nerve root compression may be an important clinical consequence. Other presentations include pathological fracture of the affected bone, a soft tissue mass due to extra-medullary extension of the tumor and in a small proportion, symptoms of peripheral neuropathy.

Background Exercise programmes are beneficial for cancer patients however evidence is limited in patients with multiple myeloma (MM), a cancer that is characterised by osteolytic bone disease, giving rise to high levels of bone morbidity including fractures and bone pain. Methods We conducted a single arm phase 2 study of an exercise programme (EP) as rehabilitation for treated MM patients, to evaluate feasibility, effects on QOL and physiological parameters. Patients were given individualised programmes, comprising stretching, aerobic and resistance exercises, carried out under supervision for 3 months then at home for a further 3 months. Results Study uptake was high, 60 of 75 (80%) patients approached consented to the study. Screen failures (11, due to fracture risk and disease relapse) and patient withdrawals (12) resulted in a final 37 patients enrolling on the programme. These 37 patients demonstrated high attendance rates in the supervised classes (87%), and high levels of adherence in home exercising (73%). Patients reported better QOL following the EP, with improvement in FACT-G and Fatigue scores over time from baseline (p Conclusions An EP in MM patients is feasible and safe, with high attendance and adherence. Benefits in QOL, fatigue and muscle strength await confirmation in randomized studies, prompting urgent evaluation of the benefits of EP in the rehabilitation of MM patients.

About 5 per cent of the overall UK cancer burden can be attributed to occupational exposures. However, occupational physicians in clinical practice are most likely to be called upon to support and advise employed patients with non-occupational cancers. Support services in the UK are being reconfigured to help the growing population of cancer survivors to live full and active lives for extended periods. Returning to the workplace is a part of this goal, and occupational physicians are likely to see increasing numbers of adults seeking still to work after treatment for conditions that in the past would have led to ill health-related retirement. Set against these improvements in clinical outcome, and the increasing emphasis on support for patients who achieve long-term survival, is evidence that many working-age adults treated for the common cancers subsequently encounter financial and occupational difficulties. People with cancer often experience a loss in income as a result of their condition. Thus, although most working adults diagnosed with primary cancer return to work, a significant minority do not. Cancer is increasingly seen as an illness that can be effectively treated, but functional outcomes vary considerably. Cancer survivorship is considered to encompass people who are undergoing primary treatment, in remission following treatment, show no symptoms of the disease following treatment, or are living with active or advanced cancer. Occupational physicians may be requested to assess work capability and provide advice on workplace support for cancer survivors in any of the survivorship states. In the UK, 98 per cent of public sector and 30 per cent of private sector employers have access to occupational health services. Employers will normally seek guidance from these services on how to manage employees who have developed a serious illness such as cancer. This means that occupational physicians can be in a key position to coordinate the vocational rehabilitation of cancer survivors. This chapter offers an overview of the evidence on work capability, rehabilitation, and occupational risk assessment that may apply to adults diagnosed with a range of cancers.

Background. Survival for older patients with multiple myeloma (MM) has improved with novel agents such as Proteasome inhibitors (PIs) and Immunomodulatory drugs (IMiDs) . Outcomes in this heterogeneous population are also affected by pre-morbid fitness, comorbidities and tolerance of therapy. We analysed the outcomes of first line systemic therapy in this older patient group, aiming to explore the influence of patient, disease and regimen factors on outcomes. Methods. Non-transplant eligible patients undergoing first line therapy between April 2008 and April 2016 were identified retrospectively from electronic prescribing records; patient and disease features, toxicity and dose modifications were obtained from clinical records. FISH was performed on CD138+ cells using standard probes, and adverse risk was defined as per IMWG criteria. Survival was estimated using Kaplan-Meier methods and disease response by IMWG criteria. Cox Regression (univariate and multivariate) analysis was performed to identify factors influencing progression free (PFS) and overall survival (OS). Results. 84 patients were identified with median age 76 years (range 52-97); 24(28.6%) had cardiac and 12(14.3%) had pulmonary comorbidities. There was an equal spread of ISS stage and 26(31.0%) patients had extramedullary disease (EMD). Of 44 patients with FISH results at diagnosis, 18 (40.9%) had high risk features including 9(20.5%) with del(17p). Patients received a range of treatments; 51(60.7%) had PI-based regimens mainly with Bortezomib, 18(21.4%) received IMiDs (13 Thalidomide, 5 Lenalidomide) and 13(15.5%) chemotherapy. The median total duration of therapy including maintenance was 7.7months (range 0.7-24.1); this was longer (9.6months) in patients receiving IMiDs. The median PFS was 13.1 months (95% CI 10.6-15.5) and median OS was 40.5months (95% CI 30.3-50.7). The overall response rate (ORR) was 70.2%, and was higher in patients treated with novel agents (IMiD 72.2%, PI 72.0%) compared to patients treated with chemotherapy (61.6%). Younger age (70-80years vs. ≥80years), ISS stage 1, disease response ≥PR, maintenance therapy and longer total duration of therapy were associated with longer PFS in univariate analysis, and EMD was associated with shorter PFS(p's Looking at factors predicting OS on univariate analysis, ISS stage 1, IMiD therapy, maintenance therapy and longer duration of therapy were associated with prolonged OS (p's 18 (21.7%) patients discontinued therapy early due to toxicity; this was more frequent with PI (23.5%) and chemotherapy regimens (20.5%) compared to IMiD regimens (16.7%). 48(57%) patients required dose alterations due to toxicity, and this was commoner with IMiD (72%) compared to chemotherapy (38%) or PI (55%) based regimens. Conclusion. We report a sequential cohort of non-transplant eligible patients undergoing first line therapy in the era of novel agents. Our results indicate a consistent benefit for PFS and OS with longer duration of therapy, independent of response, regimen or adverse risk disease. ISS 1 was also an independent predictor of prolonged PFS and OS. Treatment regimen type and response did not correlate independently with PFS or OS. Despite the presence of comorbidities and discontinuations for toxicity, the PFS and OS outcomes are encouraging. This review of real-world outcomes highlights the potential benefit of continuous therapy in older patients. Improved ways of identifying patients susceptible to toxicity and use of frailty-adjusted treatment schedules would further improve outcomes in this patient group. Disclosures Yong: Autolus Ltd: Equity Ownership, Patents & Royalties: APRIL based chimeric antigen receptor; Janssen: Research Funding.

Introduction. The outlook for myeloma patients who relapse after or become refractory to bortezomib and IMiDs is poor, with limited therapeutic options and a median survival (OS) of 9 months. In the phase 3 MM-003 study, pomalidomide plus low-dose dexamethasone resulted in a significant PFS (median 4 vs 1.9 months) and OS (median 13.1 vs 8.1 months) benefit, compared to high-dose dexamethasone. Information on real-world outcomes of pomalidomide therapy is limited. We carried out a retrospective analysis of patients receiving pomalidomide in the UK, to compare outcomes and tolerability with published clinical trial data, and focus on high risk subgroups. Methods. All patients treated with pomalidomide at 5 major UK centres between August 2013 and March 2016 were identified from chemotherapy records, and clinical data including toxicity and survival from patient records. Disease response and adverse FISH were defined as per IMWG. Survival was estimated using Kaplan-Meier, and correlations made using log-rank methods. Key subgroups: eGFR Results. A total of 85 patients were identified. Of these, 70 (82%) had measurable disease (IMWG criteria) and received ≥1 cycle so were included in response analyses. Baseline patient characteristics are reported in Table 1. 96.5% of patients were refractory to one or more IMiDs, and 72.9% were refractory to both IMiDs and bortezomib. 92.9% were refractory to their last treatment. The median dose of pomalidomide was 4mg (2-4). Grade 3-4 non-haematological toxicities occurred in 42.4%: pneumonia (16.5%), neutropenic sepsis (8.2%), and acute kidney injury (7.1%), were most common. Grade 3-4 neutropenia occurred in 38% and thrombocytopenia in 24%. Seven patients died on treatment, 6 during the first cycle (2 PD and sepsis, 2 neutropenic sepsis, 1 PD and AKI, 2 pneumonia). In the 70 patients assessable for response, ORR was 52.9% (5.7% VGPR, 47.1% PR, 38.6% SD). Median duration of response (DoR) was 4 months. With median follow-up of 13 months, median PFS was 5 months (95%CI 3.6-6.4), and median OS 13 months (95%CI 10.8-15.2). Patients with renal failure (eGFR 65yrs had similar outcomes to younger patients,(ORR 54.1 vs 51.5%, median PFS and OS comparable between groups). Rates of toxicity were also not influenced by renal impairment, adverse genetics, or older age. The most important predictors of PFS and OS were depth and durability of response. PFS was 6 months for patients achieving PR, 4 months for SD and 1 month for PD, while OS was 18 months in patients achieving PR, 13 months for SD and 3 months for PD. For patients with DoR >4 months, PFS was 11 months and OS 23 months. In contrast, in patients whose DoR was < 4 months or who did not respond, OS was 9 months. Conclusions. Our real-world data on the characteristics and outcomes of patients receiving pomalidomide for relapsed/refractory myeloma in the UK reflect results of published clinical trials. The ORR of 52.9% in our cohort is higher than in MM-003 and MM-010, but PFS (5 months) and OS (13 months) were remarkably similar. Rates of haematological toxicity and infections are low, confirming the good tolerability of pomalidomide in this patient group. Depth and sustainability of response were important predictors of survival: achievement of PR was associated with improved PFS and OS, while patients who achieved SD still derived a survival benefit. Patients who maintained a response for at least 4 months had an estimated survival of nearly 2 years. No difference in response, survival or tolerability was seen in key subgroups, including those with moderate renal impairment, adverse cytogenetics and older age. Our findings confirm the efficacy of pomalidomide in these heavily pre-treated patients and add to the evidence for the benefit of pomalidomide in high risk patient groups. Table Patient characteristics and comparison with MM003 trial Table. Patient characteristics and comparison with MM003 trial Figure 1 PFS and OS for the edited group of 70 patients Figure 1. PFS and OS for the edited group of 70 patients Disclosures Maciocia: Autolus: Equity Ownership, Patents & Royalties: TRBC1 and 2 Targeting for the Diagnosis and Treatment of T-cell Malignancies. Ramasamy:Celgene: Honoraria, Research Funding. Jenner:Novartis: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Other: Travel support; Amgen: Consultancy, Honoraria, Other: Travel support; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel support, Research Funding. Schey:Celgene, Takeda: Honoraria; Celgene, Johnson & Johnson: Speakers Bureau; Celgene: Consultancy. Yong:Autolus Ltd: Equity Ownership, Patents & Royalties: APRIL based chimeric antigen receptor; Janssen: Research Funding.

Background. Chemotherapy followed by ASCT is standard of care in fit transplant-eligible newly diagnosed patients with Multiple Myeloma (MM). Most patients, however, will relapse and require further treatment. With increasing choice of therapies at relapse, we need to understand the determinants of treatment outcomes for these patients, to aid management decisions and patient counselling. Methods. This was a retrospective analysis of sequential patients who relapsed from upfront ASCT carried out between 2000-2014. PFS1 was defined as time from ASCT to 1st progression or death; PFS2, time from ASCT to 2nd progression or death and 2nd PFS, time from start of salvage regimen to 2nd progression or death. Post relapse survival (PRS) was measured from progression date and overall survival (OS) from ASCT date. Disease response, and adverse FISH were assigned according to IMWG. Survival was estimated using Kaplan- Meier curves and correlative analysis by Cox regression models. Results. Of 474 patients undergoing ASCT (2000-2014), 277 relapsed with a median age of 58 years (range 29-70).The M:F ratio was 1.85:1. Isotypes identified were: IgG 57.0%, IgA 22.7%, light chain 15.9%. Median PFS1 from ASCT was 20 months (0.47-128.3). ORR pre-ASCT was 91.3% (sCR/CR 4.4%, VGPR 25.4%) and post ASCT was 95.3% (sCR/CR 14.5%, VGPR 52.2%). At relapse, median age was 60 years (30-73) and 36.5% of patients had ISS stage2-3 disease. For the 277 patients who relapsed, median OS from ASCT was 67 months (CI 57-73) and median PRS was 40 months (35-44). PFS1 had a strong influence on OS, HR 0.97 (95%CI: 0.96-0.97, p Patients relapsing before 2008 (prior to bortezomib funding) had shorter OS compared to those relapsing thereafter: median 61 vs 69 months, HR 1.38 (1.01-1.87, p=0.04). Depth of response (CR/VGPR) pre and post-ASCT were associated with longer PFS1- HR 0.70 (0.54-0.92, p=0.01), and HR 0.68(0.51-0.89, p=0.005) respectively, but not OS or PRS. 248 patients (89.5%) received systemic salvage therapy at relapse;106 patients (38.3%) experienced biochemical IMWG progression rather than clinical relapse, with median time to treatment of 5 months (2-64). Salvage regimens included: proteasome inhibitors(PIs) (64.5%), immunomodulatory agents (IMiDs, 29.8%, thalidomide-63.5%, lenalidomide-36.5%) and chemotherapy 5.2%; 26.6% of patients entered clinical trials and 13.7% underwent salvage ASCT. ORR was 70.4% (sCR/CR 10.9%, VGPR 31.6%). Median 2nd PFS was 17 months (16-20) and median PFS2 overall was 39 months (35-41). Achieving a deeper response to salvage treatment (CR/VGPR) was associated with a longer 2nd PFS (21 vs 17 months for PR, HR 0.65, 0.46-0.91, p=0.01), with a trend for PRS, HR 0.89(0.59-1.34, p=0.58) and OS, HR 0.77(0.51-1.17, p=0.22). Novel agents induced deeper responses, CR/VGPR with PI regimens 51.3%, with IMiDs 30%, and with chemotherapy 8%. Patients treated with PIs compared to all other systemic treatment regimens had a significantly longer OS of 80 vs 48 months, HR 0.60(0.43-0.85, p= 0.004). Patients entered into clinical trials (66) had deeper responses, ≥VGPR 61% compared to 31% in non-trial patients, and longer PRS, 64 vs 35 months, HR 0.54 (0.36-0.81, p= 0.003) and OS 90 vs 57 months, HR 0.50 (0.33-0.76, p=0.001). Risk factors at relapse influenced outcomes. Higher ISS was associated with shorter PRS, ISS 2/3 27 vs 50 months for ISS1, HR 2.52(1.74-3.66, p Conclusions. This real-world series shows that timing of relapse, period of relapse (pre-2008), ISS Stage, adverse FISH, and response to salvage regimen influence survival after relapse from frontline ASCT. Use of novel regimens, particularly PIs as salvage therapy post ASCT is associated with longer OS. Our data confirm the importance of entering patients into clinical trials. Multivariable linear regression analyses will be presented. Lastly, the inferior outcomes for patients with high-risk features highlights the need to develop different treatment strategies in this patient subgroup. Disclosures Maciocia: Autolus: Equity Ownership, Patents & Royalties: TRBC1 and 2 Targeting for the Diagnosis and Treatment of T-cell Malignancies. Yong:Janssen: Research Funding; Autolus Ltd: Equity Ownership, Patents & Royalties: APRIL based chimeric antigen receptor.