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BACKGROUND Post myeloproliferative neoplasms (MPN) acute myeloid leukemia (AML) occurs respectively in 1.5%, 7.0% and 11% of patients with essential thrombocytosis (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). This subgroup of AML has very poor prognosis and are often excluded from clinical trials. Therefore, only few cohorts including molecular data are available. MATERIAL AND METHODS We retrospectively collected data from 111 patients treated in four centers in France for post MPN-AML. Clinical, molecular and treatment information was available for all patients at AML and MPN stages. DNA was extracted from samples at diagnosis of MPN chronic phase, at diagnosis of AML phase and after induction treatment. JAK2-V617F mutations were identified by qPCR (Ipsogen® MutaQuant kit, Qiagen, Germany), MPL-W515L/K mutations were identified by PCR (Ipsogen® MutaScreen kit, Qiagen, Germany) and CALR mutations were identified by conventional sequencing (Applied Biosystems, 3500Genetic Analyzer). NGS on 36 genes using Ampliseq librairy and Ion Proton sequencing (Thermofisher, Waltham, MA, USA) were performed in 96/111 patients. Overall response rate (ORR) was defined by complete remission (CR), CR with incomplete hematologic recovery (CRi), partial remission (PR) and stable disease (SD). Overall survival (OS) was calculated from the date of AML diagnosis to the date of death or last follow-up. All statistical analyses were performed using SPSS v.22 software (IBM SPSS Statistics). RESULTS 111 patients treated for post MPN-AML were retrospectively included in this study. Sex ratio M/F was 54%/46%. Median age at AML diagnosis was 66 years (28-89, range). Cytogenetic categories were favorable, intermediate and adverse in 2 (2%), 51 (46%) and 47 (42%) patients, respectively. 25/111 (23%) patients had a monosomal karyotype (MK). Median number of additional mutations excluding from JAK2/MPL/CALR mutations was 2 (0-6, range). The most frequent additional mutations were TP53 (23%), ASXL1 (17%), TET2 (13%), SRSF2 (10%), DNMT3A (8%), SF3B1 (8%) and RUNX1 (8%). Only 2 patients were mutated for NPM1 and 2 and 4 patients were FLT3-ITD and FLT3-TKD, respectively. Prior MPN were PV, ET and PMF in 20%, 34% and 46% of patients, respectively. First line treatment was intensive chemotherapy (IC) for 61 (55%) patients, hypomethylating agents (HMA) for 10 (9%) or other treatments including best supportive care, cytoreduction for the other ones. 24/111 (22%) underwent to ASCT. ORR was 54% (with 30/71 (42%) in CR/CRi) in patients treated by IC or HMA. We did not identify factors predicting a higher rate of CR/CRi. OS was 12 months [6-18] and was not influenced by transplant, cytogenetic categories or by the type and allele frequencies of JAK2/CALR/MPL mutations. OS was significantly longer in the group treated with HMA as compared to IC (10 versus 46 months, respectively, p=0.006); in patients with prior PV as compared to ET or MF (26 months [0-57] versus 10 months [7-13] versus 10 months [4-16] respectively, p=0.07) and in patients with presence of additional mutations other than JAK2/CALR/MPL (5 months [0-12] versus 46 months [32-60] in 38 patients without mutation versus 58 patients with presence of at least one mutation, respectively, p=0.04). By multivariate analysis, only presence of additional mutations was predictive for OS with a hazard ratio (HR) = 0.42 [0.18-0.97] (p=0.04). Finally, we followed the VAFs of JAK2 in seven patients before and after IC. We observed in 2 patients an increase of JAK2 clone correlated with CR whereas no variation of VAFs was associated with absence of CR. CONCLUSIONS In conclusion, we confirmed the poor prognosis of post MPN AML. Classical AML prognostic factors were not validated in our cohort. We identified the presence of mutations other than JAK2/MPL/CALR as the main prognostic factor whereas post-PV AML appeared to do better than post-ET and post-PMF AML. The very poor result of IC with or without ASCT highlights the need to develop specific clinical trials in this subgroup of AML. Disclosures Kuykendall: Celgene: Honoraria; Janssen: Consultancy. Sallman:Celgene: Research Funding, Speakers Bureau. Cluzeau:CELGENE: Consultancy; MENARINI: Consultancy; JAZZ PHARMA: Consultancy.

Introduction Primary CNS lymphoma (PCNSL) is a diffuse large B-cell lymphoma (DLBCL), predominantly of non-germinal center (non-GC) subtype. Currently available treatments remain disappointed with a non-optimal complete remission rate and a high relapse rate. As such, novel therapeutic agents are urgently needed. Constitutive activation of the NF-kB pathway via mutations in B cell receptor (BCR) (CD79B) and mutation of MYD 88 and TBL1XR1 pathways plays an important role in PCNSL. Ibrutinib, an inhibitor of BCR signaling, has been found to have significant therapeutic activity in relapsed or refractory non-CNS non-GC DLBCL that display similar NFKB mutational patterns. We have performed a CNS pharmacokinetic (PK) study of Ibrutinib and evaluated its therapeutic activity against CNS lymphoma (CNSL) in murine models. Methods CNS PK study in mice - The first study was done in a CNSL model created by intracerebral implantation of luciferase-transfected lymphoma cells (MC116) in nude mice in comparison to healthy nude mice without lymphoma cell implantation (N=5 per group). Once the tumor activity was confirmed by bioluminescence imaging in CNSL group, all the mice were treated with ibrutinib 12 or 30 mg/kg/day by oral gavage (OG) for 5 days. Blood and brain were collected 2 hours after the last dose. Ibrutinib was measured by ultra performance liquid chromatography with tandem mass spectrometry. Cerebro-spinal fluid (CSF) PK study in Sprague-Dawley (SD) rats - Ibrutinib 50 mg/kg single dose was given by OG (N=6). Microdialysates of CSF were collected from a ventricle of the brain and a carotid artery via microdialysis catheters every hour for 13 hours post-treatment. Drug concentrations were determined by capillary electrophoresis with laser detection. Preclinical therapeutic evaluation - A murine CNS lymphoma model was created by intracerebral injection of the OCI-Ly10 non-GC DLBCL cells, which were confirmed to have CD79 A and MYD 88 mutations and show high sensitivity to Ibrutinib in vitro. Animals were sacrificed if they showed severe clinical signs or symptoms or >20% weight loss. Ibrutinib 30 mg/kg was administered by OG daily starting at day 7 post-implantation and until the last sacrifice in the control group treated with vehicle. Therapeutic efficacy was determined by Kaplan-Meier survival analysis using date of sacrifice as endpoint. Results CNS PK study in mice - 1) Ibrutinib levels in plasma, normal brain tissue and brain-tumor were analyzed. Ibrutinib was not detected in healthy control mice treated with vehicle. In healthy mice treated with ibrutinib (12 mg/kg and 30 mg/kg), Ibrutinib mean plasmatic levels were 9.31 (±3.56) ng/mL and 42.2 (±20.9) ng/mL respectively. At 12 mg/kg dose level, ibrutinib was detectable but not quantifiable in brain tissue. After treatment with 30 mg/kg,iIbrutinib mean levels were 0.0077 (±0.0053) and 0.0071 (±0.00483) ng/g tissue in right and left cerebral hemispheres respectively. In CNSL mice treated with ibrutinib (12 mg/kg and 30 mg/kg), Ibrutinib mean plasmatic levels were 12.03 (±9.04) ng/mL and 42.64 (±42.04) ng/mL respectively, brain ibrutinib levels were 0.008 (±0.005) and 0.007 (±0.003) ng/g tissue for tumor-bearing right hemisphere and non-tumor bearing left hemisphere respectively for 30 mg/kg, while brain ibrutinib level was detectable but not quantifiable at 12mg/kg. CSF PK study in SD rats - CSF penetration of ibrutinib was determined to be ~5.2 % as calculated by area under the curve (AUC) ratio of CSF and blood samples. Cmax in CSF is ~0.35 uM, which is significantly higher than published EC50 concentrations for DLBCL cell lines. Preclinical therapeutic evaluation -Ibrutinib showed an excellent therapeutic activity with significant prolongation of survival (p=0.0137) (fig 1). At a median follow-up of 112 days, the median survival in treated CNSL group is 56 days compared to 33 days in the control group. At the end of the follow-up 33% of animals in treated CNSL group are still alive without treatment. Conclusion Ibrutinib achieves high concentrations in brain and CSF in murine CNS PK models with promising single-agent preclinical therapeutic activity against CNS lymphoma in a murine model. Further studies to develop combination regimen are ongoing. Figure Figure. Disclosures Soussain: Roche: Research Funding; Celgene: Research Funding; Pharmacyclics: Research Funding.

Background. Waldenstrom's macroglobulinaemia (WM) is a B cell lymphoproliferative disorder which is characterised by the production of monoclonal IgM (m-IgM). Response assessment is reliant upon reductions in the m-IgM as measured by serum protein electrophoresis (SPEP) or nephelometric/turbidimetric total IgM (tIgM) measurements alongside lymphadenopathy / splenomegaly assessment. Response assessment guidelines include reductions of 90% (very good partial response, VGPR), 100% with negative immunofixation (complete response, CR) with progressive disease being described as a >25% increase in m-IgM. However, quantitation of m-IgM is not without limitations. The pentameric form of IgM has a molecular weight of >900 kDa, which may be responsible for its tendency to self-aggregate which causes issues in the accuracy of quantitation by SPE. tIgM values are systematically greater than measurement by SPEP densitometry and unable to discriminate between m-IgM and polyclonal IgM as serum concentrations approach the normal range (~2 g/L). Recently novel immunoassays quantifying the heavy / light chain partnership for IgM (IgMκ / IgMλ) have become available, here we report on the performance of the assay in a population of Waldenstrom's patients. Methods. Diagnostic serum was available for 78 WM patients (48IgMκ / 30IgMλ); longitudinal samples were available for 25 patient (median 9 samples, range 3-20), median 1146 days (min 62, max 2220). Sera were analysed retrospectively using the IgM Hevylite immunoassay (Binding Site, UK) on a SPAPLUS (Binding Site, UK) analyser. Results were compared to SPEP / Immunofixation (Sebia, Hydrasys II), tIgM (Binding Site, UK) and established normal ranges (IgMκ: 0.19-1.63 g/L; IgMλ: 0.12-1.01 g/L; IgMk/IgMl ratio: 1.18-2.74; total IgM: 0.5-2 g/L). dHLC (monoclonal isotype IgM HLC – uninvolved isotype IgM HLC) was used as an assessment of m-IgM. Substantial equivalence was assessed by Weighted Kappa (WK, >0.81 considered to be agreement between methods) Results. At presentation all WM patients had an abnormal IgMκ / IgMλ ratio (IgMκ median 140, range 9-2850; IgMλ median 0.1, 0.001-0.9), 2/48 IgMκ and 9/30 IgMλ patients were not quantifiable by SPEP and 4 patients had m-IgM within the normal tIGM normal range. There were considerable differences in the m-IgM concentration as measured by the three tests. IgMκ SPEP (median 13.52g/L, range 0-52.0g/L), tIgM (18.15g/L, 3.28-65.4g/L) and IgMκ HLC (21.2g/L, 2.82-126g/L); IgMl SPEP (median 10.62/L, range 0-39.88/L), tIgM (11.30/L, 1.40-65.40/L) and IgMl HLC (13.4g/L, 0.77-67.4g/L). However, responses assigned by the test during follow-up were remarkably consistent (see table 1) SPEP v dHLC WK 0.84 (s.e. 0.045 95% c.i. 0.75-0.93), tIgM v dHLC WK 0.86 (s.e. 0.04 95% c.i. 0.78-0.94),. Interestingly, IgMκ / IgMλ ratios indicated residual disease in 5/25 patients in whom electrophoresis indicated a CR, in 2/5 of these patients the abnormal ratio was driven by a suppression of the uninvolved HLC IgM. Furthermore, in 7/25 patients tIgM values fell within the normal range during monitoring, and IFE was required to confirm m-IgM. In 7/7 patients IgMκ / IgMλ ratios remained abnormal. Conclusion. Quantification of m-IgM can be problematic not assisted by the poor agreement between methods and method specific limitations. To adequately evaluate patients SPEP, IFE and tIgM are all required to overcome these issues; in our study these could be replaced using IgM HLC. Furthermore the sensitivity to detect residual disease appeared to be greater when looking at IgMκ / IgMλ ratios than when using electrophoretic techniques. This may be due isotype matched pair suppression which has been shown to be prognostic in other B cell disorders including MGUS and Multiple Myeloma. Further studies are required to thoroughly evaluate the role of IgM HLC and pair suppression in WM. Table 1: Comparison of response assignment using electrophoretic techniques (SPEP/IFE), total IgM / IFE (tIgM/IFE) to IgM HLC. 25 patients were followed for up to 2220 days, with multiple responses / relapses assigned. Weighted Kappa (WK) was used to compare response assignments, WK>0.81 is considered agreement. WK SPEP/IFE v IgM HLC 0.84 (s.e. 0.045 95% c.i. 0.75-0.93), tIgM v dHLC WK 0.86 (s.e. 0.04 95% c.i. 0.78-0.94). Disclosures Leblond: Roche: Honoraria, Speakers Bureau.

Background Immunoglobulin D (IgD) multiple myeloma represent uncommon immunoglobulin isotypes, accounting for 2% of cases with limited information is available regarding the prognosis of these isotypes. They have been considered to have a more aggressive course than the more common Immunoglobulin of IgG and IgA isotypes in the era of conventional chemotherapy. Several studies have reported the outcome of IgD MM after autologous hematopoietic stem cell transplantation (ASCT) in recent years, but none in the context of novel agents currently the backbone of almost all if not all lines of therapy upfront. We sought to study the prognostic impact of novel agents used upfront on IgD MM treated in several IFM (Intergroupe Francophone du Myélome) centres. Method This study has included a group of 21 patients with IgD MM that were treated from 1994 to 2012 across 5 IFM centres. IgD MM was diagnosed as outline in international consensus criteria. Response and survival criteria were used as depicted in the IMWG consensus criteria published. Results Median age was 59 years (min max 38-80), sex ratio was 1.7, 75% had lambda light chain, 65% had severe bone disease and 20% one to 3 bone lesions, 55% had severe renal insufficiency, 30% had hypercalcemia, 55% profound anemia. Finally, 39% had adverse FISH either del17p or t(4;14) on bone marrow plasma cells and 50% were ISS 3 with beta2M greater than 5mg/L. 80% had receive novel agents containing regimens upfront, including 70% in the context of ASCT and 75% a bortezomib-based regimen. Overall, 65% reached at least VGPR with a median time to first response at 4 months (IQ 1-5). IgD MM had a greater chance to reach VGPR on bortezomib-based regimen, 80% versus 50% for patients on thalidomide-based regimen; furthermore, ASCT also improved the depth of response rate with 85% versus 20% that reached VGPR, respectively (p=0.022). The presence of renal insufficiency at initiation did not affect the incidence and depth of response rate as expected. With a median follow-up of 65 months, 40% have relapsed and 35% have died. The median TTP and OS was 3 years (CI95% 3;7) and 6 years (CI95% 5;9), respectively. Although not significant due to the limited number of patients the median OS was much shorter in the group treated with conventional agents as to novel agents, 5 years (2;8) versus not reached with a 6-year event free of 53%. Similarly, the patients that have received a thalidomide-based regimen upfront had a shorter OS as to bortezomib-based regimen, 1.9 years (1;nr) versus 5.8 years (2;9) although not statistically significant. Interestingly, ASCT improved TTP but not OS, with 1.6 years (1;2.5) versus not reached (6-year event free is 63%) as median TTP in patients non ASCT and ASCT, respectively (p=0.045). Conclusion Despite the retrospective analysis and the small number of patients, our study showed that the use of ASCT and bortezomib-based regimen improve the prognosis of IgD MM. This data analysis confirms that IgD MM should be treated according to current guidelines upfront that recommend use of a bortezomib-based regimen in the context of ASCT in fit patients. Treatment options including the role of consolidation and maintenance may further improve the outcomes of these patients. Disclosures: No relevant conflicts of interest to declare.

Invasive aspergillosis (IA) remains a major concern among patients with hematological malignancies who receive cytotoxic chemotherapy or allogeneic stem cell transplantation (allo-SCT). With a view toward better understanding the differences in terms of clinical significance and outcomes of IA between allo-SCT recipients and patients treated for leukemia, we report a single-center study of 739 unselected consecutive patients treated in our unit between August 2000 and February 2004. IA episodes were classified according to the 2008 EORTC/MSG criteria. Patients were hospitalized either for allo-SCT (n=135), or for the treatment of acute leukemia (n=378), chronic lymphocytic leukemia (n=116), or myelodysplasic syndrome (n=105). Probable or proven IA were observed in 29 patients, among whom 7 were undergoing allo-SCT (5.2%), 20 were treated for acute leukemia (5.3%), 1 for chronic lymphocytic leukemia (0.8%), and 1 for myelodysplastic syndrome (0.95%). Most of the clinical signs were mild and nonspecific, especially in allo-SCT recipients. Chronologically, thoracic computerized tomography (CT) showed the first signs of IA in 38% of cases, and was positive the same day as at least one biological test (bronchoalveolar lavage [BAL] and serum galactomannan antigen) in 41% of cases. BAL was contributive to the diagnosis in 66% of the 29 cases. Comparison of patients undergoing allo-SCT to the others revealed significant differences. In allo-SCT recipients, the onset of IA occurred later than in the other patients, after the neutropenic period. The median time between the last hematologic treatment and the diagnosis of IA were 231 days (range, 68-341) in allo-SCT recipients and 17 days (6-57) in the other patients (p First line therapy was liposomal amphotericin B (n=22), caspofungin (n=8), voriconazole (n=6), or itraconazole (n=1), either alone (n=21) or in combination (n=8). Complete remission of IA on CT was observed in 12 cases, stable lesions in 8 cases and progression in 9 cases. Mortality directly related to IA was 24% in our study and occurred early after the onset of infection. The 100-day, 1-year, 2-year and 10-year overall survival (OS) were 42.9%, 28.6%, 0%, 0% for allo-SCT recipient, respectively, compared to 68.1%, 40.9%, 18.2%, 13.6% for the other patients, respectively (P-values ≥ 0.05). These poor outcomes were mainly attributable to the non-relapse mortality (NRM), especially in allo-SCT recipients, who had a 2-year NRM of 100% compared to 54.6% in the other patients, p=0.034 (2-year cumulative incidence of relapse were 0% and 70.2%, respectively). In conclusion, our data seem to distinguish 2 types of IA. One has an early onset in neutropenic leukemia patients. The second, observed in allo-SCT recipients, occurs later, after GVHD development and is associated with a very high NRM incidence, suggesting that those patients remain fragile. Thus, systematic broad-spectrum anti-fungal prophylaxis is highly recommended in patients undergoing allo-SCT who develop GVHD. Disclosures: Berthon: CELGENE: Research Funding.

Abstract 2964 Background. Lenalidomide is an oral IMiD®, immunomodulatory compound, approved for use in combination with dexamethasone (Len/Dex) in patients with RRMM who have received one prior therapy. Len/Dex is indicated until evidence of disease progression at the best-tolerated dose of both Len and Dex (Dimopoulos et al. Leukemia 2011). However, the tolerability profile of long term exposure to Len/Dex is not well described, and evidence that long term exposure to Len/Dex would improve on the response rate and survival has yet to be determined. We sought to determine the efficacy and safety profile of long term exposure to Len/Dex in RRMM pts in a multicentre study. Method. We retrospectively reviewed the medical records of 50 RRMM pts treated with Len/Dex and remaining on Len for ≥2 years with a special focus on pts receiving Len for ≥3 years. All pts included had complete follow up records. Results. The median (range min-max) age was 58 years (39–79) with 30% (n=15) > 65 years (elderly MM), the sex ratio M/F was 1.2, 49% (n=24) ISS 2 and 3, 12% (n=6) severe renal insufficiency (CrCl < 30mL/min), and 8% (n=4) adverse FISH [del17p and/or t(4;14)]. Overall, 25 pts (50%) had Len/Dex at first relapse, 19 pts (38%) at second relapse and 6 (9%) pts in subsequent relapses. Len/Dex was given at first relapse in 10 (66%) elderly patients. The median time from diagnosis to starting Len/Dex was 4.5 years (1–16) for overall cohort and 3 years (1–8) for elderly patients (p=0.05). 28 pts (56%) received Len/Dex for ≥3 years. The median duration on Len/Dex was 3 (2–7) years for the overall cohort, and was 4 (3;7) years for patients exposed to Len ≥3 years. Treatment duration was similar across age categories and across number of previous relapses. With a median follow up of 4 years, 19 patients had stopped Len/Dex. The response rate (ORR, ≥PR) was 96% (n=48), including 37 (74%) patients with ≥VGPR, similar across age categories. Interestingly, the ORR and ≥VGPR were similar irrespective of whether patients have stopped Len/Dex in our study. The ORR was also similar across number of previous relapses, but the ≥VGPR rate was lower in patients at third relapse and beyond, (50%; p=ns). The ORR and ≥VGPR rate was 93% and 77% in patients exposed to Len ≥3 years, similar to the whole cohort. The median time to first response and best response were 2 (1–5) months and 4.5 (2–9) months, respectively. Overall, 9 (18%) patients stopped treatment due to toxicity, 9 (18%) progression of MM, and 1 (0.5%) patient decision. With a median follow up of 4 years, the median (95%CI) TTP was not reached, the estimated 4-yr TTP was 51.5%. There was no imbalance in the incidence of toxicity based on age, number of previous relapses, and patients exposed to Len ≥3 years did not discontinue more often due to toxicity, 14% versus 19% for those receiving Len < 3 years. The hematological safety profile was similar across age categories, number of previous relapses, and patients exposed to Len ≥ 3 years; overall, 8 (16%) patients experienced grade 3–4 neutropenia, 6% thrombopenia, and 6% anemia. Ten (20%) patients experienced a thromboembolic event (VTE), all of them of venous type. Two patients had previous history of VTE, but none of them experienced VTE on Len/Dex, likely related to adequate VTE prophylaxis. The median time to first occurrence was 5 (1;28) months, although 4/10 occurred in patients with ≥3 years on Len. All VTE occurred while on VTE prophylaxis except for 1 patient, 5 on aspirin, 2 on prophylactic doses of LMWH, and 2 on VKA (target INR 2–3). The incidence rate of second primary malignancy (SPM) was 3 (6%) (larynx, lung, and MDS). The SPMs occurred at a median time of 4 years from start of Len, while Len was already stopped in 2/3 patients, the latter stopped len at time SPM was diagnosed. Interestingly, none of the patients with more than 3 years exposure on Len had SPM. Conclusions. The current study provides estimates of responses, TTP and safety in a series of MM pts with long-term exposure to Len-based regimen at relapse. 62% of patients remained on Len beyond 3 years reflecting the efficacy and good safety profile of Len in relapsed MM, irrespective of age and number of prior therapies. Furthermore, no excess of long term side effects, including SPM, was observed with a prolonged long follow-up in this study. Disclosures: Robinson: Celgene: Employment. Miljkovic:Celgene: Employment. Morel:Celgene: Employment. Boccacio:Celgene: Employment. Facon:millenium: Membership on an entity's Board of Directors or advisory committees; janssen: Membership on an entity's Board of Directors or advisory committees; celgene: Membership on an entity's Board of Directors or advisory committees; onyx: Membership on an entity's Board of Directors or advisory committees. Hulin:celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; janssen: Membership on an entity's Board of Directors or advisory committees. Leleu:Onyx: Honoraria, Speakers Bureau; Sanofi: Honoraria; Amgen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Janssen: Honoraria, Research Funding, Speakers Bureau; Celgene: Honoraria, Research Funding, Speakers Bureau; LeoPharma: Honoraria, Speakers Bureau.

Abstract 3970 Background: Measurement of serum M-spike is used to assess response to therapy and treatment-free survival in IgA myeloma. However, its resolution on SPEP and the presence of IgA-dymers can make accurate measurement difficult. The more the M-spike decreases on SPEP, the more imprecise the M-spike measurement is using SPEP. IgA M-spike often migrates in the betaglobines that renders the M-spike measurement often complicated to analyze. Furthermore, quantification of the clonal IgA chain by nephelometry (IgAneph), which inherently includes monoclonal and polyclonal immunoglobulins, does not accurately reflect the tumour burden. Currently, there is a need in myeloma with IgA isotype (approximately 30–40% of patients) to identify new markers that better reflect the disease burden and the response to treatment, and correlate to patients' outcome. Hevylite® measures IgAkappa and IgAlambda and might provide precise quantitative measurement of the IgA M-spike. We sought to determine whether Hevylite® can be used as a reliable marker for diagnosis and response to therapy in IgA myeloma as compared to the M-spike measurement on SPEP and nephelometry. Methods: We conducted a retrospective analysis on 113, smoldering or symptomatic, IgA myeloma patients at diagnosis referred to our department from 1997 to 2011. All serum samples were collected prior to treatment or at relapse (for sequential data) and were kept frozen since collection. Hevylite® measurements were made at The Binding Site Ltd, Birmingham, UK. A normal range was produced from normal (blood donor) sera (n=138), and were for IgA kappa 0.48–2.82g/L, IgA lambda 0.36–1.98g/L and IgA K/L ratio 0.80–2.04. For ease of comparison we have studied the IgA hevylite ratios expressed as IgA K/L ratio. Results: The median age at diagnosis was 65 years (range: 33–93) and the M/F sex ratio was 0,91. Forty-eight percent of patients had an ISS greater than 2 (n=86). On nephelometry the median IgA level was 22g/L (range min-max, 0–100). Fifty patients had M-spikes migrating among the betablobulines, 27 among the gammaglobulines, 10 migrated in both and 23 unspecified. Fourteen patients had oligosecretory disease (M-component < 10g/L). Forty-two patients had an IgA kappa clonal chain, 70 others an IgA lambda and for one patient the data was not available. Among IgA kappa patients the mean HCLratio was 616.6 (median 117.7 [0.021–4323.7]) whereas it was 0.61 (0.21 [0.004–0.455]) among the IgA lambda patients. Across the entire population, 58 patients were identified by SPEP and HCL ratios. Among the 55 patients whose M-component was not quantified on SPEP, HCL ratios were abnormal in 53/55 (96%) cases. In the subgroup of patients whose M-protein migrates in the beta-region 29 out of 50 are identified by HCL ratios and SPEP. Another 19 patients (38%) had abnormal HCL ratios while unquantified on SPEP. The same was seen in patients whose M-protein migrates among the gammaglobulins with 16/27 and 11/27 (40%), respectively. In the last subgroup of patients with beta and gamma migrating M-proteins, all (10/10) were identified by HLC and SPEP. More interestingly, among the oligosecretory MM patients identified by an M-component < 10g/L, all (14 patients) had an abnormal HCL ratio. In our series of IgA myeloma, 51% of patients were accurately quantified on SPEP. When using HCLratios, an extra 47% of patients became measurable, with an abnormal HLC ratios allowing IgA myeloma in up to 98% of cases. When considering IgA measurement using nephelometry, 102 patients had both high IgA levels (90%) and abnormal HCL ratios. Interestingly, 7 patients had normal IgA levels with IgAneph and abnormal HCL ratio offering a useful diagnostic tool for 96% of patients as compared to IgAneph. In our series, IgA myeloma was neither associated with a poor outcome (median [range] OS: 119 months [0,5–604]) nor a poor response to therapy (median [range] TTP: 16 months (1–92). HCL involved chain ROC analysis identified a 37g/L cut-off as prognostic in IgA myeloma(p=0.039). Conclusion: Hevylite® is a new and reliable marker for diagnostic and monitoring of IgA myeloma. It enables to quantify accurately up to 98% of IgA-MM patients. These preliminary data need confirmation in further prospective trials in order to monitor further the impact of this marker in IgA myeloma patients before it becomes the gold standard to monitor the IgA M-protein in years to come. Disclosures: Boyle: Chugai: Consultancy, Honoraria. Combat:The Binding Site: Employment. Pietrantuono:The Binding Site: Employment. Facon:onyx: Membership on an entity's Board of Directors or advisory committees; celgene: Membership on an entity's Board of Directors or advisory committees; janssen: Membership on an entity's Board of Directors or advisory committees; millenium: Membership on an entity's Board of Directors or advisory committees. Harding:The Binging Site: Employment. Leleu:Celgene: Honoraria, Research Funding, Speakers Bureau; Janssen: Honoraria, Research Funding, Speakers Bureau; Novartis: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Sanofi: Honoraria; Onyx: Honoraria, Speakers Bureau; LeoPharma: Honoraria, Speakers Bureau.