ALBERT

Beschreibung: Abstract 1364 In light chain (AL) amyloidosis, as well as in multiple myeloma, response to treatment is increasingly being used as a surrogate endpoint in clinical trials. In 2005 a consensus statement of the International Society of Amyloidosis (ISA) established the criteria for hematologic and organ response. Since then, several studies emphasized the prognostic relevance of the measurement of the amyloidogenic precursor, the circulating free light chain (FLC). Moreover, it was reported that patients who with treatment achieved decreases in the cardiac biomarker N terminal natriuretic peptide type B (NT-proBNP) had longer survival, although echocardiographic criteria of response were not attained. The ISA Consensus Panel reconvened in 2010 to update hematologic and organ response criteria. The panel felt that any new criteria should be validated in a large patient population. Thus, we systematically gathered from 7 referral centers in Europe and in the United States a cohort of 649 patients with systemic AL amyloidosis who had been evaluated for hematologic and organ responses at diagnosis and 6 months after treatment initiation, excluding patients who died earlier. At diagnosis, 430 patients (66%) had heart involvement, 377 (58%) had NT-proBNP ≥650 ng/L, 455 (70%) had renal involvement (95, 15%, with glomerular filtration rate 30% and 〉300 ng/L, and a threshold of evaluability based on NT-proBNP baseline level 〉650 ng/L was chosen. The most powerful criteria for PR were those based on dFLC percent decrease, and a 50% cutoff was preferred because of easier clinical use. Among candidate criteria for VGPR, the best were based on iFLC absolute value achieved after therapy, but the performance of those based on dFLC absolute value was only slightly lower. Therefore, a definition of VGPR based on dFLC (

Beschreibung: The prognosis of patients with systemic AL amyloidosis is mainly driven by advanced organ dysfunction, mainly heart involvement. The contribution of the underlying plasma cell clone to prognosis has not been much studied – lately the serum free light chain load has been shown to impact survival. Detailed analysis of plasma cell immunophenotype by multiparameter flow cytometry has been reported to be prognostic in myeloma as well as MGUS. We report that the plasma cell phenotype may allow us to refine prognostic assessment in patients with systemic AL amyloidosis. 48 serial patients with biopsy proven systemic AL amyloidosis had bone marrow as part of a prospective bone marrow study. Flow cytometry was done using previously published protocols (Paiva et al Blood 2010) using fluorescent labelled monoclonal antibodies to the following markers (maximum eight in one tube): CD138, CD38, CD56, CD117, CD28, CD20, CD27, CD19, CD81 and kappa and lambda light chains. Organ involvement, survival and haematological response were analysed in the context of plasma cell phenotypes. Abnormal plasma cell phenotype was defined as cells expressing CD38+CD138+CD19- and further markers were analysed on this population. Cardiac, renal and liver involvement in the cohort was 69%, 75% and 29% respectively. The median follow up was 7 months (range 0.7-18.7months). Results Cardiac involvement was significantly higher in patients co-expressing CD56 (spearman’s correlation coefficient = 0.342 and p=0.021) and a non-significantly greater in those with CD27 expression. 77% had achieved a haematological response on an intention to treat analysis with 65% achieving a VGPR or better. Patients with plasma cells lacking expression of CD27 or CD81 achieved a significantly higher rate of VGPR or better compared to those expressing these markers, (spearman’s correlation coefficient = -.565 and -0.394, p=0.001 and p=0.021 respectively) (Table 1). Median OS was not reached for the whole cohort and the 2 year OS in patients with 〉5% normal plasma cells (defined as CD38+CD138+CD19+ plasma cells) was 74% compared to 45% in those with 5% normal plasma cells had a better median OS compared to those with

Beschreibung: Abstract 2966 Introduction: Poor survival in AL amyloidosis is largely driven by outcomes in patients with advanced cardiac disease. To date, the Mayo cardiac staging system is the most widely used tool to identify these high risk patients. For stage III patients few treatment options exist to modify the natural history of this disease with up to 50% dying within the first 6 months. Moreover, there are currently no studies comparing different regimens in the novel agent era specifically addressing this group. Here we present a matched comparison examining response and survival endpoints after upfront treatment in Mayo stage III patients using either Cyclophosphamide, Bortezomib and Dexamethasone (CVD) or Cyclophosphamide, Thalidomide and Dexamethasone (CTD), the current standard of care for this disease in the United Kingdom. Patients and Methods: The primary cohort comprises 78 patients (39 in each arm) referred to the National Amyloidosis Centre in London between 2008–2012. All patients had cardiac involvement by the 2005 consensus criteria and all were Mayo stage III. The CVD cohort reflects all patients seen at the NAC with Mayo stage III disease treated with this regimen upfront. Based on baseline NT-proBNP (〉8000ng/L) and dFLC (〉180mg/L) the patients were then matched with a recent cohort treated with CTD as first line therapy. The CVD and CTD regimens were recommended as previously described (1, 2). Dose modifications were at the discretion of the treating haematologist. Both conventional haematologic responses and dFLC responses were examined (3, 4). Overall survival (OS) was calculated by the Kaplan-Meier method and calculated from the start of treatment until death or last follow-up. To correct for the influence of early deaths on response rates a landmark analysis was performed in patients surviving at least 3 months from treatment (n=21 (CVD) and n=30 (CTD)). Results: In the intention-to-treat (ITT) cohort response rates are comparable although there was a trend to higher CR rates with the CVD regimen (table 1). On an ITT basis, there was no statistically significant difference in the 1-year OS (59.4% vs 46.2% for CVD and CTD respectively, p = 0.9, figure 1a). A high rate of early deaths is noted. 23.7% of CVD and 13.1% of CTD patients died within 6 weeks (p = 0.24). 36.8% of CVD and 23.7% of CTD patients died within 3 months (p = 0.22). In the landmark analysis upfront therapy with CVD correlated with an improved 1-year OS (94% vs 62.1%, p = 0.01, figure 1 b). This may be partly driven by the increased CR rate in the CVD cohort compared to those receiving CTD (47% vs 24% respectively, p = 0.03, table 1). Conclusion: Compared with CTD, treatment with CVD was not associated with a reduction in the high rate of early deaths often seen in patients with Mayo cardiac stage III disease. However, these data suggest that survival of patients treated with CVD upfront may be superior among those who remain alive after the first 3 months, consistent with the higher CR rates achieved. While it did not reach statistical significance the high rate of early deaths indicates that further optimisation and better supportive care strategies are required during the early stages of treatment especially with CVD. Ongoing phase III trials are currently underway to address these issues in a prospective manner. The ITT cohort is shown in (A) and the landmark cohort is shown in (B). Solid and dashed lines reflect CVD and CTD treated patients respectively. Disclosures: Wechalekar: Janssen-Cilag: Honoraria.

Beschreibung: Background. Early small studies from our groups and others reported unprecedented response rates (up to 90%, with 65% complete remissions) in patients with AL amyloidosis treated with the combination of cyclophosphamide, bortezomib and dexamethasone (CyBorD). Based on these results CyBorD has become one of the most commonly prescribed frontline regimens in AL amyloidosis outside clinical trials. Subsequently, however, we have shown that this regimen is unable to overcome the poor prognosis of patients with advanced cardiac disease. There is the need of large studies to identify patients who benefit most from this highly effective regime in AL amyloidosis. Patients and Methods. The prospectively maintained databases of the London National Amyloidosis Centre and of the Pavia Amyloidosis Research and Treatment Center were systematically searched for newly-diagnosed patients treated with CyBorD between 2006 and 2013. Results. A total of 230 patients were identified. Median age was 60 years (range 38-85 years). Involved organs were heart (169, 73%), kidney (149, 65%), soft tissues (35, 15%), liver (25, 11%), and peripheral nervous system (6, 3%). Cardiac stage was I in 41 patients (18%), II in 77 (33%), and III in 112 (49%). N terminal pro natriuretic peptide type B (NT-proBNP) was 〉8500 ng/L in 51 patients (22%). Median estimated glomerular filtration rate was 82 mL/min (range 4 - 〉90 mL/min), being

Beschreibung: Abstract 4074 AL amyloidosis is caused deposition of monoclonal immunoglobulin light chain and is associated with IgM-paraproteinemia in 5% of cases – mostly due to underlying Waldenstrom's macroglobulinaemia. The standard treatments for AL amyloidosis are typically regimes derived from multiple myeloma and are inappropriate in this group of patients. Response to alkylating agents is poor and there is no agreed standard treatment. We describe here the treatment and outcome of 297 patients with IgM-related AL amyloidosis, with particular focus on the impact of outcomes when treated with regimes developed specifically for Waldenstrom's macroglobulinaemia. 267 consecutive IgM patients with AL amyloidosis were identified form the databases of amyloidosis groups based in London, UK, Pavia, Italy and Limonges/Tolouse/Paris, France- evaluated between 1988 and 2011. 64% of patients had underlying lymphoma mainly of lymphoplasmocytic subtype; lymph node amyloid was present in 18%. Commonest organ involved was the kidney (64%) followed by heart (42%). Serum free light chain ratio was abnormal in 163 (72%) patients with baseline difference between uninvolved and uninvolved FLC (dFLC) 〉50 mg/L in 124 (54%) cases. 135 patients required therapy, of whom 124 were evaluable for frontline regimen: chlorambucil/melphalan in 57, rituximab-containing regime 60 (23%) (R-CVP, FCR, RCD, R-Bortz, R-CHOP, others), purine analogs in 44 (17%), bortezomib containing 24 (8%), R-CHOP and R-CD in 18 (7%) and 20 (8%). 9 (3%) had high dose melphalan followed by autograft. The haematological response rate on an intention to treat basis was 28% (41% for evaluable patients) with only 2% VGPR or better. Median time to next treatment was 10 months with a better outcome for frontline HDM, CHOP/CVP and FCR (median 49, 16 and 13mo, respectively) with 50% responders. Median OS was 48 months. Presenting dFLC 〉180mg/L was predictive of poorer outcomes - median survival 48 months for patients with dFLC 180mg/L. The Mayo cardiac stage at presentation was strongly predictive of outcomes with median survival of stage 1 – 74 months, stage 2 24 months and stage 3 – 10 months. Although complete response rates were low, there was a significant survival advantage for patients achieving at least a partial response with estimated 3 year survival of 78% for responders vs. 55% for non-responders (figure 1).: There was a survival advantage for patients receiving HDMel, bortezomib combination (median OS not reached) and FCR (78mo) compared to (R)CHOP/CVP or FC regimens (median OS 42 and 31mo). In summary, the overall treatment responses in patients with IgM associated AL amyloidosis are poor. Presenting free light chains and cardiac biomarkers are prognostic factors in patients with IgM associated AL amyloidosis. Patients with IgM related AL amyloidosis should be treated with appropriately tailored regimens for the underlying lymphoproliferative disorder to achieve at least PR. Exposure at some stage to bortezomib, FCR or HDM appears to be associated with better survival. Figure 1: Overall survival stratified by degree of haematological response Figure 1:. Overall survival stratified by degree of haematological response Disclosures: Roussel: janssen: Honoraria; celgene: Honoraria. Wechalekar:Janssen-Cilag: Honoraria.

Beschreibung: Abstract 988 The treatment of patients with systemic AL amyloidosis remains challenging. Cyclical combination chemotherapy is used in majority of patients but a report that I.V. melphalan-dexamethasone may not overcome the poor prognosis for cardiac amyloidosis (Deitrich S et al, Blood, 116, 2010) has fuelled the controversy about best front line treatment. We report outcomes of 428 patients treated with oral cyclophosphamide thalidomide dexamethasone (CTD), oral melphalan dexamethasone (M-dex), bortezomib dexamethasone with or without an alkylator (BD), cyclophosphamide-lenalidomide-dexamethasone (CLD) or stem cell transplant (ASCT) as first line treatment for systemic AL amyloidosis assessed at three large European amyloid centres in London (UK), Pavia (Italy) and Athens (Greece) between 2003–2010. Patients with a full baseline data set were included in the study. Clonal and organ responses were defined according to the international amyloidosis consensus statement (Gertz et al 2005) and responses were assessed at 6 months or at the end of treatment. dFLC (difference between involved and uninvolved free light chain (FLC)) was used to assess the absolute FLC change after treatment. 204 (48%) received M-dex, 155 (36%) received CTD, 13 (3%) received ASCT, 28 (7%) received BD and 25 (6%) received CLD. The median number of cycles received was 5 for all regimens. 257 (60%) had cardiac involvement, 325 (76%) had renal and 59 (14%) had liver involvement. Cardiac involvement by regime was: BD 75%, CLD 68%, M-dex 65%, CTD 45% and ASCT 23%. 30 (7%) died within six months of diagnosis. The median number of organ involved was 2 (range 1–5) with ECOG performance status ≥2 in 123 (28%). 98 (23%) patients achieved a complete response (CR), 175 (41%) achieved a partial response (PR) and 125 (29%) did not respond to treatment. A haematological CR/PR was seen, respectively, in 22%/41% treated with CTD, 26%/44% with M-dex, 23%/46% with ASCT, 39%/42% with BD and 4%/44% with CLD. There was significantly greater reduction in dFLC after BD (median reduction 91% over starting value) compared to CTD (median 81%; p = 0.006), M-Dex (median 83%; p = 0.004) and CLD (median 72%; p = 0.03). There was no significant difference in the median dFLC reduction between patients treated with CTD and M-Dex. 100/325 (30%) had a renal organ response, 17/59 (29%) had a hepatic response and 24/257 (9%) had a cardiac response, and 61 (16%) had a cardiac response by NT-proBNP criteria. The organ and NT-proBNP responses respectively were highest in the cohort treated with BD (53% and 32%) followed by CTD (38% and 12%), ASCT (30%), M-dex (23% and 19%) and CLD (12% and nil). CTD achieved significantly better organ responses compared to M-dex (p=0.0024). At median follow up of 29 months, median overall survival (OS) for the whole cohort has not been reached with 2, 3 and 4 year estimated survival of 75%, 65% and 61%, respectively. When patients with cardiac involvement were considered, those achieving a CR have not reached median OS with an estimated 3 year survival of 89%, those with PR had an estimated median OS of 50 months and the non-responders had a median OS of 21 months. Detailed comparison by Mayo stage will be presented. There was no significant difference in the OS of patients treated with CTD or M-Dex (as compared directly or by centre). In summary, outcome of patients with AL amyloidosis across three major European centres appears comparable. BD treatment achieves significantly lower end of treatment dFLC values compared to CTD, M-dex, ASCT or CLD – which importantly translates into an organ response in over half of all patients receiving BD compared to a third of those treated with CTD and quarter of those with M-dex and further follow up may yet reveal survival differences. Organ responses appear significantly better with CTD compared to M-dex – possibly due to more rapid response to CTD since the end of treatment dFLC values are not significantly different - although this does not translate into a survival advantage. Depth of clonal response appears to be directly linked to improvement in survival of patients with cardiac amyloidosis (including in patients treated with CTD and M-dex) and organ response in general. This study supports the rational for doing urgent phase III studies confirming benefits of bortezomib combination chemotherapy for upfront treatment in AL amyloidosis and the benefit of rapid deep clonal responses in cardiac amyloidosis irrespective of the regimen. Disclosures: Off Label Use: Thalidomide, bortezomib, lenalidomide. Dimopoulos:Celgene: Honoraria; Othro Boitech: Honoraria.

Beschreibung: Abstract 992 Background: There have been few prospective clinical trials in AL amyloidosis; existing prospective studies in this heterogeneous disease have been hampered by small patient numbers due to rarity of the condition, a lack of validated endpoints and high cost. More importantly, they have been subject to considerable bias due to almost complete exclusion of poor prognosis patients. Aims: The aims of this prospective observational study, was to include all patients with systemic AL amyloidosis regardless of age or disease severity, in order to convey a ‘real-world' picture of the disease, its response to myeloma-type chemotherapy regimens, associated toxicity and outcomes in terms of amyloidotic organ function, quality of life (QoL) and survival. Methods: All patients referred to the UK National Amyloidosis Centre (NAC) from 1st September 2009 were screened for participation in the AL chemotherapy study (ALchemy). Patients were eligible if they were newly diagnosed with systemic AL amyloidosis and in need of chemotherapy. At each NAC evaluation (baseline, after completion of 3 cycles of chemotherapy and 6, 12, 18 and 24 months) the underlying clonal disease was assessed by sFLC assay and serum and urine electrophoresis; amyloidotic organ dysfunction/response was assessed according to the international consensus criteria. At baseline patients underwent bone marrow examination, assessment of whole-body amyloid load by 123I-SAP scintigraphy, and completed a QoL questionnaire. Amyloid burden was monitored 6 monthly thereafter, and QoL after 3 cycles and yearly thereafter. Clonal disease assessments were undertaken monthly throughout the duration of the study and toxicity assessments during periods of chemotherapy. Patients received chemotherapy in local hematology centers and regimens and doses were at the discretion of treating physicians. Results: Two hundred and fifty patients were recruited in 2 years; 57% were male. Median age at presentation was 64 years (IQR 57 to 73). At baseline evaluation, which occurred a median of 1 month from diagnosis, 20% of patients had Mayo stage 1 disease, and 40% each had stage 2 and 3 disease. Renal (50%) and cardiac (31%) presentations predominated. At censor, 9 (4%) patients had died prior to starting chemotherapy and 217 (87%) patients had received at least one cycle and were thus considered ‘evaluable'. First-line treatment was with CTD in 168 (77%) cases, 89% of whom received dose attenuation. Nineteen (9%) patients received a melphalan- or bortezomib-based regimen first line. One third of those patients who commenced chemotherapy underwent a regimen change, usually (82%) to one containing bortezomib, either as monotherapy (9 patients) or in combination with dexamethasone and/or cyclophosphamide (47 patients). On an intention to treat basis, 20% patients died before reaching the 3 cycle timepoint and a further 9% were withdrawn or lost to follow up. Among the 154 remaining evaluable patients, the 3 cycle evaluation resulted in continuation of the same chemotherapy regimen in 42% cases, a switch of regimen in 21% cases, and cessation of chemotherapy altogether in 28% cases. At this timepoint, clonal CR, VGPR, PR and NR rates among evaluable patients were 35%, 9%, 30% and 26% respectively. Toxicity ≥grade 3 occurred in 49% of patients with a total of 359 episodes. The commonest severe toxicities were fluid overload (61%), lethargy (38%), infection (26%), hypotension (18%) and neuropathy (12%). Of 217 patients, 111 (51%) were admitted with a total of 148 hospitalizations, most commonly due to fluid overload or infection. After median follow-up of 7 months, 29% of patients had died. Mayo stage 3 disease, dominant cardiac presentation and inadequate clonal response after 3 cycles were independent risk factors for death. Achieving a dFLC response 〉65% after the first cycle of chemotherapy, appeared to overcome the poor prognosis associated with Mayo Stage 3 disease. Conclusion: ALchemy is fast becoming the largest prospective study in AL amyloidosis and has provided a wealth of information on treatment, toxicity and outcome in a real-world clinical setting. The inclusion of most patients, regardless of disease severity, indicates a persistently poor prognosis among a substantial proportion of patients who are ineligible for randomized controlled trials, and highlights the unmet need for improved diagnosis and treatment. Disclosures: No relevant conflicts of interest to declare.

Beschreibung: Bortezomib has shown great promise in the treatment of amyloid light-chain (AL) amyloidosis. We present our experience of 43 patients with AL amyloidosis who received cyclophosphamide, bortezomib, and dexamethasone (CVD) upfront or at relapse. Of these, 74% had cardiac involvement and 46% were Mayo Cardiac Stage III. The overall hematologic response rate was 81.4%, including complete response (CR) in 41.9% and very good partial response with 〉 90% decrease in difference between involved/uninvolved light chain (VGPR-dFLC) in 51.4%. Patients treated upfront had higher rates of CR (65.0%) and VGPR-dFLC (66.7%). The estimated 2-year progression-free survival was 66.5% for patients treated upfront and 41.4% for relapsed patients. Those attaining a CR or VGPR-dFLC had a significantly better progression-free survival (P = .002 and P = .026, respectively). The estimated 2-year overall survival was 97.7% (94.4% in Mayo Stage III patients). CVD is a highly effective regimen producing durable responses in AL amyloidosis; the deep clonal responses may overcome poor prognosis in advanced-stage disease.

Beschreibung: Abstract 3975 Background: Elderly patients with AL amyloidosis present a unique therapeutic challenge. Both the disease itself and other co-morbidities contribute to organ dysfunction, potentially limiting treatment options. Despite this, durable responses can be achieved leading to both improvements in quality and longevity of life. Here we present our experience with patients 〉 75 years (yrs) enrolled in the UK-wide ALchemy study. Patients and Methods: ALchemy was designed to collect comprehensive treatment, outcome and toxicity data in newly diagnosed patients attending the National Amyloidosis Centre in the UK. Analysis of prospectively collected data revealed 46 pts 〉 75 yrs who were enrolled in the study beginning in 2009. 8 patients still alive at last assessment but having 〈 3m follow-up were excluded. Haematologic response was defined as per the 2005 consensus criteria. The dFLC response (difference between the involved and uninvolved free light chain) was defined as the percent difference in the dFLC at the start of therapy and at response assessment and was considered assessable if the baseline dFLC was 〉50mg/L. A dFLC between 50–90% defined a partial response (PR) and a dFLC of 〉90% defined a very good partial response (VGPR). The analysis was performed on an intention-to-treat basis and patients who died prior to response assessment were defined as non-responders. Overall survival (OS) was calculated by the Kaplan-Meier method and calculated from diagnosis until death or last follow-up. Results: The final cohort comprised 38 patients. Median age was 78.0 years. Median follow-up was 8.7 months (m). 37 patients had complete information for Mayo staging and 37% were stage III. 3 patients did not receive therapy. 20 patients received CTD as first line therapy, 4 received Mel/Dex, 4 received MPT, 1 received CVD, 3 received CD, 1 received RCD and 2 received CVP-R given baseline IgM secreting clonal B-cell lymphoproliferative disorders. 46% received less than 4 cycles of the planned upfront therapy. Overall response rate (RR) was 68% (11% attained a CR). 65% attained a partial dFLC response and 22% attained a VGPR. 9 patients received second line therapy. 5 were treated for relapsed disease, none of whom bettered their previous haematologic response but 2 patients attained a VGPR. Of the 4 patients who were treated for sub-optimal response none bettered their previous response. A correlation between receiving at least 3 cycles of therapy and attaining a CR or VGPR was observed (correlation coefficient 0.23, P = 0.09 and 0.42, P = 0.009 respectively). Median OS for the entire cohort was 10.7m. 45% died within one year of diagnosis. Median OS for Mayo stage III patients was 6.2 months. Attaining a VGPR by dFLC criteria correlated with a statistically significant improvement in OS compared with patients who did not achieve this milestone (median not reached vs 9.8m respectively; P = 0.016). A similar trend in OS was seen in patients who attained a CR but this did not reach statistical significance (median not reached vs 9.8m respectively; P = 0.192). Discussion: Treatment of elderly patients with AL amyloidosis remains a challenge. From our analysis despite receiving standard of care, median OS is 〈 1 year. However, based on this study appropriate treatment resulted in both attainment of CRs and VGPRs. Both endpoints are important treatment milestones previously shown to correlate with improved survival, and this is further corroborated here. Median OS was not reached in patients achieving either a CR or VGPR. Unfortunately, CR and VGPR rates remain 〈 25% in this population and it appeared that at least one factor is the inability to complete 3 cycles of treatment. Further study examining this distinct group of patients is warranted with the aim to develop therapeutic regimens balancing both effectiveness and tolerability. Disclosures: No relevant conflicts of interest to declare.

Beschreibung: Abstract 3978 Background: Bortezomib alone and in combination with other agents has shown great promise in the treatment of AL amyloidosis in various preliminary open studies. Here we present our experience at the UK National Amyloidosis Centre with CVD in both the upfront and relapsed setting. Patients and Methods: The primary cohort comprises 37 patients referred to the National Amyloidosis Centre in London from 2006–2010. 27 patients had cardiac involvement by 2005 consensus criteria. 29 had renal involvement, 10 had liver involvement and 26 had other organs involved. Complete information for staging by the Mayo clinic criteria was available in 34 patients, and 47% were stage III based on values obtained prior to the initiation of CVD (23% of upfront patients and 62% of relapsed patients). The recommended CVD regimen was as follows: bortezomib 1.0 mg/m2 IV days 1, 4, 8, 11 (increase to 1.3 mg/m2 if well tolerated) cyclophosphamide 350 mg/m2 po days 1, 8, 15 dexamethasone 20 mg po days 1, 4, 8, 11 (increase to 40 mg if well tolerated) with an aim to deliver 6 cycles of treatment. Dose modifications were at the discretion of the treating haematologist. We aimed to assess response at 6 months (m). Haematologic and organ responses were defined as per the 2005 consensus criteria. The dFLC response (difference between the involved and uninvolved free light chain) was defined as the percent difference in the dFLC at the start of therapy and at response assessment and was considered assessable if the baseline dFLC was 〉50mg/L. A dFLC of 50–90% defined a partial response, and a dFLC of 〉90% defined a VGPR. Progression free survival (PFS) was calculated by the Kaplan-Meier method and calculated from the start of CVD until relapse, death or last follow-up. Statistical analysis was performed using SPSS version 19. Approval for analysis and publication was obtained from the institutional review board at the University College London, and written consent was obtained from all patients. Results: Median follow-up was 13.3m. Median time to assessment was 5.9m. Median number of cycles given was 4.9. All 37 patients were assessable by haematologic response criteria, 29 of whom were assessable for dFLC response. Overall hematologic response rate (RR) was 78.4% (CR = 35.1%). A VGPR was attained 48.3% of patients with an overall dFLC RR of 79.3%. 14 patients were treated with CVD upfront with a RR of 85.7% (CR = 64.3%, VGPR = 66.7%). 23 patients were treated in the relapse setting and the RR was 73.9% (CR = 17.4%, VGPR = 35.3%). Clonal response is detailed in table 1. 26 patients were assessable for a BNP response based on a pre-treatment NT-proBNP 〉 660 ng/L. BNP responses were seen in 8 patients (31%), stable disease in 14 (54%) and progression in 4 (15%). Of the entire cohort only one death was reported and there were no treatment related mortalities. The time to maximal response was 3.8m (3.0m and 3.8m in patients treated upfront and at relapse respectively). Median PFS has not been reached. The estimated 2-year PFS was 55.6% for the entire cohort, 69.6% for patients treated upfront and 43.8% for those treated at relapse. Attaining a CR correlated with a significant improvement in progression free survival compared with those who had not (median PFS not reached vs. 23.1m respectively, P = 0.029; figure 1A). Attaining a VGPR also correlated with an improved PFS compared with those who had not (median PFS not reached vs. 13.2m respectively, P = 0.003; figure 1B). Conclusion: This retrospective series lends further support to the use of bortezomib containing regimens in the treatment of AL amyloidosis. CVD is a safe and effective treatment option supporting similar findings in other small retrospective series, particularly when used in the upfront setting. This is, to our knowledge, the first series reporting PFS with this regimen. In addition, it confirms the importance of achieving a CR for improved survival outcomes and further validates the dFLC response as an important treatment endpoint. CVD is an attractive treatment combination for patients with AL amyloidosis many of whom are transplant ineligible due to advanced disease. Larger phase III studies are warranted and are underway. Disclosures: Wechalekar: Jansen Cilag: Honoraria.