ALBERT

Description: Background: AL amyloidosis is a rare life-threatening disease arising from a disorder of plasma cells resulting in excessive immunoglobulin free light chains (FLC) that are misfolded, aggregate, and form toxic deposits in vital organs including the heart, kidneys, and liver (Merlini G, et al. Nat Rev Dis Primers. 2018). The primary goal of therapy is to reduce or eliminate the FLC and halt the progression of organ damage and improve function. Measures that can improve hematologic responses may improve organ responses and impact survival. Treatments used in other plasma cell disorders, like multiple myeloma (MM), including autologous stem cell transplantation (ASCT), are commonly used to treat AL amyloidosis. However, there are no approved therapies for AL amyloidosis. Effective treatment, especially for patients with advanced cardiac involvement, remains a high unmet medical need (Merlini G, et al. Nat Rev Dis Primers. 2018; Milani P, et al. Expert Rev Hematol. 2018). Melflufen, a lipophilic peptide-conjugated alkylator that rapidly delivers a highly cytotoxic payload into cells through peptidase activity, is currently under investigation for the treatment of relapsed/refractory MM (RRMM). In the phase 1/2 study, O-12-M1, of patients with RRMM and ≥2 prior lines of therapy, including lenalidomide and bortezomib, melflufen plus dexamethasone showed an overall response rate of 31%, median progression-free survival of 5.7 months, and median overall survival of 20.7 months, with manageable hematologic toxicity (Richardson PG, et al. Blood. 2017; Abstract 3150). The activity of melflufen in RRMM suggests that it may have potential therapeutic applications for patients with AL amyloidosis. OP201 is a planned, phase 1/2, open-label study evaluating the safety and efficacy of melflufen and dexamethasone in patients who have AL amyloidosis and have received ≥1 prior therapy. Study Design: The planned enrollment for OP201 is approximately 46 patients. Patients must have AL amyloidosis and ≥1 prior therapy, which can include 1 prior nontransplant regimen, a prior ASCT, or 1 prior induction regimen followed by a single ASCT (without hematologic progression between induction and ASCT). Other key inclusion criteria include measurable hematologic and organ involvement (cardiac and/or renal and/or liver), Eastern Cooperative Oncology Group performance status ≤2, adequate baseline hematologic and organ function, ≤30% bone marrow plasma cells, echocardiogram with left ventricular ejection fraction ≥45% and electrocardiogram with QTcF interval of ≤470 ms. Key exclusion criteria include evidence of gastrointestinal bleeding, cardiac risk stage 3 with N-terminal pro-brain natriuretic peptide 〉5000 pg/mL, active infection, concurrent symptomatic MM, significant ventricular arrhythmias, and severe orthostatic hypotension. Phase 1 dose escalation will follow a standard 3+3 design, with 3 to 6 patients evaluable for dose-limiting toxicity at each dose level. Patients will receive melflufen intravenously at 1 of 3 dose levels (20 mg, 30 mg, or 40 mg) on day 1 and oral dexamethasone 40 mg (20 mg at investigator's discretion) on days 1 and 2 of each 28-day cycle. Treatment will continue for up to 8 cycles until stable hematologic partial response or better after cycle 4, less than hematologic partial response after cycle 2, nonhematologic or hematologic disease progression, unacceptable toxicity, or physician's determination that it is not in patient's best interest to continue treatment. The primary endpoints for the phase 1 study are safety and identifying the recommended phase 2 dose (RP2D) of melflufen. Phase 2 will include 26 patients (20 phase 2 + 6 phase 1) treated at the RP2D. The primary endpoint for phase 2 is the hematologic overall response rate after 4 cycles of treatment. Key secondary endpoints include pharmacokinetics (phase 1), best hematologic response, duration of hematologic response, organ system-specific response, duration of organ system-specific responses, time to next AL amyloidosis treatment, and overall survival. Disclosures Palladini: Sebia: Honoraria; Celgene: Other: Travel grant; Janssen-Cilag: Honoraria; Janssen-Cilag: Other: Travel grant. Schönland:Prothena: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Medac: Other: Travel Grant; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Lentzsch:Abbvie: Consultancy; Crossfires in hematologic Malignancies: Honoraria; BMS: Consultancy; Takeda: Consultancy; Clinical Care Options: Speakers Bureau; Columbia University: Patents & Royalties: 11-1F4mAb as Anti-Amyloid Strategy; Janssen: Consultancy; Multiple Myelopma Research Foundation: Honoraria; Bayer: Consultancy; Sanofi: Consultancy, Research Funding; Proclara: Consultancy; Caelum Biosciences: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Research Funding; International Myeloma Foundation: Honoraria. Cibeira:Amgen: Honoraria; Celgene: Honoraria; Janssen: Consultancy, Honoraria. Hajek:PharmaMar: Honoraria, Other: Consultant or advisory relationship; Novartis: Other: Consultant or advisory relationship, Research Funding; Janssen: Honoraria, Other: Consultant or advisory relationship, Research Funding; Amgen: Honoraria, Other: Consultant or advisory relationship, Research Funding; Bristol-Myers Squibb: Honoraria, Other: Consultant or advisory relationship, Research Funding; AbbVie: Other: Consultant or advisory relationship; Celgene: Honoraria, Other: Consultant or advisory relationship, Research Funding; Takeda: Honoraria, Other: Consultant or advisory relationship, Research Funding. Jaccard:Celgene: Honoraria, Research Funding; Abbvie: Honoraria; Janssen: Honoraria, Research Funding; Pfizer: Honoraria. Jamroziak:Amgen: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding. Kastritis:Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Honoraria; Pfizer: Honoraria; Prothena: Honoraria; Genesis: Honoraria. Sanchorawala:Proclara: Consultancy, Honoraria; Caelum: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Celgene: Research Funding; Takeda: Research Funding; Prothena: Research Funding. Schjesvold:SkyliteDX: Honoraria; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Wechalekar:Celgene: Honoraria; GSK: Honoraria; Amgen: Research Funding; Janssen-Cilag: Honoraria; Takeda: Honoraria. Thuresson:Oncopeptides: Employment, Equity Ownership. Harmenberg:Oncopeptides: Consultancy, Equity Ownership. Byrne:Takeda: Consultancy; Oncopeptides: Consultancy. Merlini:University of Pavia: Employment.

Description: Background. POEMS syndrome is a rare form of B cell dyscrasia combining a proliferation usually of plasma cells, a polyneuropathy, osteocondensing bone lesions and multiple other clinical signs. The pathogenesis is not well understood but VEGF plays a major role. In patients with one or two sclerotic plasmacytoma and no bone marrow involvement, first line therapy should include radiation. For patients with diffuse sclerotic lesions, bone marrow involvement or absence of any bone lesion and for those who have not demonstrated stabilization of their disease 3 to 6 months after completing radiation systemic therapy is indicated, the most effective being high dose chemotherapy with autologous stem cell transplant (ASCT). Radiation of a single lesion is effective in about every other case and is accompanied by a fairly slow improvement of the neurological symptoms, often after initial worsening. ASCT seems to be accompanied by a number of important complications, in particular engraftment syndrome. Outside these 2 treatments there is no consensus therapy. Lenalidomide (LEN), a drug without serious neurological toxicity, has the advantage of being both anti-angiogenic and cytotoxic to malignant plasma cells (Richardson PG, Blood 2002;100(9):3063-7). We have recently reported a series of 20 French patients with POEMS syndrome treated by LEN with a good efficacy. We now report the first 27 patients of a prospective phase II trial using LEN + dexamethasone (LEN-DEX), 2 cycles preceding radiation or high dose treatment trying to obtain a rapid clinical response and to avoid engraftment syndrome or 9 cycles followed by 1 year LENalone in patients who cannot receive radiation or ASCT. Methods. Newly diagnosed or relapsing patients with POEMS syndrome who needed to be treated were eligible. Patients who can be treated by local radiation or intensive treatment with stem cell support receive two 28 day cycles of LEN 25 mg PO Days 1-21 and DEX 40 mg PO Days 1,8,15,22 before radiation or intensive treatment (Group 1), the other patients receive 9 cycles of the same LEN-DEX (Group 2) and then 12 cycles of continuous low dose LEN (10 mg). LEN dose was tapered to 10 mg for patients with a creatinine clearance between 30 and 50 ml/min and DEX to 20 mg for patients above 75 years of age and for those who were frail patients. Main eligibility criteria included a diagnosis of POEMS syndrome according to criteria by Dispenzieri et al (Am J Hematol 2012;87(8):804-14), an age of 18 or more, a creatinine clearance above 30 ml/min, no prior treatment with or contraindication to LEN and no uncontrolled thrombosis. Serum and plasma VEGF, serum electrophoresis, immunofixation and free light chain measurements were centrally monitored. Neurologic evaluations were performed using the Overall Neuropathy Limitations Scale (ONLS), the Neurological Impairment Scale (NIS) and the 10 meter walk test (10MWT). The primary endpoint was evaluation of the effectiveness of LEN-DEX combination using biological responses (decrease of monoclonal protein and serum VEGF level) and secondary endpoints were clinical and particularly neurological responses. Results. Twenty-seven patients have been included in 12 centres, median age was 61 (range 32-75), the median follow-up was 6.6 months (range 2-24). Eighteen patients were in group 1, with radiotherapy in 10 patients and ASCT in 8 patients; 9 patients were in group 2. Nineteen patients were in first line and 8 already treated. Only 2 patients experienced grade 3-4 adverse events due to LEN (cytopenia) and 2 patients had allergic rashes, no thrombotic event occurred. No engraftment syndrome was noted in the 5 patients already treated with ASCT. To date, no patient have died. Evolution of VEGF median values in serum and plasma, M-spike and dFLC levels and evolution of neurological measurements are reported in table 1. Neurological improvement was very rapid in some patients, using ONLS and 10MWT 11/18 evaluable patients had a neurological improvement after 2 cycles with an improvement of 1 or more of the ONLS score and/or change of 0.1 m/s or more in the 10MWT. Only one patient who progressed after nine cycles received another therapy. Conclusion. This is the first prospective trial of LEN-DEX in POEMS syndrome. This combination seems well tolerated in this disease with a good efficacy on VEGF measurements and rapid neurological improvement in the majority of patients. Updated data will be presented at the meeting. Figure 1 Figure 1. Disclosures Jaccard: Celgene: Drug supply to Trial Other. Tournilhac:mundipharma: Honoraria, Other, Research Funding; GSK: Honoraria, Other, Research Funding; Roche: Honoraria, Other, Research Funding. Moreau:celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Description: Abstract 2934 Introduction: Len combined with Dexamethasone (Dex) is becoming a standard treatment in multiple myeloma (MM). As Len is mainly excreted by the kidneys, its dose should be adjusted according to renal function. Current dosing recommendations are based on a study conducted in non-malignant patients (pts) and on modelling/simulations. To assess whether these recommendations are actually valid in MM pts, we conducted a prospective study evaluating pharmacokinetics (PK), safety and efficacy of Len+Dex in pts with various degrees of renal impairment (RI). We also compared the glomerular filtration rate (GFR) estimated either by the Modification of Diet in Renal Disease (MDRD) dosage (GFR/MDRD) or by the Cockroft and Gault (CG) equation (GFR/CG) for determining Len dosage. Methods: 37 Caucasian pts (median age 65 yrs) with symptomatic MM who had received ≥ 1 previous line of treatment, were enrolled. All had stable renal function over 4 weeks prior to inclusion. They were divided in 5 groups according to GFR/CG at baseline: group 1, 〉 80mL/min (N = 10); group 2, ≥ 50 & ≤ 80 mL/min (N = 10); group 3, ≥ 30 & 〈 50 mL/min (N = 7); group 4, 〈 30 mL/min (N = 5); group 5, chronic hemodialysis (N = 5). Cast nephropathy and light chain deposition disease were documented by kidney biopsy as the respective cause of RI in 6 and 1 of the 17 pts from groups 3, 4 and 5. Pt characteristics were similar, except for pts in group 4 who were significantly older (p = 0.01). All pts received ≥ 3 cycles of oral Len+Dex (40 mg weekly) regimen from Days 1–21 of each 28-day cycle. Len starting dose was defined according to the current dosing guideline, i.e.: group 1 and 2: 25 mg/d; group 3: 10 mg/d; group 4: 15 mg/qod; group 5: 5 mg/d. Blood samples were collected on a dosing day in the first cycle for PK analyses, as follows: at pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 24 h (and 36 and 48 h in groups 3–5) after the Len dose on day 5, and at predose and 2 h (near tmax) after the Len dose on days 9 and 15. Results: Len clearance was highly correlated to GFR/CG (R2 = 0.86, p 〈 0.001). Mean Len clearance declined from 239 mL/min in group 1, to 160, 93, 54, and 41 mL/min, and mean terminal half life was prolonged from 3 h to 5, 7, 10, and 24h in groups 2, 3, 4 and 5, respectively. These findings were consistent with those reported for pts with RI due to non-malignant conditions. The average daily AUC values for groups 2–5 were 103–149% of that for group 1 (1794 h*ng/mL). No difference was found in mean plasma Len concentrations at 2 h post-dose between day 9 (Len alone) and day 15 (Len+Dex) across groups. GFR/MDRD and GFR/CG were highly correlated (R2 = 0.85, slope = 0.89) and similarly predicted Len clearance (slope = 2.38 and 2.15, respectively). When the same cutoff values were used for GFR/MDRD and GFR/CG, the % reduction in Len clearance in groups 3–5 compared with the combined groups 1 and 2 was very similar for GFR/MDRD- and GFR/CG-based renal function classifications. However, a dosage discordance between GFR/MDRD and GFR/CG would occur in 5/32 non-dialysis pts. All the 5 pts would be assigned to a lower starting dose according to GFR/MDRD. The estimated resulting AUC levels would have been reduced to 68–94% of the mean AUC in group 1 from the observed 91–238%. These estimated AUC levels would be considered to be in the therapeutic range. After 3 cycles of Len+Dex, hematological response rate (≥ PR) was 73% (VGPR 27%). Response rates were 70% in pts with 〈 50ml/min. Renal function remained stable in all pts. A total of 22 serious (≥ grade 3) adverse events (SAEs), including 16 hematological SAEs, occurred in 12 pts, leading to dose reduction in 7 cases. Of these, 2 pts would have been assigned to a lower starting dose according to GFR/MDRD. The frequency of SAEs was not significantly increased in group 5 compared to the other groups (60% vs 45%, p = 0.3). After a median follow-up of 10 months, pts had received a mean number of 7.6 ± 4.3 cycles, and 5 had died, because of MM progression in 4 cases. Conclusion: The study demonstrated that the effect of RI on the Len PK in MM patients receiving concomitant Dex was similar to that in non-malignant pts receiving Len alone. The recommended dose adjustments achieved the appropriate plasma exposure with similar efficacy and safety across different renal function groups in MM pts. GFR/MDRD and GFR/CG may be interchangeable for determining the Len dosage. Disclosures: Chen: Celgene Corporation: Employment. Alakl:Celgene Corporation: Employment. Neel:Celgene Corporation: Employment. Jaccard:Celgene Corporation: Consultancy.

Description: Background: B-PTLD is a rare but severe complication observed after organ transplantation. There is no consensus on treatment modalities in this setting but Rituximab monotherapy has been presented as an effective and well tolerated treatment. Long term efficacy is unknown. Aim: We recently published results of the first prospective study on PTLD treatment, using four weekly injection of Rituximab in progressive or non responding tumours after immunosuppression diminution (Blood2006; 107; 3053–7). We present here update results up to 6 years after inclusion. Methods: From may 2000 to December 2001, 43 PTLD after solid organ transplantation have been enrolled in M39037, a franco-belgian multicentric prospective trial. The primary end point was day 80 response rate and one year results were also presented. Participating centres were contacted in order to obtain update data on surviving patients at one year, especially for their tumour status (complete response (CR), partial response (PR) or progressive disease (PD)), date of last information, eventual death and cause of death. Results: At one year, on 43 included patients, 26 were still alive, 12 in CR or Cru, one in PR, 10 in PD and two with insufficient information. At this time, update data are available on eight patients, six were in CR or Cru at one year and two in PD. Five patients died by organ failure (n=1), graft rejection (n=1), sudden death (n=2) or heart biopsy complication (n=1); all but one were in CR at this time. Three patients are still alive and in CR. No relapse has been diagnosed and median survival is 1188 days (with a median follow up of 1689 days for surviving patients). Final analysis on all patients will be presented at the ASH meeting. Conclusion: Rituximab in monotherapy seems to have a durable efficacy on PTLD after solid organ transplantation with a follow up of more than 4,5 years. Complete results will be presented at the ASH Meeting.

Description: Introduction: in large unselected series, the median age of Primary CNS Lymphoma (PCNSL) patients (pts) is about 70 years. In one USA cancer registry study for PCNSL patients (pts) older than 65 years, 14% of them are older than 80 years. Data on clinical characteristics, therapeutical management, toxicity of treatment and outcome of these very elderly pts are limited. Methods: We reviewed PCNSL pts aged of 80 years or older included in the database of the French Oculo-Cerebral lymphoma (LOC) network. From January 2011, this network prospectively recorded all newly diagnosed PCNSL from 22 regional expert centers in France. For this study, 110 PCNSL pts with a histological diagnosis of diffuse large B-cell lymphoma (DLBCL) aged of 80 years or older were analyzed. All medical records were reviewed for clinical and biological characteristics, modality of treatment and supportive care, toxicities and outcome. Results: 110 pts with a DLBCL PCNSL aged of 80 years or older were diagnosed between January 2011 and January 2018 representing 8% of pts available in the LOC database. The clinical characteristics were as follows: 63% of females; median age: 83y (80-92); performance status (PS) according to EORTC scale: 1, 24% of pts, 2, 21% of pts, 3-4, 55% of pts. 23.6% of pts had a CIRS-G grade 3 or 4 in at least one category and 40.9% had a cumulative CIRS-G score more than 6. Diagnosis procedure was biopsy (87%), tumor resection (5%), vitrectomy (4%), CSF cytology (4%). At diagnosis, 9/68 (13%) of evaluable pts had ocular involvement, 13/61 (21%) cerebrospinal (CSF) involvement, 79/110 (72%) involvement of the deep structures of the brain and 35/86 (41%) had elevated LDH level. Median creatinine clearance (CKD.EPI) was 70ml/min (min: 24, max: 102). Treatment was initiated either by a neuro-oncology or a hematology team in 35% and 65% of cases, respectively. Median delay between first symptoms and treatment was 60 days. First line treatment was high-dose (HD) methotrexate (MTX) based chemotherapy (CT) in 85 pts (77%), other chemotherapy regimen in 13 pts (12%) and palliative care in 12 pts (11%). Median number of CT cycles was 3 (1-11) with a median dose of MTX of 3g/m2 (0.5-5.0). Interestingly, no difference of distribution for the main clinical and biological characteristics (median age, PS, symptoms, tumor localization, albumin level, creatinine clearance) was observed between these three groups. Rituximab was used in combination with CT in 53/98 treated pts (54%). After first-line induction chemotherapy, response rate for evaluable patients (n=85) were as follows: 37% of complete response, 9% of partial response, 54% of stable or progressive disease. Finally, 27 pts (32%) received consolidation treatment with high-dose cytarabine after MTX-based CT. For toxicity, among the 351 infusions performed for the 85 pts who received MTX-based CT, grade 3-4 toxicities were: 46% of any events, 15% of infection, 13% of cytopenia, 10.5% of acute renal failure and 8% of elevated liver enzymes. 13% of pts presented toxic death. Median progression free survival (PFS) and overall survival (OS) were 3.9 months and 7 months, respectively. Pts treated with MTX-based CT had a significantly prolonged PFS and OS as compared to patients treated without MTX or with palliative care (Figure 1A, 1B). In the univariate analysis performed for the 85 pts treated with MTX-based CT, no initial clinical and biological characteristics (age, PS, type of symptoms, CIRS-G, tumor localization, LDH level, albumin level, hemoglobin level, lymphocyte count, creatinine clearance) influenced PFS or OS. The initial dose of MTX did not influence outcome but intravenous rituximab used in first line therapy significantly improved PFS and OS (Figure 1C, 1D). Conclusions: to the best of our knowledge, this is the largest series of consecutive PCNSL pts aged of 80y or over prospectively recorded in a national database. This study showed that the prognosis remains poor with major toxicity under conventional treatment. No clinical predictor of survival was highlighted in our series but patients initially treated with MTX-based CT in combination with rituximab had an improved outcome. The development of target and innovative therapies is needed for this category of patients representing 8% of all PCNSL in the database of the LOC network. Disclosures Houot: Celgene: Honoraria; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Novartis: Honoraria.

Description: Extranodal NK/T-cell lymphoma, nasal type, is a rare and highly aggressive disease with a grim prognosis. No therapeutic strategy is currently identified in relapsing patients. We report the results of a French prospective phase II trial of an L-asparaginase-containing regimen in 19 patients with relapsed or refractory disease treated in 13 centers. Eleven patients were in relapse and 8 patients were refractory to their first line of treatment. L-Asparaginase–based treatment yielded objective responses in 14 of the 18 evaluable patients after 3 cycles. Eleven patients entered complete remission (61%), and only 4 of them relapsed. The median overall survival time was 1 year, with a median response duration of 12 months. The main adverse events were hepatitis, cytopenia, and allergy. The absence of antiasparaginase antibodies and the disappearance of Epstein-Barr virus serum DNA were significantly associated with a better outcome. These data confirm the excellent activity of L-asparaginase–containing regimens in extranodal NK/T-cell lymphoma. L-Asparaginase–based treatment should thus be considered for salvage therapy, especially in patients with disseminated disease. First-line L-asparaginase combination therapy for extranodal NK/T-cell lymphoma warrants evaluation in prospective trials. This trial is registered at www.clinicaltrials.gov as #NCT00283985.

Description: Abstract 3872 Poster Board III-808 Introduction POEMS syndrome is a rare disease characterized by peripheral neuropathy, organomegaly, endocrinopathy, monoclonal plasma cells, skin changes, papilledema, volume overload, sclerotic bone lesions, thrombocytosis, and high serum VEGF level. Efficient treatments consist in irradiation for patients with localized solitary plasmocytoma and high-dose chemotherapy with autologous stem cell transplantation for appropriate candidates without a focal lesion. Conventional myeloma chemotherapy can only control the disease in a limited number of patients. Results of monoclonal anti-VEGF antibodies, which seem to be attractive due to the role of VEGF in this disease, are controversy with efficacy in 3 patients but treatment related deaths in 2 other patients. Thalidomide effectiveness has been reported in Japanese patients but enthusiasm for its use is tempered by the high incidence of thalidomide-induced peripheral neuropathy. Lenalidomide, which efficacy has been described in one observation (Dispenzieri, Blood 2007 110: 1075-1076), has the advantage of being anti-angiogenic, cytotoxic to malignant plasma cells and with a much lower risk of peripheral neuropathy. We reported here a multicentric French experience with this drug in POEMS syndrome. Patients and Methods There were 3 women and 6 men treated with Lenalidomide in 7 French centres. Median age was 60 (41-76). All patients had sensitive polyneuropathy with motor deficiency in 5 patients. A monoclonal component was present in all cases (IgA lambda in 7 patients, IgG lambda and lambda light chain only in 1 patient each). Other manifestations of POEMS syndrome included sclerotic bone lesions in 6 patients, endocrinopathies in 7 patients, skin changes in 8 patients, oedema in 7 patients, organomegaly in 5 patients, papilledema in 5 patients, thrombocytosis in 3 patients. VEGF serum level was elevated in 4 among 5 patients with a dosage. Previous treatments were high-dose chemotherapy with autologous stem cell transplantation in 3 patients, Melphalan-Prednisone in 3 patients because of advanced age, and prolonged steroid treatment in 2 patients. One patient received Lenalidomide as primary treatment before high-dose therapy. Lenalidomide was given during 21 days each month and sequentially associated with dexamethasone, 5 patients received 25 mg/day and 4 patients received 10 or 15 mg, for a median of 5 cycles (1 to 11). Results Serious side effects were noted in 3 patients with 2 hematologic toxicities (grade III and IV) and a cutaneous allergy. Six patients could be evaluated for hematologic response and all responded, complete response in 3 patients and partial in 3 (〉25%). Clinical responses occurred early, before 3 months of treatment, in 6 cases among 8 (1 patient is not yet evaluable), with a marked improvement in performance and in neurological syndrome. Other manifestations of POEMS syndrome improved, especially oedema in 5 cases among 6. VEGF level (normal value 〈 500 pg/ml) could be serially measured in 4 patients with a normalization in 1 patient and a significant decrease in 3 patients, median 7100 pg/ml (2100-10100) before treatment to 887 pg/ml (304-3270). In 1 of these 3 patients VEGF level increased to initial value while he was still taking Lenalidomide. A second patient experimented a relapse 5 months after ending Lenalidomide, he is still in good response after Lenalidomide reintroduction. With a median follow-up of 12 months (1-26) all patients are alive. Conclusion Lenalidomide seems to be a very promising therapy in POEMS syndrome. It should be tested in larger studies in patients with a systemic disease, who are not able to receive high dose therapy, in relapsing patients and before high dose treatment to avoid transplant related morbidity, particularly engraftment syndrome. Disclosures: Jaccard: Celgene: Membership on an entity's Board of Directors or advisory committees. Facon:Celgene: Membership on an entity's Board of Directors or advisory committees and Speakers Bureau. Moreau:Celgene: Membership on an entity's Board of Directors or advisory committees. Fermand:Celgene: Speakers Bureau.

Description: Abstract 1344 In September 2007 we published the results of a prospective randomized trial comparing in 100 AL amyloidosis patients, enrolled between January 2000 and January 2005, high dose melphalan with ASCT and the oral regimen M-Dex (melphalan 10 mg per square meter of body-surface area and dexamethasone 40 mg per day, on days 1 to 4). With a median follow-up of 3 years the median survival was better in the M-Dex arm (56.9 months) than in the ASCT arm (22.2) months (p=0.04). The hematological responses were not statistically different between the 2 arms and the higher toxicity of the ASCT arm was responsible for the shorter median survival. This study has been criticised because of the high treatment related mortality (TRM) in the ASCT arm but a landmark analysis of patients who survived for at least 6 months and who received their assigned treatment, did not show any difference in survival. A second frequent criticism was that too severe patients, who were not able to go through the high dose procedure, have been included. A separate analysis done within the 59 good risk patients showed a nonsignificant difference between the two groups in overall survival at 3 years (58% in the group assigned to receive ASCT vs. 80% in the group assigned to receive M-Dex; P = 0.13). A third concern was related to the duration of response, should high dose treatment, giving slightly more complete responses, results in more sustained responses and, with a prolonged follow-up, in a better long term survival ? To answer this question we extended the follow-up of the surviving patients. The new cut off date was August 1st, 2010, more than 5 and a half years after the last inclusion. Only 1 patient has been lost to follow-up. We did again the landmark analysis with the longer follow-up and we looked, in this population of 65 patients with 100% feasibility and 0 % TRM, at survival and remission duration. As the follow-up was very long and the biologic surveillance not planned after 2006 we took unequivocal events as censor points for the event-free survival analysis: deaths and second line treatment. At the first cutoff date, in 2006, 49 patients were alive, 30 in the M-Dex arm and 19 in the HDT arm. At the new cutoff date in 2010, 38 patients are alive, 22 in the M-Dex arm and 16 in the intensive arm, with a median follow-up of 49 months for the entire cohort and 86 months for surviving patients (figure 1). The majority of late deaths were amyloid related, but 3 patients in the M-Dex arm died of unrelated lung and digestive cancer. The median survival in the 2 arms has not been modified (56.9 month in the M-Dex arm and 22.2 month in ASCT arm, p=0.15). For the 65 patients included in the landmark analysis the median survival is not different in the 2 arms (103 month in the M-Dex arm and 97 month in ASCT arm) and the median event free survival is 56 months in the M-Dex arm and 26 months in the intensive arm (p=0.3, figure 2). Eleven surviving patients in the M-Dex arm and 6 in the intensive have not received a second treatment, 9 of these patients in the M-Dex arm and 5 in the ASCT arm have normal free light chain measurement at their last visit. Only 1 patient, assigned to receive ASCT, has been diagnosed with myelodysplasia. With a longer follow-up we did not found any superiority in the intensive arm in survival or remission duration even in the landmark analysis eliminating treatment related mortality. In the area of very efficient new drugs this analysis reinforces our choice to propose conventional treatment to amyloidosis patient avoiding the risk of intensive treatment.Figure 1.Survival according to treatment groupFigure 1. Survival according to treatment groupFigure 2.Event-Free Survival According to Treatment Group in the Landmark AnalysisFigure 2. Event-Free Survival According to Treatment Group in the Landmark Analysis Disclosures: Leblond: roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; mundipharma: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; genzyme: Membership on an entity's Board of Directors or advisory committees; celgene: Membership on an entity's Board of Directors or advisory committees; jansen: Membership on an entity's Board of Directors or advisory committees. Leleu:Celgene: Consultancy, Research Funding; Janssen Cilag: Consultancy, Research Funding; Leo Pharma: Consultancy; Amgen: Consultancy; Chugai: Research Funding; Roche: Consultancy, Research Funding; Novartis: Consultancy, Research Funding.

Description: It is important to have an effective therapy for patients with multiple myeloma (MM) at first relapse, particularly if an autologous stem cell transplant (ASCT) is considered at this stage. This multicenter, phase 2 trial evaluated the efficacy and safety of weekly oral pomalidomide-cyclophosphamide-dexamethasone (PCD) in patients with MM in first relapse after treatment with lenalidomide-bortezomib-dexamethasone (RVD). All patients had received RVD as induction and consolidation therapy, plus lenalidomide maintenance for 1 year (arm A). Half had also received an ASCT after induction (arm B). At MM relapse, all patients received 4 oral cycles of pomalidomide 4 mg (days 1-21), cyclophosphamide 300 mg (days 1, 8, 15, and 22), and dexamethasone 40 mg (days 1-4 and days 15-18 of a 28-day cycle; PCD). Responding patients in arm A underwent ASCT and received 2 additional cycles of PCD, whereas those in arm B received 5 cycles of PCD. All patients received pomalidomide-dexamethasone maintenance until disease progression. Primary end point was partial remission or better after the initial 4 cycles of PCD. Responses were obtained in 82/97 (85%) patients evaluated: complete remission (n = 1; 1%), very good partial remission (n = 32; 33%), and partial remission (n = 49; 51%). Three patients (3%) had stable disease, and 6 (6%) had disease progression (6 response failures). Forty-five (94%) of the 48 patients in arm A underwent planned ASCT. PCD was effective therapy after first relapse with RVD. After 4 cycles, the rate of partial remission or better was 85%, and 94% of planned ASCTs were performed. Toxicity was mostly hematologic and manageable. This trial was registered at www.clinicaltrials.gov as #NCT02244125.