ALBERT

Description: Abstract 1223 Poster Board I-245 Introduction This study aimed at evaluating the impact of three different pre-transplant therapies on the outcome of patients (pts) eligible for high-dose therapy. Methods two-hundred sixty eight newly diagnosed MM pts aged £65 years, Durie-Salmon stage III, II, or I in progression, were consecutively enrolled from 2000 to 2007 in three different protocols, with three different pre-transplant therapy: Group 1: (145 pts) 3 pulse-VAD cycles; Group 2: (67 pts) 3 pulse-VAD cycles plus 3 Thal-Dex cycles (thalidomide at the dose of 100 mg/day orally at bedtime, continuously for 3 months, oral dexamethasone at the dose of 20 mg on days 1-4 and 14-17 every 28 days); Group 3: (57pts) 4 Vel-Dex courses (Bortezomib 1.3 mg/m2 i.v. on days 1, 4, 8, 11; oral Dexamethasone 40 mg on days 1-4 and 8-11 every 3 weeks). After induction all pts received two DCEP-short cycles as mobilization (oral Dexamethasone 40 mg/day on days 1-4 + Cyclophosphamide 700 mg/m2/day i.v., Etoposide 100 mg/ m2/day i.v., cisPlatin 25 mg/m2/day for 2 days) with peripheral blood stem-cell (PBSC) collection prompted by G-CSF followed by one or two transplants (Tx) with melphalan 200 mg/m2 as conditioning regimen. Response was defined according to IMWG uniform criteria. Pts were considered responsive when obtaining at least a PR. Results pts in the three group were similar for age, gender, Ig type, ISS stage. A significant higher percentage of Durie and Salmon stages III was found in group 3 (83% vs 68% in group 1 and 67% in group 2, p=0.0002). The median follow-up was 46 (1-150) months for group 1, 43 (1-68) months for group 2, and 29.7 (1-79) months for group 3. At the time of this analysis in the three groups 51%, 65%, 90% of transplanted pts respectively were still alive, and progression after transplant was registered in 84%, 80%, 50% respectively. Patient flow before Tx was similar (p=0.45): 19% in group 1, 27% in group 2, 23% in group 3. In group 1, 2% of pts went off-study after VAD, and 17% after mobilization phase. In group 2, patient flow was equally distributed: 7% after pulse VAD, 10% after thal-dex, 9% after DCEP. In group 3, 12% of the pts went off-study after Vel-Dex, 11% after DCEP. Table 1 summarized responses. In group 3 (Vel-Dex) response was better along all protocol phases with respect to group 1 or 2 (p

Description: Bakground. The association of light chain (AL) amyloidosis with lymphoplasmacytic lymphoma/Waldenström's Macroglobulinemia is well established. However, both localized and systemic AL amyloidosis have been also reported in other types of lymphoma, but a detailed description of these cases is still lacking. Methods. We systematically searched the database of 1,415 newly diagnosed consecutive patients (pts) with AL amyloidosis of the Pavia Amyloidosis Research and Treatment Center for pts with non-lymphoplasmacytic lymphoma and AL amyloidosis, and identified 34 pts diagnosed between 2004 and 2018. Results. Seventeen pts (50%) had a diagnosis of marginal zone lymphoma (MZL), mainly extranodal MZL (EMZL). Median age at the time of lymphoma diagnosis was 65 years (45-81) and 23 pts (68%) were males. An autoimmune disease was documented in 8 pts (24%), with Sjögren Syndrome as the commonest type. Clinical characteristics of pts according to type of lymphoma (MZL vs non-MZL) and type of AL (systemic vs localized) are presented in Tables 1 and 2. The amyloid deposits were characterized as AL-type by immunoelectron microscopy or mass spectrometry in all cases. Twelve pts (35%) had a concomitant diagnosis of AL (within 12 months before or after the diagnosis of lymphoma). In 2 cases the diagnosis of lymphoma occurred after 16 and 45 months from diagnosis of AL, respectively. In 20 pts (10 MZLs), the lymphoma was diagnosed a median time of 58.6 months (range: 13.6-320.8 months) before AL diagnosis: all but 1 of these cases were treated for the underlying lymphoma and 16 of them had a complete remission at the time of AL diagnosis. Twenty-nine pts (85%) had positive serum and/or urine immunofixation and/or an abnormal free light chains ratio (FLCR), while 5 pts had no detectable monoclonal component (MC) and normal FLCR: these pts developed only localized AL amyloidosis. Localized AL was documented in 10 pts (29%), 7 of them had a MZL. Involved organs were represented by MALT sites (6 nodular pulmonary, 1 tracheobronchial, 2 skin, 1 bladder). Eleven pts with systemic AL amyloidosis died for progression of amyloidosis and 1 because of gastric cancer, while no patient with localized AL died during follow-up. The median overall survival (OS) from the diagnosis of AL amyloidosis was 42.5 months (Fig.1). Conclusions. In our series collected in a referral center, MZL is the most common non-lymphoplasmacytic lymphoma that associates with AL amyloidosis. Hematologists should be aware that MZL is associated not only with localized light chain deposition at the lymphoma site, but also with systemic AL amyloidosis. Systemic AL amyloidosis could be itself an indication to start a specific treatment for the lymphoproliferative disease, even in otherwise asymptomatic lymphomas. The presence of a MC and elevated FLC are clues for systemic AL amyloidosis. Figure 1. Figure 1. Disclosures Merlini: Prothena: Consultancy; Janssen: Consultancy; Ionis: Consultancy; Millenium: Consultancy; Akcea: Consultancy; Pfizer: Consultancy. Palladini:Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Other: Travel support; Prothena: Honoraria.

Description: Abstract 2957 Fotemustine (Muphoran), a nitrosourea alkylating agent approved for metastatic melanoma, and recently used in alternative autotransplant condition regimen (FEAM) for lymphoma patients, has proven to be active as single agent in Multiple Myeloma (MM) refractory-relapsed patients. Given the importance of reaching high-quality response even beyond frontline setting, and the proven activity of the proteasome inhibitor bortezomib + dexamethasone therapy, we explored by means of a phase I-II dose escalation study the feasibility and the efficacy of the three drug combination bortezomib (B) + fotemustine (Mu) + dexamethasone (D) (B-MuD) in MM patients (pts) relapsed after at least one therapy. The study has been approved by our local ethical committee; all pts signed written informed consent. Fotemustine was administered at two dose levels (80–100 mg/m2 i.v.) on day 1. The original 21-day schedule was early amended due to extra-hematological toxicity and a 35-day schedule was adopted (Bortezomib 1,3 mg/ m2 i.v. on days 1, 8, 15, 22, Dexamethasone 20 mg i.v. on days 1, 8, 15, 22) for a total of six courses. Twenty-four pts have been enrolled: M/F 13 (54%)/11(46%), median age 69 years (44–83), median number of previous therapies 2 (1–5). Previous treatments included autologous transplant in 13 pts (54%), bortezomib in 8 pts (33%), oral melphalan in 11 pts (46%) and thalidomide in 15 (63%). The MTD of Fotemustine was tested to be 100 mg/m2. Six pts dropped-out: 4 pts for extra-hematological toxicity, 2 for progression. The overall response rate was of 62% (CR 8%, VGPR 33%, PR 21%). Median time to first response was 36 days (range 21–83) with a median DOR of 19.4 months (95% CI 11.6–23.7 months). After a median follow-up of 24.3 months (range 1.6–32.8 months), the median OS was 28.5 months (95% CI 22.1-NR). The median TTP and the median PFS were 20.5 (95% CI 11.9–22.2 months) and 19.1 (95% CI 11.9–22.2) months respectively. Median time to next therapy (TNT) was 16.2 months (4–25.2). There was a correlation between response and PFS (p=0.0002). B-MuD resulted effective in patients previous exposed to bortezomib without difference in terms of response (p=0.25) and PFS (p=0.87) when compared to bortezomib-naive patients. As far as toxicity was concern, one-hundred and thirty-three AE of any grade were observed, 65 hematological (49%) and 68 (51%) non-hematological; Thrombocytopenia was the most common AE (32%) overall. Extra-hematological toxicity included neuropathy (23%), infections (14%), gastrointestinal symptoms (7%). Half of the events occurred during the first two cycles (49%), most were manageable, with 69% resolved or improved, 15% unchanged, 15% worsened. In conclusion B-MuD is effective and well tolerated in relapsed MM even in patients in advanced phase and previously exposed to several lines of therapies, including bortezomib. Disclosures: No relevant conflicts of interest to declare.

Description: BACKGROUND As lenalidomide (LEN) becomes increasingly established as a standard of care in the treatment (Tx) of newly diagnosed multiple myeloma (NDMM), patients (pts) for whom LEN is no longer a Tx option, including those who have become refractory to LEN, represent a clinical reality. These pts represent the largest population with MM at first relapse in the United States and a growing population globally. To date, they have been poorly studied and remain difficult to treat. Previous trials have demonstrated a clinical benefit with pomalidomide (POM) therapy in LEN-refractory pts with relapsed or refractory MM (RRMM), including those who were heavily pretreated (median of 5 prior regimens) (San Miguel et al. Lancet Oncol 2013; Richardson et al. Blood 2014; Dimopoulos et al. Blood 2016). These studies led to the approval of POM + low-dose dexamethasone (LoDEX) in RRMM. The pomalidomide, bortezomib, and low-dose dexamethasone (PVd) regimen has shown promising activity in early-phase clinical trials in LEN-refractory pts. In the phase 3 OPTIMISMM trial, PVd showed significantly improved progression-free survival (PFS) and a manageable safety profile compared with bortezomib and low-dose dexamethasone (Vd) in intent-to-treat population of pts who received 1-3 prior regimens and were 100% LEN pretreated; 70% of pts were LEN refractory (Richardson et al. ASCO 2018 abstract 8001). Here, we present efficacy and safety results in LEN-refractory and -nonrefractory pts treated at first relapse. METHODS Pts were randomized 1:1 to receive PVd or Vd in 21-day cycles: POM 4 mg/day on days 1-14 (PVd arm only); bortezomib (BORT) 1.3 mg/m2 on days 1, 4, 8, and 11 of cycles 1-8 and on days 1 and 8 of cycles 9+; and DEX 20 mg/day (10 mg/day if aged 〉 75 yrs) on the days of and after BORT. Key eligibility criteria included ≥ 2 cycles of prior LEN therapy, including LEN-refractory pts. BORT-exposed pts were eligible to enroll, provided they did not have progressive disease during therapy or within 60 days of the last dose of a BORT-containing regimen with BORT dosed at 1.3 mg/m2 twice weekly. The primary endpoint was PFS. RESULTS Out of 559 pts enrolled patients, 226 were treated in the second line (2L), data cut off October 26, 2017: 111 with PVd and 115 with Vd. Median follow-up for 2L pts was 16.4 mos. Among 2L pts, 129 (57.1%) were LEN refractory (64 PVd; 65 Vd) and 97 (42.9%) were LEN nonrefractory (47 PVd; 50 Vd). In LEN-refractory pts (PVd vs Vd) median age was 68.0 vs 69.0 yrs, 57.8% vs 58.5% were male, and 56.3% vs 47.7% had prior BORT. In LEN-nonrefractory pts, median age was 66.0 vs 65.5 yrs, 63.8% vs 38% were male, and 66.0% vs 72.0% had prior BORT. Other key baseline characteristics were similar between Tx arms and subgroups. Median PFS was 17.8 mos with PVd vs 9.5 mos with Vd in LEN-refractory (HR 0.55; 95% CI, 0.33-0.94; Figure 1A) and 22.0 vs 12.0 mos in LEN-nonrefractory pts (HR 0.54; 95% CI, 0.29-1.01; Figure 1B). Response outcomes are shown in Figure 2. ORR was 85.9% with PVd vs 50.8% with Vd in LEN-refractory pts (P 〈 .001) and 95.7% vs 60.0% in LEN-nonrefractory pts (P 〈 .001). In 2L LEN-refractory pts, the most common grade 3 or 4 treatment-emergent adverse events (TEAEs) with PVd vs Vd were neutropenia (35.9% vs 12.9%), thrombocytopenia (17.2% vs 22.6%), and anemia (17.2% vs 8.1%). Grade 3 or 4 infections occurred in 29.7% vs 21.0% of pts. In 2L LEN-nonrefractory pts, the most common grade 3 or 4 TEAEs were neutropenia (36.2% vs 6.3%) and thrombocytopenia (23.4% vs 18.8%). Grade 3 or 4 infections occurred in 27.7% vs 8.3% of pts. In 2L LEN-refractory pts, median Tx duration of PVd vs Vd was 9.7 vs 6.1 mos. In 2L LEN-nonrefractory pts, median Tx duration of Pvd vs Vd was 13.6 vs 6.6 mos. CONCLUSIONS To date, OPTIMISMM is the only phase 3 trial to address Tx of pts with RRMM following LEN exposure in early lines and the first to report data in LEN-refractory pts after first relapse. PVd reduced the risk of progression and death by 45% and 46% vs Vd in LEN-refractory and -nonrefractory pts, respectively. Further, in both subgroups, 2L Tx with PVd significantly improved ORR and led to deeper responses compared with Vd. AEs with PVd therapy were generally consistent with the known AEs of POM, BORT, and DEX. These data further demonstrate that PVd is effective and tolerable in pts for whom LEN is no longer a Tx option, including LEN-refractory pts, supporting its use as 2L therapy in RRMM. Disclosures Dimopoulos: Celgene: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Takeda: Honoraria; Bristol-Myers Squibb: Honoraria. Weisel:Amgen, Celgene, Janssen, and Sanofi: Research Funding; Amgen, BMS, Celgene, Janssen, and Takeda: Honoraria; Amgen, BMS, Celgene, Janssen, Juno, Sanofi, and Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees. Moreau:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Anderson:Celgene: Speakers Bureau; Amgen: Speakers Bureau; Takeda: Speakers Bureau. White:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. San-Miguel:Celgene: Honoraria; Janssen: Honoraria; Sanofi: Honoraria; Amgen: Honoraria; Roche: Honoraria; BMS: Honoraria; Novartis: Honoraria. Sonneveld:Amgen: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Karyopharm: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding. Jenner:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Chugai: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau. Dürig:Janssen: Consultancy, Honoraria; Celgene: Honoraria; Roche: Honoraria, Speakers Bureau. Pavic:AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Salomo:Cilag: Consultancy; Janssen: Consultancy. Yu:Celgene: Employment, Equity Ownership. Nguyen:Celgene Corporation: Employment. Bensmaine:Celgene: Equity Ownership. Peluso:Celgene Corporation: Employment, Equity Ownership. Zaki:Celgene Corporation: Employment, Equity Ownership. Richardson:BMS: Research Funding; Karyopharm: 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, Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: 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; Amgen: Membership on an entity's Board of Directors or advisory committees.

Description: Key Points Using a sensitive method, the MYD88 (L265P) mutation is detectable in all patients with Waldenström’s macroglobulinemia, therefore representing a hallmark of the disease. MYD88 (L265P) is also found in a substantial proportion of patients with IgM-MGUS.

Description: Key PointsAmyloidogenic PCs show unique PI susceptibility and altered organelle homeostasis, consistent with defective autophagy. Amyloidogenic LC production is an intrinsic cellular stressor that sensitizes to PI toxicity.

Description: Extramedullary myeloma (EMM) at diagnosis or during the course of the disease is rare and often anecdotal. We reviewed the records of 965 consecutive MM pts diagnosed and followed from 1969 to July 2007 in order to evaluate: the overall incidence of EMMs and the changes over time clinical presentation, response to treatment and outcome of EMM pts divided into two subgroups according to the time of appearance, at diagnosis or during the course of the disease. We considered three periods: 1969–1989 (conventional chemotherapy, CCT); 1990–1999 (introduction of high-dose therapy, HDT); 2000–2007, (era of novel agents). The overall incidence of EMM was of 13% (129/965 pts), 87/42 M/F, median age 58 (31–80) years. A prior MGUS was present in 24 pts and a solitary plasmacytoma in 10 (8%). Characteristics at the time of EMM were: 77 pts IgG (60%), 23 IgA (18%), 2 IgM (2%), 16 light chain (12%), 11 not secretory (8%); 29 pts were in stage I, 14 in stage II, 86 in stage III; 30/129 pts (23%) were asymptomatic. More frequently involved sites were: paravertebral (40%), rib cage (32%), pelvis (10%). Multiple localizations were present in 27 pts (21%). A plasmacytic leukemia was observed during the follow-up in 9 pts (7%). The overall median follow-up was 24.4 (2.5–148) months. Seventy-three pts presented EMM at the time of diagnosis with different incidences in the 3 periods: 1969–1989 4.5%, 1990–99 4.3%, 2000–07 12.7%. These pts were treated with HDT in 43 cases (59%) and CCT in 30 (41%). Radiotherapy (RT) was associated in 38 pts (52%). A partial response (PR) was achieved in 49 pts (67%). Progression or relapse were observed in 46 pts (63%) and the median time to progression (TTP) and overall survival (OS) in this subgroup of pts were 17.3 and 21.5 months respectively. The other 56 pts showed an EMM during the course of the disease after a median time of 20 (2–144) months from diagnosis. EMM incidence varied as follows: 1969–1989 2.7%, 1990–99 7.2%, 2000–07 7.4%. Median number of previous lines of therapy was 1 (range: 1–7), including HDT in 22 pts (39%), thalidomide or lenalidomide in 18 (32%), bortezomib in 5 (9%). The median time from HDT to EMM was 17 (2–125) months. Treatment of these pts consisted of CCT in 36 cases (64%), thalidomide in 3 (5%) and bortezomib in 8 (14%). RT was given in 29 cases (52%). Response rate in this subgroup was low, only 30% of pts obtained a PR. The median TTP and OS from the time of appearance of EMM were 4.7 and 6.5 months respectively and the overall survival from the diagnosis was 29.9 months. The two groups of EMM pts were also compared for all the clinical characteristics, response to therapy and outcome. EMM pts at diagnosis showed higher levels of monoclonal component and haemoglobin, and lower bone marrow plasmacytosis with respect to the others. OS from diagnosis was similar in the two groups. In conclusion, our study shows an increased incidence of EMM over time. The more recent increase of EMM at diagnosis might be due to the wider use of more sensitive imaging techniques as CT scan and magnetic resonance, while during the course of the disease after 1990 could be related to the longer survival of pts thanks to the new therapeutic approaches. Anyway, the presence of EMM whether at diagnosis or at progression seems to negatively affect the outcome of pts since the OS is shorter than MM pts without EMM.

Description: Abstract 4003 Skeletal related events (SREs) are a significant cause of morbidity and mortality in multiple myeloma (MM). Markers of bone turn-over, in particular serum C-terminal telopeptide of type I collagen (CTX), can be used for monitoring early signs of bone damage either in osteoporosis or in neoplasm such as Multiple Myeloma. Since serum CTX levels are significantly decreased during bisphosphonate treatments (Dennis, N Engl J Med 2008), it is not clear whether serum CTX monitoring still retain a role in predicting SREs once bisphosphonate treatments was started. Aim of this study was to test whether serum CTX monitoring significantly correlates with active bone disease in a population of MM patients irrespective of concomitant bisphosphonate treatment. An unselected cohort of 87 patients with multiple myeloma diagnosed at our Hematology Division with the following characteristics entered this study: the availability of a baseline determination of serum CTX prior to start bisphosphonate therapy, multiple sequential serum CTX determinations (≥2 performed with an interval of at least 4 weeks), a radiologic evaluation available at the time of any SREs. The study was approved by our local ethical committee and conducted according to Helsinki Declaration guidelines. Patients baseline characteristics were the following: M/F 59%/41%, median age 60 (range 37–86), Durie and Salmon stage I/II/III (11%/14%/75%). During the study period (median follow-up 2.8 year, range 0.4–21 years), 73 patients (83%) experienced at least one SRE. Development of SRE was evaluated by standard skeletal x-ray, CT or MRI scan. Serum CTX was measured by an enzyme chemiluminescence method. A total of 260 serum CTX determinations were available for statistical analysis (median number of determinations for each patient 3, range 2–9). Univariate analysis found a statistically significant association between serum CTX and bone disease status with higher values in patients with active lytic lesions when compared to patients without radiological evidence of bone disease (median value 0.411 vs 0.356, p

Description: Introduction. The incidence of multiple myeloma (MM) is increasing in particular due to the aging of the population.In the last 15 years, stem cell transplantation and novel agents have increased the remission rates and improved survival. The aim of the present work is to assess the epidemiologic burden of treated patients from population-based data. Methods. The Regional Health Service (RHS) of Lombardy covers around 10 million people. Administrative datasets available within the Lombardy RHS included: demographic data, hospital discharges, pharmaceutical prescriptions, and outpatient claims. Since 2000 these archives were organized into a data warehouse named DENALI. A distinguishing feature of DENALI is the probabilistic reconstruction of links to match the data of different datasets belonging to the same person. The initial study population was selected from DENALI and involved all those individuals who during the period 2003-2009 had at least one hospital discharge for MM and at least one MM specific drug prescription among melphalan, bortezomib, cyclophosphamide, thalidomide, doxorubicin, and lenalidomide. The first hospital discharge or drug prescription date whichever occurred first was identified as the index date. From the initial population we excluded individuals with a diagnosis of cancer prior to the index date to avoid overlapping oncological diagnoses, and also those who did not receive chemotherapy (CHT) to focus on patients with symptomatic MM. The study population was followed up until 31-Dec-2010 or death. We evaluated clinical and demographic characteristics, incidence and mortality of the selected MM patients.Age was estimated at the index event and reported in years with corresponding minimum and maximum range. Comorbidity conditions were synthetized by Charlson Comorbidity Index (CCI) on diagnoses of hospital discharges occurred before the index date. Crude incidence was estimated with respect of Lombardy inhabitants and expressed x100,000 of them, as the corresponding 95% Confidence Intervals (95%C.I.). Age-adjusted incidence was estimated using the 2001 standard population proposed by the World Health Organization (WHO). Relative survival ratios (RSRs) were computed as measure of survival. Results. A total of 3,043 eligible subjects was identified (52% male). Median age(min-max) at the index date was 67.4 (26.9-92.3) years in male and 69.8 (17.5-96.8) in female patients. CCI showed high comorbidity component (CCI〉=2) in 10% and 6% of male and female individuals, respectively. Crude incidence and mortality rates were reported in Figure 1 and Figure 2. Crude and age standardized incidence was respectively 4.9 and 3.7 for males and 4.4 and 2.7 for females. Crude and age standardized mortality rates were respectively 2.2 and 1.6 for males and 2.0 and 1.1 for females. Within the study population, 1- and 5-year RSRs (95% C.I.) were 85%(83-86%) and 49%(46-51%), respectively, with no significant differences between genders. Thirty-seven percent of the study population had at least one prescription of the novel agents for MM (bortezomib, lenalidomide, and thalidomide). Thirty percent of the study population had a Stem Cell Transplantation (SCT): they had a median age(min-max) of 60.2(21.7-75.4), low comorbidity score(CCI=0) in 90% of them and 1- and 5-year RSRs equal to 98%(97-99%) and 70%(66-74%), respectively. Seventy percent of the study population received CHT but not SCT: their median age(min-max) was 72.6(17.5-96.8), 74% of them had CCI=0 and 1- and 5-year RSRs equal to 78%(76-80%) and 39%(35-41%), respectively. Treated but not transplanted patients have been estimated to experience a significant (p

Description: Introduction. In the last 15 years, stem cell transplantation and novel agents have increased the remission rates and improved survival in multiple myeloma (MM) but they have also affected the cost of myeloma treatment. The aim of the present study was to describe direct healthcare costs in treating MM patients from a 2003-2009 population-based study. Methods. Since 2000the Regional Health Service (RHS) of Lombardy, covering around 10 million people, systematically organizes its healthcare administrative archives into a data warehouse named DENALI. A distinguishing feature of DENALI is the probabilistic reconstruction of links to match the data of different datasets belonging to the same person. The study population of the present study was selected from DENALI and involved all those individuals who during the period 2003-2009 had at least one hospital discharge for MM and at least one MM specific drug prescription among melphalan, bortezomib, cyclophosphamide, thalidomide, doxorubicin, and lenalidomide. The index date was identified by the first hospital discharge or drug prescription whichever occurred first. From the initial population we excluded individuals with a diagnosis of cancer prior to the index date to avoid overlapping oncological diagnoses, and also those who did not receive chemotherapy (CHT) to focus on patients with symptomatic MM. The period of observation ended at 31-Dec-2010. The study period was divided in one year before the index event (given by 365 days before the index date) and 8 follow-up (FU) years (ranging from 1 to 8 years after the index date, the latter included in the first follow-up year). We estimated healthcare costs (hospitalizations, drugs and outpatient examinations/visits) per patient per year from the RHSÕs perspective. Costs were expressed in euro. Results. During the study period, a total of 3,043 eligible subjects (52% male) experienced at least one hospital admission for MM and one prescription of MM specific drug, corresponding to 4.6 cases on 100,000 Lombardy inhabitants per year. Subjects had a median (min-max) age of 68.6 (17.5-96.8) years. Patient who had a Stem Cell Transplantation (SCT) represented 30% of the study population: within this group 90% had one or more Autologous Stem Cell Transplantation (ASCT), 1.5% had one or more Allogenic Stem Cell Transplantation and the remaining 8.4% had both. The average cost for a treated MM patient during the 8 years of study period was 64,816 (95% I.C. 62,628-67,003). In the year of index (FU1) the average cost was 31,945 (95% I.C. 30,776-33,113): 75% represented by hospitalizations, 18% by drug prescriptions and 7% by outpatients. A patient who had at least one SCT reported an average cost of 125,202 (120,777-129,628) during the entire follow-up period: 66,068 (63,820-68,314) in the year of index with a distribution by type of cost of 85%,10%, and 5% represented by hospitalizations, drug prescriptions and outpatients, respectively. Accordingly, patients treated with only pharmacological treatment (CHT) had a 8 years average cost equal to 38,433 (37,097-39,788): 17,042 (16,477-17,606) during the year of index with hospitalizations as the main cost driver (58%), followed by drug prescriptions (32%) and outpatients (10%). The distribution of the average cost by year of observation and cost type was shown in Figure 1. Within the SCT patients who had one ore more ASCT the mean cost was 114,661 (110,801-118,521) in the year of index (FU1) while for those who had one or more allogenic SCT the mean cost was 171,779 (132,925-210,634). During the year of index those CHT patients older than 76 years had a mean cost equal to 14,589 (13,794-15,384) significantly (p