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Higher cumulative dose of bortezomib, a key component of Multiple Myeloma (MM) treatment regimens, has been shown to improve outcomes in MM patients, but must be balanced with toxicities including peripheral neuropathy. In this study, we studied the effect of cumulative bortezomib dose on survival, depth of response, and discontinuation rate in transplant ineligible MM patients.Data from 70 patients treated with Cyclophsophamide, Bortezomib, and Dexamethasone (CyBorD) in a single Canadian center were grouped according to above vs below median cumulative bortezomib dose and analyzed for progression-free survival (PFS), overall survival (OS), depth of response, and discontinuation rate.There was a trend for lower discontinuation rate (45.7% vs. 68.6%, P = .052) and significantly lower rate of neuropathy-related discontinuation (5.7% vs. 22.9%, P = .035) in patients who received higher than 43.1 mg/m² of bortezomib. The higher-dose group showed a trend for higher rate of complete response (14.3% vs. 5.7%, P = .225) and significantly higher rate of very good partial response or better (77.1% vs. 51.4%, P = .024). There was significantly longer PFS (24.3 vs. 9.1 months, P = .012) and a trend for longer OS (22.4 vs. 61.3 months, P = .061) in the higher-dose group. In landmark analysis after 180 days, PFS (23.5 vs. 24.3 months, P = .941) and OS were similar in both groups.Higher cumulative bortezomib dose showed a lower rate of discontinuation, longer survival, and deeper response. Determining risk of treatment intolerance remains important for treatment.

Background Amyloid light-chain (AL) amyloidosis is a rare disease with poor survival and significant morbidity. Limited information on the treatment patterns, healthcare resource utilization (HCRU) and clinical outcomes of Canadian AL amyloidosis patients is currently available. This study analyzed existing administrative claims data to better understand this patient population in the real-world setting. Methods Population-based administrative databases in Alberta, Canada were queried from 2010 to 2019 using a claims-based algorithm to identify potential cases of systemic AL amyloidosis. The medical charts of individuals flagged by the algorithm were subsequently reviewed by a trained clinician to confirm the diagnosis. Baseline characteristics, sequencing of pharmacologic therapies, overall survival (OS), and HCRU were evaluated. Individuals with AL amyloidosis were matched 1:4 with members of the general population based on age and sex. The mean difference in number of healthcare touch points was then estimated. HCRU was assessed starting from the time of diagnosis for individuals with AL amyloidosis and starting from the date of first encounter with the healthcare system within the corresponding calendar year for matched members of the general population. Robust variance estimation was used to address clustering due to matching. Results A total of 215 patients were confirmed to have AL amyloidosis. At baseline, the mean age at diagnosis was 66 years (range: 25 to 93 years). The majority of patients were men (59.5%), had an Eastern Cooperative Oncology Group (ECOG) performance status between 0-1 (60.9%), and had at least one comorbidity (84.7%). Approximately 1 in 3 patients had a concurrent multiple myeloma diagnosis. Renal and cardiac involvement were more common at baseline (67.9% and 55.8%, respectively) than liver involvement (15.3%). CyBorD was given to 66.4% of patients who initiated pharmacologic therapy, while most of the remaining 33.6% of patients received another bortezomib-based combination therapy. The most common 2L therapy was the combination of lenalidomide and dexamethasone which was given to 29.9% of individuals who initiated 2L. Median OS from initiation of 1L was markedly improved in patients diagnosed between 2012-2019 compared to 2010-2011 (63.4 vs. 34.5 months, respectively; log-rank p=0.07). Relative to age-sex matched members of the general population, individuals with AL amyloidosis had 118.7 more encounters with the healthcare system within the follow-up period (robust 95% CI: 79.4 to 157.9). Conclusions Since 2012, CyBorD has been the standard of care for Canadian AL amyloidosis patients. While survival has increased over time, 5-year survival remains low which highlights an unmet need for more effective therapies. Relative to the general population, individuals with AL amyloidosis had significantly higher HCRU, underscoring the high disease burden.

Background The proteasome is an exciting target for the development of novel anticancer therapies. Recent evidence has suggested that bortezomib, a dipeptide boronate proteasome inhibitor, exhibits unprecedented single-agent activity in amyloid light chain (AL) amyloidosis. Patients and Methods We performed a retrospective review of the use of bortezomib-containing regimens to assess the rapidity and quality of response at our institution. Results A total of 52 patients with documented newly diagnosed and relapsed AL amyloidosis treated with bortezomib-containing regimens were identified from our institutional database. After a median of 4 cycles (range, 1-22 cycles), a hematologic response was seen in 49 patients (94.2%), including a complete response in 15 (28.8%), a very good partial response in 25 (48.1%), and a partial response in 9 (17.3%). At 6 weeks, 37 patients had already achieved a partial response. An organ response at 6 months was documented in 31 patients (59.6%). With respect to the cardiac response, a > 30% decrease in N-terminal pro-hormone brain natriuretic peptide (NT-proBNP) was observed in 17 of 35 evaluable patients (48.6%; NT-proBNP > 650 ng/L) at a median of 6 months. Overall survival was shorter for the patients with NT-proBNP > 5000 ng/L and for those who achieved less than a very good partial response. Conclusion Bortezomib is a safe and well-tolerated therapy for patients with AL amyloidosis with a rapid hematologic response and cardiac response, as assessed by the NT-proBNP level.

Background A major conclusion drawn from the accumulated cytogenetic data on solid tumors and some hematologic malignancies is that tumors progress by the acquisition of chromosomal changes, as reflected by more aggressive tumors containing a larger number of chromosomal abnormalities. An additional observation is that some chromosomal changes appear early in the disease progression, and some others appear late. Material and Methods On the basis of this information, a model for karyotypic evolution in chronic lymphocytic leukemia (CLL) is presented. The Mitelman Database of Chromosomes in Cancer was searched, and 1749 abnormal karyotypes were assessed. The main clones were analyzed, and chromosomal gains and losses were used to design a model of genetic acquisition based on the calculation of a variable called time to occurrence (TO). Results Our comprehensive study of genetic abnormalities in a large number of CLL karyotypes revealed that most CLL has 2 chromosomal aberrations at diagnosis. Moreover, the temporal analysis suggests that trisomy 12 is an early event in the biological evolution of CLL. Conclusion These results highlight the possibility of targeted therapies affecting the genes located on this chromosome (cyclin D, cyclin D2, cyclin-dependent kinase 2, and cyclin-dependent kinase 4).

Introduction Preclinical and clinical data suggest that bortezomib in combination with high-dose melphalan (Bor-HDM) provides with a synergistic effect able to improve response for MM patients undergoing auto-SCT. In the present study, patients receiving Cyclophosphamide, Bortezomib and Dexamethasone (CyBorD) induction followed by ASCT with Bor-HDM and HDM alone were evaluated. Methods All consecutive patients treated with CyBorD induction at our center from 01/2010 to 01/2015 were evaluated. All patients received induction chemotherapy before undergoing auto-SCT. Patients received conditioning with either HDM at 200 mg/m2 (or adjusted as per renal failure) or HDM with Bortezomib (Bor-HDM). Definitions of response and progression were used according to the EBMT modified criteria. MRD negativity was assessed by flow cytometry at day-100 post-ASCT. Results Clinical characteristics are shown in Table 1. Among 66 cases receiving CyBorD induction, 42 were conditioned with Bor-HDM and 24 with HDM. At the time of analysis, 90.5% and 91.7% of patients in the Bor-HDM and HDM group are still alive and 4 and 5 patients have already progressed, respectively. At day-100 post ASCT, ORR of 97%, with CR/VGPR rate of 81% was seen in the Bor-HDM group compared to 91% and 70% in the HDM group (p=0.2). MRD negativity was higher in the Bor-HDM group (29.2%) compared to HDM (9%) (p=0.04). Median OS and PFS was similar for Bor-HDM and HDM (p=0.8) with a median follow-up of 12 months. In conclusion, CyBorD is an efficacious regimen for patients with MM and overall seemed to be well tolerated. Our data is one of the first to show the impact of this regimen on MRD negativity rates after receiving HDM or Bor-HDM conditioning, suggesting that higher rates of MRD negativity are seen with Bor-HDM. Further evaluation on a prospective manner and longer follow-up is required to assess the impact of Bor-HDM on OS and PFS. Table 1 . Clinical Characteristics of patients with MM undergoing single auto-ASCT treated with CyBorD induction at our Institution Characteristic HDM (n=24) Bor-HDM (42) Age (median) 55 57 Gender Male Female 19 (79.1%) 5 (20.9%) 25 (59.5%) 17 (40.5%) Hb (g/L) 104 (75-157) 106 (76-139) Calcium (µmol/L) 2.3 (1.92-3.28) 2.3 (1.97-3.12) Creatinine (µmol/L) 86 (60-426) 84 (49-950) B2microglobulin (µmol/L) 2.73 (1.55-14.7) 3.41 (1.47-8.47) Albumin (g/L) 32 (21-43) 31 (16-42) Stage I Stage II Stage III 7 (29.1%) 14 (58.3%) 3 (12.5%) 6 (14.2%) 25 (59.5%) 11 (26.1%) LDH (IU/L) 172 (71-448) 192 (103-669) BMPC (%) 32% (5-84%) 38% (5-90%) Heavy chain: IgG IgA IgD Biclonal IgM FLC oncly 17(70.8%) 4 (16.6%) 0 1 (4.1%) 0 (1.5%) 2 (8.3%) 22 (52.3%) 10 (23.8%) 0 1 (2.3%) 1 (2.3%) 8 (19%) Light chain: Kappa Lambda Biclonal 17 (77.2%) 5 (20.8%) 1 (2%) 21 (50%) 20 (47.6%) 1 (2.3%) High risk (t(4;14), t(14;16), p53 del, del 13q by CC Standard risk 9 (37.5%) 15 (62.5%) 11 (26.1%) 31 (73.9%) BMPC: Bone marrow plasma cells; FLC: Free-light chains only; CC: Conventional cytogenetics Disclosures Jimenez-Zepeda: JJ Amgen: Honoraria; Celgene: Honoraria. Duggan: Jansen: Honoraria; Celgene: Honoraria. Neri: Celgene: Research Funding. Bahlis: Johnson & Johnson: Speakers Bureau; Johnson & Johnson: Consultancy; Amgen: Consultancy; Johnson & Johnson: Research Funding; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau.

Introduction : Cyclophosphamide, bortezomib and Dexamethasone (CyBorD) has become the standard frontline approach for the treatment of multiple myeloma (MM) in many centers across Canada. In the non-transplant eligible setting, recently a randomized controlled trial reported on the impact of Lenalidomide and Dexamethasone (LD), showing that this doublet-therapy is a feasible and efficacious combination. Based on the above-mentioned success of the LD combination, we aimed to compare the effect of CyBorD and LD for the treatment of non-transplant eligible MM (NTE) patients in the Alberta Myeloma and Dysproteinemia Program (AMDP). Patients and Methods : The primary objective was to assess ORR and PFS for NTE MM patients treated with CyBorD and LD. The recommended CyBorD regimen was as follows: bortezomib 1.3-1.5 mg/m2 SC or IV days 1, 8, 15 of a 28 day cycle (as of August, 2013 we adopted the a strategy whereby bortezomib can also be given on day 22), cyclophosphamide 300 mg/m2 PO days 1, 8, 15 and 22 and dexamethasone 20-40 mg PO days 1, 8, 15 and 22 with an aim to deliver a minimum of 9 cycles of treatment. LD was given at 25 mg days 1-21 of a 28-day cycle with Dexamethasone 20-40 mg PO days 1, 8, 15 and 22. Dose adjustments were at the discretion of the treating physician. Two-sided Fisher exact test was used to test for differences between categorical variables. A p value of

e260 of GF utilization occurred in the first 6 months and > 75% occurred in the first 9 months. BORT cost differentials were driven by higher usage intensity and cost per GF-using patient. Among 393 patients identified with second-line MM, monthly GF costs in the LEN-treated group declined from $211 at treatment initiation to $99 18 months later, while monthly GF costs in the BORT group increased from $364 to $693. Based on the Wilcoxon Rank-sum test, the difference between average GF costs per month across 18+ months after treatment initiation for MM patients was statistically significant ($242, p-value < 0.001) in favor of LEN. Treatment groups were comparable at baseline. Conclusion: BORT is associated with higher monthly GF use and cost during MM treatment, contributing to the significant overall cost disadvantage for BORT vs. LEN-based regimens.

e142 Conclusion: Sequential VAD and VTD, followed by high-dose melphalan with auto-SCT and bortezomib consolidation is an effective first-line treatment for patients younger than 65 years, with a comparable response rate and overall survival with various other regimens widely used in the current practice.

Introduction: AL amyloidosis is a clonal, non-proliferative plasma cell disorder characterized by the presence of light chain deposits among different tissues. Recently, bortezomib, has been reported to successfully induce hematological and cardiac responses for patients with AL amyloidosis. In addition, bortezomib has been combined with cyclophosphamide and dexamethasone (CyBorD), showing a high degree of hematological response. Based on the above mentioned, we aimed to assess the role of CyBorD in the treatment of patients with AL amyloidosis at our Institution. Methods: 40 consecutive patients have been treated with bortezomib-containing regimens at our center from 01/2010 to 01/2015. Among these cases, 22 (55%) have received CyBorD. Cyclophosphamide was given at 300 mg/m2 (PO) once weekly, dexamethasone 20-40 mg (PO) once weekly and Bortezomib 1.3 mg/m2 (IV or SQ) once weekly 3 out of 4 weeks in a 28-day cycle. The primary objective of the study was to assess rapidity of hematological and cardiac response. Results: Clinical characteristics are shown in Table 1. Median age at diagnosis was 63 years and 14 patients were male (63%). Three-cases have received prior therapies, ASCT in 1 and melphalan and dexamethasone in 2 patients. At the time of analysis, 19 patients are still alive and 3 patients have already progressed at a median follow-up of 11 months. A HR was seen in 19 out of 22 patients (ORR, 86%) after a median of 4 cycles (range, 1-19). CR (n1⁄46) and VGPR (n1⁄47) were seen in 13 cases (59%). Interestingly, partial response (n1⁄46, 27%) or better was seen after a median of 6 weeks in the responder cases. Organ response has been achieved in 59% of cases. Cardiac response based on high sensitive-troponin-T was seen in 6/10 cases (60%) and 7/11 (63%) based on NT-proBNP at a median of 12 and 6 months, respectively. CyBorD was well-tolerated and only one patient discontinued therapy due to autonomic neuropathy. No cases with cardiac involvement exhibited major decompensated CHF (congestive heart failure). In conclusion, CyBorD is an efficacious regimen for patients with AL Amyloidosis, providing with a high degree of organ and hematological responses. The impact of CyBorD on advanced heart dysfunction cases remains unclear but it seems that these patients still require a different approach maintaining a dismal prognosis.

e292 high-risk RRMM. A phase 2 study is underway to for further evaluation of HDLEN + MEL200 conditioning in ASCT. PO-366 Bendamustine-Bortezomib-Desametasone (BVD) in the Management of Relapsed and Refractory Multiple Myeloma : A Regional Real-Life Experience C. Cerchione, L. Catalano, A.E. Pareto, S. Basile, L. Marano, I. Peluso, L. Simeone, O. Vitagliano, S. Palmieri, S. Rocco, F. Ferrara, F. Pane Hematology, AOU Federico II e Napoli; Hematology, AORN A.Cardarelli, Napoli, Italy Bendamustine is a bifunctional alkylating agent, with low toxicity, proved to be effective in relapsed, refractory and in new diagnosed Multiple Myeloma (MM). It has been evaluated efficacy and tolerance of Bendamustine, in combination with bortezomib-dexametasone (BVD) in patients with relapsed and refractory MM (rrMM), whose prognosis is particularly severe. A regional retrospective real-life analysis of patients with rrMM who had been treated with BVD as salvage therapy has been performed. 35 patients (19 M/16 F), with rrMM, median age at diagnosis 57 years (r. 36-82), median age at start of treatment 62 years (r.37-83) treated with several lines of treatments (median 6, r. 2-11), every refractory to all the drugs previously received (also Bortezomib), received BVD (Bendamustine 90 mg/sqm days 1,2; Bortezomib 1.3 mg/sqm days 1,4,8,11, Desametasone 20 mg days 1,2,4,5,8,9,11,12, Pegfilgrastim day +4) every 28 days, until progression. ISS was equally distributed, and cytogenetic was evaluable in 9 patients, and in particular one del13q and one t(11;14). All the patients had previously been treated with schedule containing bortezomib and IMIDs, 90% of them with melphalan, 77% with cyclophosphamide, 34% with antracyclines and 30% had also received radiotherapy. 58% of them had undergone at least to a single auSCT. All patients were relapsed and refractory to last therapies received before BVD. Bendamustine was well tolerated, with grade 3 transfusiondependent anemia in 29% of patients, and 41% grade 3 neutropenia (no ospedalization was required, no septic shocks were observed). No severe extrahematologic toxicity was observed, only grade 1 gastrointestinal side effect (nausea), treated by common antiemetic drugs. According to IMWG, after a median follow-up of 9 months (r.2-36), ORR was 54% (1 CR, 1 VGPR, 9 PR, 8 MR) with 7 PD and 9 patients in SD, which can be considered as an impressive result in this subset of rrMM patients. In particular, for 4 patients, BVD was, after having achieved a PR, a bridge to second auSCT, and for one patient a bridge to auSCT. Median OS from diagnosis was 61.4 months (range 6-151), median OS from start of Bendamustine was 7.2 months (range 2-36). BVD has shown significant efficacy (ORR 54%) in a particular severe setting of patients, relapsed and refractory to all avaiable therapeutic resources, and in particular cases it could be considered as a bridge to a second autologous or allogenic BMT. 15th International Myeloma Workshop, September 23-26, 2015 PO-367 Pomalidomide-containing regimens for the treatment of relapsed and refractory Multiple Myeloma V.H. Jimenez-Zepeda, P. Duggan, P. Neri, C. Ahsan, F. Rashid-Kolvear, N. Bahlis Tom Baker Cancer Center, Department of Medical Oncology and Hematology; Calgary Lab Services, Calgary, AB, Canada Introduction Pomalidomide is an IMiD that was recently approved for the use of relapsed MM failing lenalidomide and bortezomib. In the present study, we aimed to evaluate the efficacy of pomalidomide and dexamethasone (PD) for heavily-pretreated relapsed or refractory MM (RRMM) at our Institution. Methods We retrospectively reviewed the records of all patients with RRMM treated with Pomalidomide-containing regimens (PCR) at Tom Baker Cancer Center between 01/10 and 04/15. Patients received oral pomalidomide 2-4 mg/d on days 1-21/28, and dexamethasone 20 mg or 40 mg on a weekly basis, few cases were treated with PD in addition to bortezomib or cyclophosphamide. Definitions of response and progression were used according to the EBMT modified criteria. A p-value was considered statistically significant if