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Abstract Background: The presence of circulating myeloma cells (CMC) detected by flow cytometry at the time of diagnosis of multiple myeloma is associated with a shortened response to therapy and reduced overall survival (OS). We hypothesized that the presence of CMC at the time of stem cell collection prior to high dose therapy (HDT) and autologous stem cell transplantation (ASCT) would identifies a cohort of patients with a high risk of rapid progression. Methods: The Mayo Clinic myeloma transplant database was queried for patients who were mobilized using cyclophosphamide and hematopoietic growth factors. CMC was determined using flow cytometry by gating on a population of CD38 bright and CD45 negative cells. The impact of CMC on OS and time to progression (TTP) and its role in the context of established prognostic parameters was evaluated. Results: Of 246 patients with MM undergoing ASCT, 95 had CMC. Patients with CMC had significantly higher plasma cell labeling index, adverse cytogenetics, B2-M and resistant disease. Complete response (CR) rates post transplant were 32% and 36% for patients with and without CMC (p=0.5034). OS was 33.2 and 58.6 months (p=0.0052) while TTP was 14.1 and 22 months respectively (p=0.0005). Figure Figure On multivariate analysis, CMC remained an independent prognostic factor in a model that included cytogenetics and disease status at time of transplant (p=0.0314). A prognostic system based on the presence or absence of CMC and karyotype abnormalities was developed. Patients with neither, one or both parameters had a median, OS of 55, 48 and 21.5 months respectively (p<0.0001) while TTP was 22, 15.4 and 6.5 months for the same groups (p<0.0001). Conclusion: The presence of CMC at the time of HDT and ASCT is an independent prognostic factor. The combination of CMC and cytogenetics provides a simple yet powerful scoring system that stratifies patients and guides their management.

Abstract Background: Solitary plasmacytoma of bone (SBP) is a localized collection of monoclonal plasma cells that is potentially curable with local radiation therapy but associated with a high risk of progression to multiple myeloma. We hypothesized that an abnormal immunoglobulin free light (FLC) ratio at diagnosis may be a prognostic indicator of transformation risk. Methods: We identified a cohort of 133 patients with SBP for whom stored serum taken at the time of diagnosis was available. The diagnosis was ascertained and serum FLC determined in 126 patients. Results: From this cohort, 48 patients have progressed to myeloma and the median time to progression among those who progressed was 1.9 years. On univariate analysis, age (p<0.001), gender (p=0.035), abnormal FLC ratio at diagnosis (p=0.009) and persistence of serum or urine M-protein after therapy (p=0.0070 were all associated with a shorter overall survival (OS) and time to progression to multiple myeloma. Progression by Normal FLC(0.26–1.65) Progression by Normal FLC(0.26–1.65) On multivariate analysis, an abnormal FLC ratio retained its independence in a model that includes age at diagnosis but lost its significance when combined with persistence of the serum or urine M-protein. However, serum or urine M-proteins are not detectable in a significant number of patients with SBP and therefore not informative. Conclusion: The FLC ratio at the time of diagnosis of SBP is a powerful predictor of risk and a useful aid to management of patients with this condition.

Abstract Introduction: The kidney is affected by immunoglobulin light chain amyloidosis (AL) in more than 50% of patients who present with the disease, but long-term predictors for and outcomes after renal replacement therapy have not been well described in this patient group Patients: 145 patients with AL who participated in Mayo Clinic treatment trials and were monitored for at least 11 years. No patient was lost to follow-up Results: Among patients presenting with renal AL, 42% ultimately received renal replacement therapy compared with 5% of patients who did not have an initial presentation involving the kidney. Table 1. Monoclonal Protein Studies in 145 Patients With Immunoglobulin Light Chain Amyloidosisa Patients, No. (%) Monoclonal Protein Renal Amyloid at Presentation (n=84) Nonrenal Amyloid at Presentation (n=61) a P=.02 l more likely to cause renal presentation None 7 (8) 2 (3) k 6 (7) 12 (20) l 71 (85) 47 (77) Table 2. Characteristics of All 145 Patients With Immunoglobulin Light Chain Amyloidosis Amyloid Renal (n=84) Nonrenal (n=61) P Value Abbreviations: IQR, interquartile range; NA, not applicable. a included in the definition of renal amyloidosis Patients with l immunoglobulin light chain amyloid were significantly more likely to have renal involvement and had significantly greater urinary protein loss than patients with κ or no monoclonal light chain amyloid Age, median (IQR), y 61 (52–67) 62 (55–68) .47 Sex, male/female 52/32 40/21 .72 24-hr urine protein loss, median (IQR), g/d 7.0 (4.4–11.7) 0.3 (0.1–6.4) NAa Creatinine, median (IQR), mg/dL 1.1 (0.9–2.2) 1.1 (0.9–1.3) .22 Cardiac involvement (yes/no) 35/48 48/16 .0001 Table 3 Distribution of Urinary Protein and Creatinine Based on Monoclonal Protein Monoclonal Protein Test k (n=18) l (n=118) None (n=9) P Value Abbreviation: IQR, interquartile range. Patients with renal amyloid who ultimately received dialysis support had significantly higher serum creatinine and 24-hour urine protein levels at presentation. Absence of cardiac involvement at diagnosis predicted an increased likelihood of dialysis All patients (N=145) 24-hr urine protein loss, median (IQR), g/d 0.73 (0.16–2.37) 3.61 (0.35–7.8) 5.68 (0.3–12.2) .001 Creatinine, median (IQR), mg/dL 1.1 (0.9–1.3) 1.1 (0.9–1.3) 1.5 (1.2–1.6) NS Patients with renal amyloid at presentation (n=84) 24-hr urine protein loss, median (IQR), g/d 2.93 (1.1–5.0) 7.2 (4.8–11.8) 7.8 (3.8–12.6) .04 Creatinine, median (IQR), mg/dL 1.0 (0.8–2.6) 1.1 (0.9–2.2) 1.5 (1.1–1.6) NS Table 4 Characteristics of 84 Patients Presenting With Renal Amyloidosis Dialysis Subsequently Not Required Characteristic Required (n=35) (n=49) P Value Abbreviation: IQR, interquartile range. The median time from diagnosis to dialysis was 29.5 months for those that went into renal failure.). However, the actuarial risk reached 50% at 12 years Kaplan-Meier failure curve demonstrating the actuarial time from diagnosis to the start of dialysis therapy N=145 For 38 patients who received dialysis, median survival from day 1 of dialysis was 10.4 months Kaplan-Meier survival of 38 patients from the start of dialysis therapy Age, median (IQR), y 60 (52–67) 62 (52–67) .90 Sex, male/female 21/14 31/18 .76 24-hr urine protein loss, median (IQR), g/d 7.4 (5.0–14.8) 5.9 (3.7–9.1) .03 Creatinine, median (IQR), mg/dL 1.4 (0.9–2.8) 1.1 (0.9–1.5) .01 Cardiac involvement (yes/no) 9/26 26/23 .01 Conclusion: In our study, 26% of all patients with AL ultimately received renal replacement therapy compared with 42% of patients who presented with renal AL specifically. The presenting 24-hour urine protein loss and creatinine values predict which patients will require dialysis. Median survival for patients starting dialysis is less than 1 year. Presence of l light chain amyloid predicts an increased likelihood of renal involvement and, when the kidney is affected, increased proteinuria.

Abstract Introduction: The Bone Marrow Transplant Program at Mayo Clinic (Rochester, Minnesota) developed a multidisciplinary approach (involving physicians, nurses, pharmacists, dietitians, and financial specialists) for outpatient management of patients undergoing stem cell transplantation. This approach uses an electronic ordering system for diagnostic tests and chemotherapy to minimize medical errors. Table. Patient Characteristics (N=716) Characteristic Value Male, no. of patients (%) 426 (59) Age, median (IQR), y 59 (53–65) Creatinine, median (IQR), mg/dL 1.0 (0.9–1.2) b2-Microglobulin, median (IQR), mcg/mL 2.5 (1.9–3.7) Gammopathies, no. of patients (%) Measured by serum immunofixation or immunoelectrophoresis IgA 148 (21) IgG 414 (58) IgM 6 (1) IgD 12 (2) Light chain 83 (12) Biclonal 6 (1) None 47 (7) Measured by urine immunofixation or immunoelectrophoresis k light chain 402 (56) l light chain 226 (32) Biclonal 1 (0) None 79 (11) Not performed (anuric) 8 (1) Status at stem cell transplant, no. of patients (%) Untreated 4 (1) Plateau 436 (61) Primary refractory 113 (16) Relapse after therapy 93 (13) Relapse during therapy 70 (10) Characteristic Value CD34+ cells, median (IQR), ×106/kg Collected, no. 10.0 (7.6–12.6) Infused, no. 4.7 (3.9–6.2) Sessions of apheresis, median (IQR) 3 (2–5) Engraftment, median (IQR), days after transplantation Neutrophils, 0.5×109/L 13 (12–15) Platelets, 50×109/L 16 (14–22) Duration of hospitalization, median (IQR), d 4 (0–10) Abbreviation: IQR, interquartile range. Results: During a 45-month period after implementation of the program (2005-Sept 2007), the day-100 survival rate was 99.5% for low-risk myeloma patients (transplantation during first plateau; n=202) and 97% for high-risk myeloma patients (refractory, relapsing or second or greater plateau; n=71). The overall day-100 survival rate was 99%(270/273). Analysis of hospitalization trends since inception of the program showed that 39% of patients completed the transplant procedure as outpatients. The median duration of hospitalization for all patients was 4 days; age and serum creatinine levels were predictive of the need for and duration of hospitalization Conclusion: Outpatient stem cell transplantation is feasible for patients with multiple myeloma with a therapy mortality of 1%. Nearly 40% of our patients completed the procedure without hospitalization. Age and serum creatinine levels predicted a higher likelihood of hospitalization. Implementation of out patient transplant requires affordable housing in the community since many third party payers do not support hotel costs despite the reduction of hospital days. The hospital physical plant and patient registration process has to support use of designated hospital rooms for purely out patient practice. The transplant team must have process owners to standardize across all disease categories collection protocols, conditioning regimens, infusion SOP’s and post infusion supportive care guidelines for standard antibiotics, narcotics, laboratory work and transfusion thresholds. A care team meeting between physicians, nursing, dietary, pharmacy, business office, data base and appointment coordinators is essential to coordinate all the multidisciplinary efforts. Kaplan-Meier curve shows the percentage of patients remaining in the hospital through time t, stratified on the basis of age greater than or less than or equal to 65 years Kaplan-Meier curve shows the percentage of patients remaining in the hospital through time t, stratified on the basis of age greater than or less than or equal to 65 years Kaplan-Meier curve shows the percentage of patients remaining in the hospital through time t, stratified on the basis of creatinine greater than or equal to or less than 1.5mg/dL Kaplan-Meier curve shows the percentage of patients remaining in the hospital through time t, stratified on the basis of creatinine greater than or equal to or less than 1.5mg/dL

Abstract Introduction: Immunotherapy is most likely to work in a setting of low tumor burden, making vaccine strategies attractive as maintenance therapy post autologous peripheral blood stem cell transplantation (PBSCT) for multiple myeloma (MM). However, it is difficult to ascertain the effects of the vaccines from delayed responses to the transplant. A novel immunotherapeutic, APC8020 (Mylovenge), was studied as consolidation therapy after for MM post PBSCT (Mayo vaccine trial). Mylovenge is prepared from autologous antigen presenting cells, including dendritic cells, partially purified from an unmobilized leukapheresis product by gradient density isolation and then incubated for two days with autologous serum containing M protein obtained pretransplant. We report long term results of the Mayo vaccine trial compared retrospectively to a consecutive cohort of MM patients who underwent autologous stem cell transplant at Mayo Clinic during the same time period. Methods: The Mayo vaccine trial patients had transplants between July of 1998 and May of 2001. Using these cutoff dates we analyzed 151 total MM patients, 27 from the vaccine trial (9 newly diagnosed and 18 relapsed) and 124 from database (DB) (50 newly diagnosed patients and 74 relapsed). The median (range) of follow-up for alive patients in vaccine trial is 6.5 years (2.9 – 8), and in the DB is 7.1 years (6 – 8). Two-sided Fisher’s exact tests and stratified log rank tests (with newly diagnosed or relapsed as the stratum) were used to compare baseline patient characteristics and time to event distributions (overall survival – OS, progression free survival – PFS, and time to progression – TTP) between the two groups. Results: The median (range) of age in vaccine trial and DB was 56 (30–69) and 57 (36–71) years respectively. There were no significant differences in the known prognostic factors including PCLI, B2M, and CRP. The median (95% confidence interval - CI) TTP for the vaccine trial and DB patients was 1.5 years (1.3 – 2.4) and 1.6 years (1.3 – 1.8); stratified log rank p value = 0.46. The median (95% CI) PFS for the vaccine trial and DB patients was 1.5 years (1.3 – 2.4) and 1.5 years (1.1 – 1.8), stratified logrank p value = 0.30. The median (95% CI) OS for the vaccine trial and DB patients was 5.3 years (4.0 -N/A), and 3.4 years (2.7 – 4.6); stratified logrank p value = 0.02. Conclusions: Despite the fact that no difference was seen in TTP or PFS, post-transplant vaccine therapy was associated with prolonged survival. This is similar to what has been reported in other tumor systems including prostate cancer and glioblastoma multiforme. This approach warrants further investigation, including preclinical studies aimed at optimizing the immune response and randomized trials to define the role of vaccine therapy in myeloma. Figure Figure

Abstract Introduction: We retrospectively analyzed outcomes of 716 patients with multiple myeloma who were mobilized using cyclophosphamide and growth factor (n=370) or growth factor alone (n=346) before stem cell transplantation. Table. Patient Characteristics (N=716) Variable Cyclophosphamide (n=370) Growth Factor Only (n=346) P Value Abbreviation: IQR, interquartile range. *Or equivalent dosage. Men, No. of patients (%) 224 (61) 202 (58) .50 Age, median (IQR), y 58 (52–64) 60 (53–65) .11 b-2 Microglobulin, median (IQR), mcg/mL 2.7 (1.9–4.0) 2.3 (1.9–3.2) .01 Creatinine, median (IQR), mg/dL 1.1 (0.9–1.3) 1.0 (0.8–1.2) .002 Apheresis, median (IQR) collections, No. 2 (1–3) 4 (3–6) .001 Marrow plasma cells, % 17 (5–34) 5 (1–13) .001 CD34+cells, median (IQR), cells/kg Total collected 10.3x106(7.2x106–14.6x106) 9.9x106(7.6x106–11.9x106) .01 Infused 5.6x106(4.5x106–7.6x106) 4.2x106(3.8x106–5.0x106) <.001 Duration of hospitalization, median (IQR), d 4 (0–10) 4 (0–9) .92 Nonstaphylococcal bacteremia, No. of patients (%) 48 (13) 25 (7) .01 Melphalan dosage, No. of patients (%) .04 200 mg/m2* 337 (91) 298 (86) 140 mg/m2* 33 (9) 48 (14) Exposure before mobilization, No. of patients (%) Melphalan 45 (12) 44 (13) .50 Lenalidomide 14(4) 63(18) .01 Results: Patients receiving cyclophosphamide had higher stem cell yields than the growth factor only group (median number of apheresis sessions needed to achieve stem cell collection goals, 2 vs 4 sessions, respectively [P=.001]). However, patients treated with cyclophosphamide required more time for engraftment of platelets and neutrophils (P<.001 for both). For patients receiving cyclophosphamide, 75% achieved engraftment (defined as a platelet count of 50x109/L) by day 39, whereas 75% of patients not receiving cyclophosphamide achieved engraftment by day 18. Similar results were observed for neutrophil engraftment. These differences did not affect the duration of hospitalization, but patients treated with cyclophosphamide had a higher incidence of posttransplant nonstaphylococcal bacteremia. For cyclophosphamide-mobilized patients, considerably faster platelet engraftment (5 fewer days) resulted if stem cell reinfusion occurred more than 30 days after the first apheresis session. Conclusion: Our data suggested that cyclophosphamide damaged the microenvironment and slowed engraftment. By lengthening the period between the completion of apheresis and stem cell reinfusion, the microenvironment may recover and result in faster engraftment. We suggest that the cyclophosphamide used for mobilization may affect the marrow microenvironment. Cyclophosphamide improves yields but increases bacteremia rates after transplantation. Cyclophosphamide increases time required to collect stem cells and slows engraftment. Figure Figure

Abstract Background: Primary systemic amyloidosis (AL) is an incurable plasma cell disorder with a poor survival, especially in patients (pts) with multiple organ involvement. For pts with limited organ involvement, high dose chemotherapy with autologous stem cell (SCT) support is an effective approach. However, the toxicity of SCT limits its widespread use. Melphalan and dexamethasone has been previously shown to be effective in pts ineligible for SCT. Methods: We reviewed our experience with melphalan and dexamethasone for treatment of AL. Eighty one pts were treated between 2001 and 2003; median age at start of therapy was 63 years (range, 38–80) and 56 pts (69%) were males. Among these, 46 pts (57%) had 2 or more major organs (cardiac, renal, hepatic) involved. Intravenous melphalan (IV) was used in 45 pts (56%), 32 (40%) received oral melphalan (PO) and the rest received cycles of both. The most common doses were 16 mg/m2 for IV administration (every 4–6 weeks) and 0.22 mg/kg for PO administration (every 4 weeks). Dexamethasone was usually given at a dose of 40 mg for the first 4 days of each cycle. Results: Patients received a median of 5 cycles (range; 1–17). At the time of analysis, 53 (65%) pts were alive with a median follow up of 10.8 months (range, 1.4–47.1).The estimated median overall survival (OS) was 25.6 months for the entire group, with the number or type of organs involved not impacting survival. Hematological response (HR) was defined by a 50% reduction in either serum M-spike, urine M-spike, or the absolute difference between the involved and uninvolved immunoglobulin free light chains. A HR was observed in 43 pts (67%) of the 64 pts measurable for HR by conventional criteria. Achievement of HR was associated with a superior OS with a median post-therapy OS that was not reached, while non-responders had a median OS of 11.1 months (p<0.0001) (Figure 1). Among these pts, an organ response as defined by conventional criteria, was seen in 14 pts (22%), which was significantly correlated with obtaining a hematological response (33% vs. 5%, p=0.01). A 25% reduction in the difference between the involved and uninvolved FLC strongly predicted prolonged OS, with a median post-therapy OS that was not reached for responders vs. 11.3 months for non-responders (p<0.0001) (Figure 2). A decrease in post-therapy brain natriuretic peptide (BNP) also predicted for a survival improvement, with the median OS not reached for responders vs. a median OS of 17 months for non-responders (p<0.016). Conclusion: Treatment with melphalan and dexamethasone is effective and a significant survival advantage is achieved in patients with a hematological response. FLC and BNP response can help identify patients that are likely to benefit from this therapy. Figure Figure Figure Figure

Abstract Background: Primary systemic amyloidosis is an uncommon plasma cell dyscrasia characterized by organ deposition of immunoglobulin light or heavy chain fragments. It is related to the other plasma cell dyscrasias such as multiple myeloma and monoclonal gammopathy of undetermined significance. cIg-FISH on bone marrow plasma cells has become well established in the initial evaluation of myeloma as the t(4;14), t(14;16),13q-, and the 17p- abnormality are of major prognostic value. The corresponding data does not exist in amyloidosis, as there are only three small studies published to date. Methods: Using a prospectively held dysproteinemia database, we reviewed all cases of amyloidosis seen at our institution who had cIg-FISH or cytogenetics performed as part of their routine clinical testing. Three hundred thirty nine patients were identified with amyloidosis and cytogenetic testing. Of these 69 had cIg-FISH testing results. cIg-FISH was performed with fluorescent-tagged antibodies to kappa/lambda immunoglobulin and FISH probes corresponding to the following anomalies: trisomies 3, 7, 9 and 15; del17p/-17; -13/del13q; 14q32 split; and t(11;14). CCND1/IGH. If an IGH rearrangement was detected that did not involve CCNDI, we also evaluated t(4;14) or IGH/FGFR3 and t(14;16) or IGH/c-MAF. These probes constitute the standard screening panel used in MM at our institution. Results: The study population had a median age of 61 years with a male to female ratio of 1.6:1. Median follow up time was 13.5 months. By conventional cytogenetics, 88% of patients had no detectable abnormality. In contrast, only 33% were normal by cIg-FISH. The abnormalities demonstrated were 28% 13-/del13q, 42% IgH translocation, 33% t(11;14), and 3% t(14;16). No patients had a -17/del 17p- or t(4;14). Nine patients had del13q/-13 with an IgH translocation, with 7 of these having t(11;14). Both t(14;16) patients had del 13q. A trend towards increased mortality was seen in patient with any abnormality (p=0.11), but this could not be demonstrated for any single abnormality, likely due to lack of statistical power. There was no correlation between renal involvement or cardiac involvement and cIg-FISH results. Conclusion: The majority of chromosomal abnormalities in amyloidosis are undetected by conventional cytogenetics. With further study, chromosomal abnormalities may carry the same prognostic value in amyloidosis that they currently enjoy in myeloma. This effect may be independent of currently recognized risk factors. Chromosomal abnormalities in Amyloidosis as detected by cIg-FISH Abnormality Amyloidosis % (n=69) Normal 33(23) −13/del13q 28(19) IgH Abnormality 42(29) t(4;14) 0(0) t(11;14) 33(23) t(14;16) 3(2) del 17 0(0) Other 3(2)

Abstract BACKGROUND: We sought to determine the prognostic relevance of aberrant serum lipid values in the myeloproliferative disorders (MPDs) of primary myelofibrosis (PMF), polycythemia vera (PV), and essential thrombocythemia (ET). METHODS: The Mayo MPD patient institutional database was queried to identify clinical history and lipid profiles (within a year of diagnosis). Serum cholesterol (CHOL), low density lipoprotein (LDL-C), high density lipoprotein (HDL-C), and triglycerides (TRI) were assessed compared to clinical outcomes. RESULTS: 558 patients with MPDs (PMF 28%, PV 27%, and ET 45%) (median age at diagnosis of 56 (range18–81)) were identified. A lipid profile obtained a median of 0.0 months from diagnosis (range (-8 to 12 months) from MPD patients displayed low CHOL, LDL-C, and higher HDL-C than typical for the USA. Amongst MPD disease types PMF patients had lower CHOL (p<0.001) and HDL (p<0.001) compared to ET and PV (see table). Amongst PMF patients, although hypocholesterolemia was not a surrogate for malnutrition (p=0.13) median serum albumin 4.1 g/dL (range 2.7–4.8)), there was correlation with the presence of weight loss, hypercatabolic symptoms, and worse Mayo-CBC myelofibrosis prognostic scores (Cancer2006;106:623; p<0.01). Amongst the study group PMF patients had the poorest survival (followed by PV then ET; p<0.001). Decreased cholesterol (CHOL <150mg/dL, or HDL <60 mg/dL) was associated with decreased survival (P<0.001), but only in PMF patients (see figure). Decreased PMF survival was also associated with traditional PMF risk factors of hemoglobin <10g/dL, leukocytes <4 or >30 × 10(9)/L, platelets <100 × 10(9)/L, and circulating blasts. In multivariate analysis (Cox-Proportional Hazard) only the Mayo-CBC score, hemoglobin <10g/dL, circulating blasts and decreased CHOL remained significant for decreased survival (p<0.001). CONCLUSIONS: The presence of hypocholesterolemia is very common in patients with PMF and is independently associated with inferior survival. Survival by HDL-C and Serum Cholesterol (CHOL) in 154 patient’s with Primary Myelofibrosis Survival by HDL-C and Serum Cholesterol (CHOL) in 154 patient’s with Primary Myelofibrosis Lipid Distributions in 558 MPD patients VALUE/ NCEP CATEGORY PMF (N=154) PV (N=149) ET (N=255) NHANES (USA MEANS;95th CI) NCEP: National Cholesterol Education Program: NHANES (National Health and Nutrition Examination Survey (values for all races ages 65–74) Serum Cholesterol (Median) 149 mg/dL 179 mg/dL 199 mg/dL 221 mg/dL (153–301) −>200mg/dl (Desirable) 10% 31% 48% −150–200mg/dL (Desirable) 39% 25% 41% −100–149mg/dL (Desirable) 41% 41% 9% −<100mg/dL (Low) 10% 3% 2% LDL Cholesterol (Median) 33 mg/dL 41 mg/dL 49 mg/dL 149 mg/dL (87–217) −>100mg/dL (Low to high risk) 1% 1% 1% −<100mg/dL (Optimal) 99% 99% 99% HDL Cholesterol (Median) 79 mg/dL 118 mg/dL 108 mg/dL 45.7 mg/dL (29–71) −>60mg/dL (Optimal) 74% 90% 91% −40–60mg/dL (Normal) 16% 10% 8% −<40mg/dL (Low) 10% 0% 1% Triglycerides (Median) 151 mg/dL 89 mg/dL 116 mg/dL 145 mg/dL (62–285) −>200mg/dL (High) 28% 0% 3% −150–199mg/dL (Borderline) 23% 6% 14% −<150mg/dL (low) 49% 94%% 83%

Abstract Background: Recent advances in the therapy of multiple myeloma (MM) have greatly increased the treatment options for this uniformly fatal plasma cell malignancy. It is not clear if introduction of novel therapies and the increased use of high dose therapy (HDT) in the past decade have translated into better outcome for patients (pts) with MM. Methods: We examined the outcome of two cohorts of pts seen at our institution. The first cohort consisted of 387 pts who relapsed after HDT and was examined for potential improvement in survival following relapse after HDT. These pts were divided into two groups; those who relapsed before or after December 31, 2000. The second cohort consisted of 2981 patients with newly diagnosed MM seen between January 1971 and December 2006 and was used to examine the trends in overall survival (OS). Results: Among those relapsing after HDT, there were 245 males (63%); median (range) age at HDT was 57 years (32.8–75.4) and the median time to HDT was 8.1 months (1–90 months) from diagnosis. The median time to relapse was 13.2 months (1.1 months-10.3 years) from HDT. In this cohort, a clear improvement in OS from time of relapse was seen over the past decade, with those relapsing after 2000 having a median OS of 23.9 months (95% CI; 19.8, 27.6) compared to 11.8 months (95% CI; 8.7, 14.9) for the rest (P < 0.001) (Figure 1). In a multivariate analysis, the effect of the date of relapse on survival was independent of other prognostic factors such as relapse <12 months after HDT, abnormal cytogenetics, and B2M > 5.5 mg/dL. Pts who were treated with one or more of the newer drugs (thalidomide, lenalidomide, bortezomib) had longer survival from relapse (30.9 months (95% CI; 23.6, 38.2) compared to 14.8 months (95% CI; 11.3, 18.4); P < 0.001) for others. Among the newly diagnosed MM cohort, the median age at diagnosis was 66 years (20.2 – 97 years), and 1,770 (59.4%) were males. The median follow up for the entire group was 27.4 months (0–29.4 years); and at the time of analysis 558 patients (18.7%) were alive with a median follow up of 32.7 months (0–29.4 years). Pts diagnosed in the last decade had an improved OS (44.8 months) compared to those diagnosed before this period (29.9 months; P < 0.001) (Figure 2). The improvement in survival seen in the last decade among newly diagnosed patients was predominantly among those younger than 65 years (60.3 mos vs. 33.3 mos improvement in median survival); compared to those over 65 at diagnosis (26.5 mos vs. 32 mos). Conclusion: In this study, for the first time, we demonstrate definite proof for improved outcome in patients with myeloma, both in the relapsed setting as well as at diagnosis, a change that is likely to continue with increased use of these drugs. Figure Figure Figure Figure