ALBERT

Description: Background The median age at diagnosis of MM is 69 years. Randomized, controlled studies on the safety and effectiveness of AHCT are lacking in those 〉 70 years of age and many patients are considered “ineligible” on the basis of age. We analyzed survival (OS) outcomes of 11,430 MM patients from US and Canada receiving AHCT after high dose melphalan (MEL) between 2008 -2011 reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). The relative efficacy of AHCT was compared in 3 cohorts; those aged ≥70 years (Cohort 1, n=946) vs. those 60-69 years (Cohort 2, n= 4666) and vs. 18-59 years (Cohort 3, n=5818). A statistically representative subset of 1279 patients was then analyzed in further detail to compare relapse, progression free survival (PFS) and non-relapse mortality (NRM). Results The median ages in group 1, 2, and 3 were 72, 64 and 53 years, respectively with an upper age of 89 years. The older age cohort 1 was composed of a higher proportion of male patients, IgA MM, US patients (vs. Canada) and had worse Karnofsky scores (KPS 〈 100) and co morbidity scores (HCTCI ≥ 2), (all p values 12mo) interval from diagnosis to AHCT and inferior disease status (

Description: The reported incidence of t-MDS/t-AML following traditional ASCT for lymphoma ranges between 0–12%. Previously identified risk factors include older age, prior alkylator therapy and use of radiation either prior to ASCT or as part of the preparative regimen. It is unclear whether novel conditioning regimens for ASCT that utilize targeted RIT with the potential to deliver higher radiation doses to the marrow are associated with a higher risk of t-MDS/t-AML. We identified a case-series of 83 pts who underwent RIT based ASCT between 06/00 and 01/06 to evaluate the incidence of t-MDS/t-AML; Forty-one pts received standard dose 90Y ibritumomab tiuxetan (0.4mci/kg: median dose 32.9 mci (range 20–40)) in combination with high dose BEAM (BCNU 450mg/m2, etoposide 800mg/m2, cytarabine 800mg/m2, melphalan 140mg/m2) and 42 pts received high dose 90Y based on dosimetry (median 70.8 mci range 36–105) in combination with etoposide 60mg/kg plus cyclophosphamide 100mg/kg. Pts were followed prospectively post ASCT with serial bone marrow biopsies approximately annually. The median age at ASCT was 54 years (range 19–78). Disease histology included diffuse large cell n=40, follicular NHL n=17, mantle cell n=21, transformed n=4, SLL n=1. Disease status at ASCT was 1st CR n=17, 1stPR n=14, induction failure n=14, 1st relapse or greater n=38. With a median follow-up of 39 months (range, 1.4–83), three patients (3.61%) have developed t-MDS/t-AML. The three pts also had associated complex chromosomal abnormalities including de1(13q), del(5q), del (20q). The median time to t-MDS/t-AML was 2.63 years (range, 1.51 – 8.41) post NHL diagnosis and 1.99 years (range, 0.56 – 5.10) post ASCT. The cumulative incidences of t-MDS/t-AML at 1 and 2 years were 1.20% (95%CI, 0.17– 8.1%) and 2.60% (95%CI 0.64–9.9%). None of the potential risk factors including age(〉50 at ASCT) (p=0.33), prior radiotherapy (p=0.99), number of prior regimens (p=0.5) and 90Y dose (p=0.99) were statistically significant by univariate analysis. As 82/83 pts had received prior alkylator therapy this was not analyzed as a separate risk factor. Two year overall survival for the entire cohort is 90% (95%CI 83–95). Although the follow up is relatively short, the incidence of t-MDS/t-AML is consistent with our previous institutional experience in ASCT patients who received non-RIT based conditioning (Krishnan et al. Blood 2000) and with the 2.5% incidence of t-MDS/t-AML observed in pts receiving 90Y in registration and compassionate use trials (Czuczman et al JCO 2007 in press). In conclusion RIT based conditioning does not appear to confer an increased risk of t-MDS/t-AML above what has been previously reported with traditional ASCT preparative regimens. Incidence of t-MDS/t-AML Incidence of t-MDS/t-AML

Description: Background: TAK-079 is a subcutaneously (SC) administered, mAb which exhibits more selective binding to human CD38 protein expressed by myeloma cells and less cross reactivity with the CD38 antigen present on red blood cells and platelets. It depletes myeloma cells via apoptosis antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and antibody-dependent cellular phagocytosis (ADCP). TAK-079 was safe and well-tolerated in a first in human study in healthy subjects with potent pharmacodynamic activity when administered as a SC injection (Fedyk et al ASH 2018; abstract 3249). Methods: A multicenter phase 1 study (NCT03439280) evaluating safety, pharmacokinetic (PK), pharmacodynamics, and efficacy of TAK-079 in patients with heavily pretreated RRMM was initiated. Pt with RRMM were eligible after at least 3 lines of therapy and previous exposure to immunomodulatory drug (IMiD), proteasome inhibitor (PI), alkylating agent, and corticosteroid with or without an anti-CD38 or SLAMF7 antibody. Patients were refractory or intolerant to at least 1 PI and 1 IMiD. Ph 1 dose escalation proceeded using a 3+3 design. The TAK-079 dose was given as a SC injection weekly for 8 doses, every other week for 8 doses, then monthly until disease progression (PD) or unacceptable toxicity. Results: 31 patients have been enrolled across 4 dose cohorts (TAK-079 45-135-300-600 mg fixed dose SC); data is available on 28 patients as of the 14 June 2019 data cutoff. Median age was 65 (53-81) years. ISS stage at study entry was I/II/III/missing in 42%, 32%, 19%, 6% of patients respectively, 94% of patients were refractory to either a PI or IMiD and 61% were refractory to both, 23% of patients were previously exposed to at least 1 anti-CD38 monoclonal antibody; 84% had a prior stem cell transplant. The maximum volume of a SC injection was 2 mL, resulting in an administration duration of ≤ 1 minute. No ≥ Grade 1 early or late systemic infusion reactions have been reported. One (

Description: Background:The Blood and Marrow Transplant Clinical Trials Network 0803 study confirmed the safety and efficacy of ASCT in HIV-infected patients with lymphoma. Short term toxicity and transplant related mortality was low (5.2%) and engraftment, treatment-related mortality and survival outcomes were not statistically significantly different from that of age and diagnosis matched CIBMTR controls. However, median follow up in that trial was 24 months after ASCT, and the questions of second cancer incidence and other infections in a this population remain (Alvarnas et al, ASH 2014). Herein we report the long term outcomes of ASCT in HIV-infected patients. Methods: Retrospective cohort trial of 52 HIV-infected patients who underwent ASCT for high-risk NHL at City of Hope from January 1, 1998 to December 31, 2011. Two patients were excluded from the analysis due to early post-transplant mortality: one patient died at day 22 due to multiorgan failure, and another died at day 72 due to relapsed lymphoma. Fifty patients with a minimum survival of 100-days post ASCT were evaluated for long-term outcomes. Estimation of event-free survival (EFS) and overall survival (OS) was computed using Kaplan-Meier curves and the cumulative incidence of relapse was estimated with competing risk of mortality. Results: Median follow up was 5.43 years (range 0.30-14.96 years). Median age at the time of transplantation was 45 years (range 26-64 years of age). Prior to transplant, 23 patients (46%) were in complete remission and 27 (54%) were in partial remission. Most patients had aggressive NHL, with diffuse large B-cell lymphoma (48%) and Burkitt lymphoma (24%) being most common histologies. Other subtypes included Burkitt-like (10%), plasmablastic (10%), follicular lymphoma (2%), and T-cell lymphomas (6%). Nine patients relapsed (18%), at a median time of 97 days (range 54-253 days) post ASCT. Fifteen patients (30%) died; 8 out of 15 (53%) died due to relapse. Opportunistic infections (OI) occurred in 8 patients (16%) at a median of 0.68 years (range 0.17-10.82 years). Types of OI included CMV retinitis (1), HSV/Zoster (1), HPV (1), Candida esophagitis (1) and PJP (3). One patient died from OI (PJP). Seven patients (14%) developed a second primary malignancy (SPM) at median time to SPM of 5.63 years (range 1.02-14.35 years). Type of SPM included treatment-related myelodysplastic syndrome (t-MDS) with progression to acute myelogenous leukemia (AML) (2) observed at 3.2 years and 12.6 years, respectively, after ASCT; squamous cell carcinoma of the tongue (1), and skin cancers, including melanoma (1) at 14.3 years post ASCT, basal cell carcinoma (2) at 5.5 and 5.6 years post ASCT, and squamous cell carcinoma in situ (1) at 1.0 year post ASCT. Two patients died from the t-MDS. Conclusions: Thirty-five of 50 patients (70%) were alive at the time of analysis confirming the efficacy of this procedure. EFS/OS at 1 year and 5 years post ASCT was 78% (95% CI:67.3%-90.4%)/82% (95% CI: 71.9%-93.4%) and 71.4% (95% CI:59.8%-85.3%)/73.3% (95% CI: 61.8%-86.9%), respectively. Relapse of NHL tended to occur early post-transplant. Cumulative incidence of relapse was 18% at 1 year post ASCT (95% CI: 8.8%-29.8%). Development of OI was also seen early post-ASCT. While SPM appeared as late as 14.35 years following ASCT, it was no higher than that seen in the non-HIV ASCT setting. This is the largest single institution study reporting long-term follow up of HIV-positive patients post ASCT for NHL and demonstrating that while SPM remain a long term concern neither SPM, OI or HIV infection were major factors in mortality. Disclosures No relevant conflicts of interest to declare.

Description: Background: ASCT is an effective treatment for patients with high risk NHL. However, relapse rates remain high. Attempts at further dose intensification are limited by regimen-related toxicity especially in older patients. Zevalin as a single agent has showed activity in aggressive Non-Hodgkin’s Lymphoma (NHL). We therefore, devised a novel conditioning regimen (Z-BEAM) combining standard dose Zevalin (0.4mci/kg) with high dose BEAM (BCNU 150mg/m2 day-7,-6, cytarabine 800mg/m2 and etoposide 800mg/m2 day-5 to day-2, and melphalan 140mg/m2 day-1). Herein, we provide an update on the study and also retrospectively compare this new conditioning regimen with conventional high dose BEAM in older patients (age 〉=50). Between 1995 and 2005, 65 patients (BEAM n=32, Z-BEAM n=33) underwent ASCT utilizing these regimens. Patient selection was similar for Z-BEAM and BEAM. Patients received BEAM prior to the opening of the Z-BEAM protocol and similiarly after the Z-BEAM protocol completed accrual. The groups were well matched for most demographics and disease status. Median age: Z-BEAM - 62 yrs (range 50–78), BEAM - 64 yrs (range 50–77); 1st CR/PR pts comprised 45% in the Z-BEAM arm and 34% in the BEAM, 〉 =1st Relapse 42% vs 50% and induction failure 12% vs 15%. (p=0.7). Median number of prior regimens was 3 in the Z-BEAM group vs 2 in the BEAM arm.(p=0.08) 54 % had bulky disease at diagnosis in the Z-BEAM group vs 41% in the BEAM group (p=0.30). Results: Two-year OS was 78% for all pts (95%CI, 67–86). Two-year OS/PFS in the Z-BEAM group was 88%(95% CI, 70–95)/72 %(95% CI, 57–83) respectively vs 65% (95%CI, 48–77)/ 67%( 95CI, 50–79) in the BEAM group (Figure1). Analysis by histology showed that in patients with diffuse large B-cell lymphoma (DLBCL), there was a significant difference in OS/PFS of Z-BEAM vs BEAM, 95% vs 48% at 2 yrs (p=.009)/ 88% vs 48% ( p=0.015). The OS/PFS difference of Z-BEAM vs BEAM in patients with mantle cell lymphoma did not reach significance. The toxicity profile and transplant related mortality was similar in both regimens. Conclusions: Our study suggests that the addition of Zevalin to the BEAM conditioning regimen is feasible and well tolerated in older patients. The favorable outcome of patients treated with Z-BEAM compared with BEAM alone, especially in patients with DLBCL, suggests that prospective study in a randomized trial is warranted. Overall Survival 
 ZBEAM versus BEAM Overall Survival 
 ZBEAM versus BEAM

Description: Abstract 2890 Poster Board II-866 INTRODUCTION: Tanespimycin disrupts Hsp90, a key molecular chaperone for signal transduction proteins critical to myeloma growth, survival, and drug resistance. Increased Hsp70 expression is a pharmacodynamic (PD) marker for Hsp90 inhibition (Modi et al, J Clin Oncol, 2007). Tanespimycin + bortezomib has synergistic antitumor activity and enhanced proteasome inhibition in primary multiple myeloma (MM) cells. Tanespimycin + bortezomib has demonstrated durable responses in patients with relapsed/refractory MM with low rates of neutropenia and peripheral neuropathy (PN) relative to historical data on bortezomib monotherapy. In preclinical studies, tanespimycin protected against bortezomib-induced PN. Here we present PD data and updated efficacy and safety results of this phase 1/2 study of tanespimycin + bortezomib in patients with relapsed/refractory MM. METHODS: Patients with relapsed/refractory MM who had received ≥2 prior regimens were enrolled and received bortezomib (0.7, 1.0, or 1.3 mg/m2) intravenous (IV) bolus followed by a 1-hour infusion of tanespimycin (100, 150, 220, 275, or 340 mg/m2) on days 1, 4, 8, and 11 in each 21-day cycle. Peripheral blood mononuclear cells (PBMCs) were collected and lysates were analyzed for Hsp70 expression and 20S proteasome activity. Hsp70 levels, measured by Western blot, and 20S proteasome activity, measured as composite of chymotrypsin, trypsin, and caspase activity, were measured on days 1 and 11 at 0, 4, and 24 hours postdose and normalized to baseline pretreatment levels in each patient. RESULTS: Seventy-two patients were enrolled with 42 patients treated at the highest doses (340 mg/m2 tanespimycin, 1.3 mg/m2 bortezomib). The median age was 60 years and 72% had IgG subtype. Median time since MM diagnosis was 51 months and the median number of prior regimens was 5 (range 1–15) including stem cell transplant (69%), thalidomide (74%), bortezomib (69%), lenalidomide (28%), and other Hsp90 inhibitors (13%). A total of 78% of patients had a history of PN prior to study entry. In the present study, overall response rates (ORR; minimal response or better by modified EBMT) were 48% in the 21 bortezomib-naive patients, 22% in the 23 bortezomib-pretreated patients, and 13% in the 23 bortezomib-refractory patients. ORR was 64% in bortezomib-naive patients who had '3 prior regimens. The median duration of response was 12 months (n=18 patients), including 3 bortezomib-refractory patients each with durable partial responses (PRs) through months 12, 22, and 27, respectively. Of these 3 bortezomib-refractory patients with long-term responses, 2 patients had progressed while being treated with prior bortezomib (bortezomib/dexamethasone and bortezomib/thalidomide/dexamethasone). Thrombocytopenia occurred in 40% of patients (25% Grade 3/4). In cycle 1, mean platelet counts decreased from 180,000/μL on day 1 to 154,000/μL on day 11. Neutropenia was observed in only 4% of patients (3% Grade 3/4). In cycle 1, mean absolute neutrophil counts (ANC) actually increased from 3.0 × 109/L on day 1 to 4.2 × 109/L on day 11. Grade 1 or 2 PN was observed in 15 patients (21%) and importantly no Grade 3/4 PN was observed. Similarly, no severe constipation or anorexia was observed. Hsp90 inhibition was achieved at tanespimycin doses of 275 mg/m2 (n=3) and 340 mg/m2 (n=15) as exhibited by 1.9-fold and 1.5-fold Hsp70 increases, respectively, from baseline to day 1 hour 4 and 1.7-fold and 2.0-fold Hsp70 increases, respectively, from baseline to day 11 hour 0. Proteasome activity decreased from 100% at baseline to 40%, 54%, 61%, and 53% at day 11 hour 1 with tanespimycin doses of 150 (n=2), 220 (n=3), 275 (n=5), and 340 mg/m2 (n=23), and further decreased to 26%, 36%, 43%, and 34%, respectively, at day 11 hour 24. CONCLUSION: Tanespimycin and bortezomib in combination is well tolerated with a low frequency of PN and neutropenia, which compares favorably with historical data on bortezomib monotherapy. Tanespimycin + bortezomib effectively targets the proteasome (with decreased 20S proteasome activity) and Hsp90 (as reflected by increased Hsp70 expression), and is associated with durable responses in heavily pretreated MM patients. Tanespimycin + bortezomib is currently being tested in a randomized phase 3 clinical trial. Disclosures: Richardson: Millennium and Celgene: Speakers Bureau; Millennium Pharmaceuticals: Research Funding. Off Label Use: Combination uses. Chanan-Khan:Millennium, Celgene, Immunogen: Honoraria, Speakers Bureau. Lonial:Novartis: Consultancy; BMS: Consultancy; Millennium: Consultancy, Research Funding; Celgene: Consultancy; Gloucester: Research Funding. Kopit:Bristol-Myers Squibb,: Employment, Equity Ownership. Berman:Bristol-Myers Squibb: Employment. Anderson:Celgene, Novartis, Millennium, BMS: Honoraria; Celgene, Novartis, Millennium, BMS: Research Funding; Celgene, Novartis, Millennium, BMS: Consultancy.

Description: Introduction: Tandem autologous transplant (auto- auto) has been studied as a method to increase remission rates and reduce relapse in the upfront therapy of MM. The use of autologous followed by reduced intensity conditioning allogenic transplantation (auto-allo) offers the potential of long-term graft-versus-myeloma (GVM) effect, but with the risk of graft versus host disease and potentially higher non-relapse mortality (NRM). Trials comparing these two strategies relied on availability of HLA-matched sibling donors for arm allocation (biological "randomization") and have yielded conflicting results, in part due to trial size or limited follow up. A pooled analysis of multiple trials with extended follow up provides the best opportunity to compare these two transplant strategies. Methods: We obtained individual patient data from participants of 4 trials comparing auto-auto vs. auto-allo after brief induction therapy, namely BMT CTN 0102 (N=709), NMAM2000 (N=357), PETHEMA/GEM2000 (N=110), and the Torino consortium trial (N=162). In all 4 trials arm allocation was by biological "randomization". Patients were designated high risk if beta-2 microglobulin ≥ 4.0 mg/L at diagnosis or presence of deletion of chromosome 13 by metaphase karyotyping. Time to event outcomes were analyzed by intention to treat, from the time of first autologous transplant. Main outcomes analyzed were overall survival (OS) and progression free survival (PFS). Secondary outcomes analyzed were NRM and risk of relapse, treated as competing risks, and post relapse survival. Results: There were 1,338 patients included in the analysis, 899 in auto-auto and 439 in auto-allo. Median follow up of survivors is 118.5 months. Characteristics of the two arms are displayed in Table 1. Median OS was 78.0 months in auto-auto and 98.3 months in auto-allo (HR= 0.85, P=0.003, Figure 1). OS was 59.8 % vs. 62.3% at 5-years (P=0.37) and 36.4% vs. 44.1% at 10 years (P=0.01) for auto-auto and auto-allo respectively. PFS was also improved in auto-allo (HR= 0.84, P=0.004) with 5-year PFS of 23.4 vs. 30.1% (P=0.01) and 10-year PFS of 14.4% vs. 18.7% (P=0.06). For the 214 high risk patients (125 auto-auto, 89 auto-allo) there was superior 5-year and 10-year PFS with auto-allo, but no difference in OS. Risk of NRM was higher in auto-allo (10 year 8.3% vs. 19.7%, P

Description: INTRODUCTION: Pelareorep is the infusible form of human reovirus (RV). Our single-agent phase 1 RV trial in relapsed multiple myeloma (MM) showed that pelareorep treatment selectively infected MM cells, as viral RNA was found in myeloma cells and not the bone marrow (BM) stroma. However, we did not observe apoptosis. Our ongoing phase 1 trial, which combines the proteasome inhibitor carfilzomib with RV, has demonstrated RV infection, apoptosis, and clinical responses. We investigated the molecular mechanisms behind the role of a PI (carfilzomib) in this setting. RESULTS: In all MM cell lines we tested (n=4), independently from their sensitivity to RV infection (Stiff et al., Mol Cancer Ther, 2016), viral replication and apoptosis was impaired when MM cells were directly exposed to PIs (carfilzomib and bortezomib). When this experiment was repeated in the setting of the bone marrow cellular fraction or peripheral blood mononuclear cells (PBMCs), it had the opposite effect, as the addition of PI to RV increased RV replication and apoptosis in MM cells. When we washed PBMCs after overnight exposure to RV+PI or to either single agent, then added MM cells, we observed higher infection and apoptosis in cancer cells co-cultured with RV+PI compared to levels from PBMCs treated with each of the single agents, suggesting that PIs increase the ability of PBMCs to serve as a reservoir for infectious reovirus. Monocytes (CD14+) can engage in phagocytosis of reovirus (Berkeley et al., Cancer Immunol Res, 2018), and accordingly we found that RV genome and capsid protein production were detected in CD14+ cells, but not in CD14-depleted PBMCs, and increased upon PI treatment compared to that in RV-treated CD14+ cells. Given that the NF-κB complex is a key proinflammatory signaling pathway associated with the early innate-antiviral immune response, and because PIs can block the degradation of the NF-κB inhibitor IκBα upon phosphorylation, we investigated the effect of the specific IκBα inhibitor Bay-11 in RV viral replication. Our data show that either PI or Bay-11 can inhibit RV-induced IκBα phosphorylation and its subsequent degradation upon RV infection in CD14+ cells, an effect associated with higher capsid formation in RV-treated CD14+ cells in combination with PI or Bay-11, compared to levels from RV alone. Cytokine profiling in PBMCs and CD14+ cells treated with RV in combination with either PI or Bay-11 showed a significant decrease in IFN-α and IFN-β (IFNs) levels and a concomitant increase in RV replication, in contrast to levels from RV alone (p

Description: Combination tacrolimus and sirolimus graft-versus-host disease (GVHD) prophylaxis for allogeneic transplant in patients conditioned with a fractionated total body irradiation–based regimen has shown encouraging results. We studied this prophylaxis combination in 85 patients receiving a matched-sibling transplant conditioned with 3 different regimens:fludarabine-melphalan (n = 46); total body irradiation–etoposide (n = 28), and busulfan-cyclophosphamide (n = 11). The conditioning regimens were completed on day −4. Sirolimus and tacrolimus were started on day −3 to avoid overlap with conditioning therapy. All patients engrafted, with a median time to neutrophil engraftment of 15 days. The cumulative incidence of acute GVHD grades II to IV and III to IV was 43% and 19%, respectively, with no significant difference by conditioning regimen. The 2-year cumulative incidence of chronic GVHD was 46%. With a median follow-up of 26 months, disease-free survival was 58% and overall survival, 66%. The day-100 and 2-year nonrelapse mortality was 4.8% and 10.2%, respectively. The overall incidence of thrombotic microangiopathy was 19%, and it was significantly higher with busulfan/cyclophosphamide (55%, P = .005). Tacrolimus plus sirolimus is an effective combination for acute GVHD prophylaxis and is associated with very low nonrelapse mortality. Thrombotic microangiopathy is a significant complication with this regimen, particularly in patients receiving busulfan/cyclophosphamide.

Description: Introduction: 18Fluoro-deoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is one of the most widely used imaging techniques to detect multiple myeloma (MM). Intracellular FDG uptake depicts in vivo metabolic activity, which can be seen in both malignant and non-malignant cells, resulting in limited sensitivity and specificity. Our group showed preclinically that tracing MM dissemination using a CD38-directed human antibody, daratumumab, that is radioconjugated with copper-64 via the chelator DOTA (64Cu-DOTA-Dara), led to improved sensitivity and specificity over that of FDG (Caserta et al, Blood 2018). Herein, we report the results of a Phase 1 trial (NCT#03311828) designed to 1) assess the safety and feasibility of 64Cu-DOTA-Dara PET/CT and 2) to evaluate and characterize the ability of 64Cu-DOTA-Dara to accurately detect or exclude MM lesions compared with FDG PET/CT. Methods: Patients with biopsy-proven MM and/or a plasmacytoma received an FDG PET/CT scan within 60 days of enrollment. On Day 0, patients were infused with unlabeled ("cold") Dara at one of four dose levels (0 mg, 10 mg, 45 mg, 95 mg) to optimize biodistribution of radioconjugated 64Cu-DOTA-Dara, especially in the liver and the spleen. Within 6 hours of unlabeled Dara administration, patients received 64Cu-DOTA-Dara at a dose of 13.63-16.68 mCi (~5 mg). Whole-body PET scans were obtained at 24 hours and at 48 hours (the latter scan encompassing known tumors). 64Cu-DOTA-Dara standardized uptake values (SUV) were evaluated in MM lesions and normal organs, which were then compared with values from standard FDG PET/CT. Biopsies were performed on accessible discordant lesions. Results: A total of 10 Dara-naïve patients were imaged. Patients were treated with 0 (n=3), 10 (n=3), 45 (n=3), or 95 mg (n=1) of unlabeled Dara. Four patients had newly diagnosed disease, one had biochemical relapse, one had a recurrent plasmacytoma by MRI, and four had possible recurrence by standard PET/CT. No significant adverse events were observed from either cold or 64Cu-DOTA-Dara. With the exception of the one patient with a recurrent plasmacytoma, radiolabeled antibody was eliminated from systemic circulation in subjects analyzed at the first three dose levels within 30 min post injection. In the patient with a recurrent plasmacytoma, the radiolabeled antibody was elevated in the blood for over two days. One newly diagnosed patient had extensive disease by FDG PET and had a biopsy-proven target lesion in the sternum, which had an SUVmax of 14.7 on 64Cu-DOTA-Dara PET/CT vs. 3.3 onFDG PET/CT. A second biopsy from the same patient was taken from a discordant iliac crest lesion (positive for 64Cu-DOTA-Dara but negative for FDG PET/CT) that showed 20-30% MM cell infiltration. In another patient, an iliac crest lesion was 64Cu-DOTA-Dara positive and FDG-negative; biopsy revealed 6% plasmacytosis in the bone. A third patient had an FDG PET/CT positive pleural lesion with an SUVmax of 8.98 and negative on 64Cu-DOTA-Dara (Figure 1A). The lesion did not show recurrence upon biopsy. Furthermore, 64Cu-DOTA-Dara PET/CT yielded superior imaging of bone lesions in the calvarium (Figure 1B). Escalating doses of unlabeled Dara decreased liver and spleen uptake by 64Cu-DOTA-Dara. Conclusions: In this ongoing study, 64Cu-DOTA-Dara PET/CT imaging is to date safe and provides whole body imaging of MM. Further dose escalation of cold Dara (145 mg, 195 mg) is planned to optimize background interference. This modality has the potential to improve sensitivity and specificity over FDG PET/CT scanning in early-stage MM as well as in recurrent disease. Disclosures Krishnan: Celgene, Janssen, Sanofi, BMS: Consultancy; Sutro BioPharma, zPredicta: Consultancy; Amgen, Takeda: Speakers Bureau; Celgene, Z Predicta: Other: Stock Ownership; Takeda: Research Funding. Palmer:Gilead Sciences: Consultancy. Rosenzweig:Celgene, Takeda: Speakers Bureau. Wu:ImaginAb, Inc.: Consultancy, Other: Board Member.