Abstract: Autologous stem cell transplantation without transfusion support in patients with myeloma patients is safe and feasible using a specialized protocol aimed at minimizing blood loss and optimizing supportive care. Moreover, it can yield similar engraftment and survival parameters comparable to those achieved with autologous stem cell transplantation performed with transfusion support.

Abstract: Methods: As reported previously, PVX-410 Multi-Peptide Vaccine (OncoPep, Inc.) is being developed for the treatment of SMM. PVX-410 consists of 4 human leukocyte antigen-A2 (HLA-A2), synthetic 9-mer peptides from unique regions of 3 multiple myeloma (MM)-associated antigens (XBP1 US184-192; XBP1 SP367-375; CD138260-268; and CS1239-247) emulsified in Montanide® ISA-720 VG (Seppic). Adults with SMM at high risk of progression to active MM and were HLA-A2-positive were eligible. The primary objective of this study was to determine the tolerability of PVX-410, initially as monotherapy. Immune response and change in M protein and free light chain ratio (FLC) were also assessed. PVX-410 alone was safe and immunogenic in the initial 12 patients treated, with all 12 having positive immune response to at least 1peptide, as determined by interferon-gamma enzyme-linked immunosorbent spot (Elispot) and tetramer assays. Given its immunomodulatory properties, it was hypothesized that co-administration of lenalidomide (len; Celgene Corporation) would enhance the T cell-mediated immune response induced by PVX-410. Accordingly, the tolerability, immunogenicity, and anti-MM activity of PVX-410+len was then investigated. Results in the PVX-410 alone cohort were previously reported. In the PVX-410+len cohort, patients received a dose of PVX-410, 0.8mg (0.2mg/peptide / 0.8mg total dose) subcutaneously plus 0.5 mL (1mg) Hiltonol® (poly-ICLC; Oncovir, Inc.) intramuscularly every 2 weeks for a total of 6 doses with 3 standard cycles of len (25 mg orally) on Days 1-21 every 28 days, without dexamethasone. Patients are followed for 12months post-treatment. Blood samples for immune response evaluation are collected at Week 0 (Baseline; pre-dose), 2, 4, and 8 during treatment and at Months 1, 3, 6, 9, and 12 post-treatment. Disease response is assessed at the same time points, except Weeks 0 and 2, using International Myeloma Working Group and modified European Group for Blood and Bone Marrow Transplant criteria. Results: Overall, 22 patients have been enrolled, with ages ranging from 39 to 82 years. Ten patients were enrolled in the PVX-410+len cohort, with 9 evaluable for response. All 10 patients received at least 1 cycle of len; 8 received all 3 cycles; 1 received 1 cycle before discontinuing due to a deviation; and 1 completed 2 cycles as of the cutoff date. One patient had 7 of 21 planned doses held due to neutropenia related to lenalidomide, but resumed the next cycle at a reduced dose (from 25 mg to 20 mg). Immunogenicity data with PVX-410+len and PVX-410 alone, as determined via intracellular cytokine staining and tetramer analysis, will be presented. With PVX-410 alone, 5 patients, 2 of 3 with the low-dose of 0.4 mg (0.1mg/peptide) and 3 of 9 at the target-dose (0.2 mg/peptide), experienced progression to active disease within 9 months post-treatment, and 7 had stable disease (SD) at the last follow up visit in the 12 month follow up period. With PVX-410+len, 5 patients have experienced partial or minimal responses and 3 have experienced SD. Durability of response is assessed through the 12-month study period; 1 patient has progressed to active myeloma during this time. PVX-410 was well-tolerated alone and with len. Most adverse events (AEs) have been ≤Grade 2 and non-serious. AEs seen more frequently with PVX-410+len versus PVX-410 alone are expected with len and include hematologic abnormalities (neutropenia, anemia, thrombocytopenia), gastrointestinal disorders (nausea, diarrhea, constipation), skin and cutaneous disorders (rash, pruritus), and myalgia. There was 1serious AE in the combination cohort (pneumonia), considered possibly related to len and unrelated to PVX-410. Conclusions: Six doses of PVX-410 were well tolerated in 22 patients with SMM. Additional AEs seen with PVX-410+len versus PVX-410 alone were expected with the addition of len to the treatment regimen. An immune response to the vaccine was seen in all patients treated with PVX-410 alone and is expected to be enhanced with PVX-410+len; these data will be presented. Based on the promising findings to date, an evaluation of PVX-410 in combination with an antibody to the programmed cell-death-1-ligand complex (PD1/PDL1) is planned to begin in 2015. Disclosures Nooka: Spectrum Pharmaceuticals: Consultancy; Onyx Pharmaceuticals: Consultancy. Off Label Use: Off label use of lenalidomide. Wang:Janssen: Honoraria; Pharmacyclics, Janssen, Celgene, Oncopep, Kite, Juno: Research Funding. Thomas:Novartis, Celgene, Acerta Pharmaceuticals, Idera Pharmaceuticals: Research Funding. O'Donnell:Millennium: Consultancy. Shah:Millenium: Research Funding; Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Array: Research Funding; Bristol-Myers Squibb: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees. Kaufman:Milleniumm, Celgene, Novartis, Onyx, Spectrum: Consultancy. Lonial:Onyx: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Millennium: Consultancy, Research Funding. Richardson:Gentium S.p.A.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium Takeda: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees. Raje:Takeda: Consultancy; BMS: Consultancy; Celgene Corporation: Consultancy; Amgen: Consultancy; Onyx: Consultancy; AstraZeneca: Research Funding; Millenium: Consultancy; Novartis: Consultancy; Acetylon: Research Funding; Eli Lilly: Research Funding.

Abstract: Introduction: PVX-410 Multi-Peptide Vaccine (OncoPep, Inc.) is being developed for the treatment of SMM. PVX-410 consists of 4 human leukocyte antigen-A2 (HLA-A2), synthetic 9-mer peptides from unique regions of 3 multiple myeloma (MM)-associated antigens (XBP1 US184-192; XBP1 SP367-375; CD138260-268; and CS1239-247) emulsified in Montanide® ISA-720 VG (Seppic). Adults with SMM at high risk of progression to active MM who were HLA-A2-positive were eligible. The primary objective was to determine the tolerability of PVX-410, initially as monotherapy and then in combination with lenalidomide (len). Immune and disease response also were assessed. Methods: All patients received 6 bi-weekly subcutaneous injections of PVX-410, initially at the low-dose of 0.4 mg (0.1 mg/peptide or 0.4 mg total) and then at the target dose of 0.8 mg (0.2 mg/peptide or 0.8 mg total). In the PVX-410+len cohort, patients received 3 standard cycles of len (25 mg orally on Days 1-21 every 28 days, without dexamethasone). All patients also received 0.5 mL (1 mg) Hiltonol® (poly-ICLC) (2 mg/mL) via intramuscular injection at the time of PVX-410 administration. Patients were followed for 12 months post-treatment. Blood samples for immune response evaluation were collected at Week 0 (Baseline; pre-dose), 2, 4, and 8 weeks during treatment and at Months 1, 3, 6, 9, and 12 post-treatment. Disease response was assessed at the same time points, except Weeks 0 and 2, using International Myeloma Working Group and modified European Group for Blood and Bone Marrow Transplant criteria. Results: Overall, 22 patients with high-risk SMM were enrolled (age range 39 to 82 years), of whom 12 received PVX-410 monotherapy (3 low-dose; 9 target dose) and 10 received PVX-410 (target dose) + len. All 22 patients have either completed the study through post-treatment Month 12 (N=15) or discontinued before that time (N=7). PVX-410 was well-tolerated, with a treatment-emergent adverse event (TEAE) profile consistent with that expected, based on previous clinical studies with peptide vaccines. All (100%) 22 patients experienced at least 1 TEAE. Among monotherapy patients, the most common TEAEs were injection site pain (50%); fatigue (33%); and injection site erythema, pyrexia, and rash (each 25%). The TEAE profile of PVX-410+len was generally similar to that see with PVX-410 alone, although the incidence of commonly reported TEAEs was higher with the combination than with PVX-410 alone. The majority of TEAEs were Grade 1 in intensity and occurred within 2 days after study vaccine injection. No deaths or study drug-related serious adverse events were reported. PVX-410 was immunogenic as monotherapy (10/11 patients) and in combination with len (9/9), as demonstrated by an increase in the percentage of tetramer+ cells (≥1.5-fold increase over baseline) and interferon-gamma+ (IFN-γ) cells (≥2.0-fold increase over baseline) in the CD3+CD8+ cell population. This increase was statistically higher for IFN-γ+ cells after 2 vaccinations in the combination group. The CD8+ T-lymphocyte response was also characterized by increases from baseline in interleukin-2-, tumor necrosis factor-alpha-, and CD137-positive cells in both treatment groups. Furthermore, decreases in the naïve memory cell population and increases in the effector memory cell population were seen post-vaccination; this response was enhanced by the addition of len. Among the 12 monotherapy patients, 5 (2 low-dose; 3 target-dose) experienced progression to active disease within 9 months post-treatment, and 7 had stable disease (SD) at follow-up Month 12. Among the 9 evaluable PVX-410+len patients, 5 achieved at least a minimal response, with 1 patient achieving a partial response; 1 of these 5 patients then progressed to MM by Month 5 post-treatment. Four patients had SD at follow-up Month 12. Conclusions: Six doses of PVX-410 were well tolerated in 22 patients with high-risk SMM, with an expected AE profile both as monotherapy and in combination with len. An immune response to PVX-410 was seen with PVX-410 alone, which was enhanced by the addition of len. Based on these promising findings to date, investigation of PVX-410 in combination with immunogenic agents is continuing. Disclosures Nooka: Spectrum, Novartis, Onyx pharmaceuticals: Consultancy. Wang:Acerta: Consultancy, Research Funding; Asana biosciences, Beigene, Celgene, Juno, Kite, Onyx, Pharmacyclics: Research Funding; BeiGene: Research Funding; Juno Therapeutics: Research Funding; Kite Pharma: Research Funding; Dava Oncology: Honoraria; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Asana BioSciences: Research Funding. Kaufman:Incyte: Consultancy; Pharmacyclics: Consultancy; Celgene: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Peterkin:OncoPep: Employment. Lonial:Celgene: Consultancy; Onyx: Consultancy; Janssen: Consultancy; BMS: Consultancy; Onyx: Consultancy; Celgene: Consultancy; Novartis: Consultancy; Novartis: Consultancy; BMS: Consultancy; Janssen: Consultancy; Merck: Consultancy; Millenium: Consultancy. Richardson:Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees. Raje:Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Merck: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Research Funding; Eli Lilly: Research Funding.

Abstract: 8032 Background: Patients (pts) with TCE RRMM have few treatment (Tx) options and poor HRQoL. Ide-cel, the first in class CAR T cell Tx for pts with TCE RRMM, improved PFS versus standard (std) regimens in the KarMMa-3 trial. We report the PRO results comparing the Tx arms. PROs provide further understanding of Tx benefit of ide-cel from the pts’ perspective. Methods: KarMMa-3 (NCT03651128) is an open-label phase 3 RCT comparing the efficacy and safety of ide-cel with std regimens in pts with TCE RRMM, who had received 2–4 prior regimens. In addition to clinical endpoints, we evaluated the impact of ide-cel compared with std regimens on the changes in HRQoL, measured by the EORTC QLQ-C30, EORTC QLQ-MY20, and the EQ-5D-5L questionnaires. PROs were collected at baseline (screening), day of infusion and monthly from 2–24 months (mo) and thereafter every 3 mo. This interim analysis reports PROs through 20 mo. Comparisons were performed on least squares mean (LSM) changes from baseline over time between arms using constrained longitudinal data analysis (cLDA). Results: In total, 386 pts were randomized (ide-cel, 254; std regimens, 132). PRO compliance was high over time ( 〉 80%). At baseline, PROs were similar between arms. LSM changes from baseline to 20 mo showed significant differences ( P 〈 0.05), with effect sizes of 0.3–0.7, in favor of ide-cel for most domains, including global health status/QoL, cognitive functioning, fatigue, and pain (EORTC QLQ-C30); side effects of Tx (EORTC QLQ-MY20); and the EQ-5D-5L VAS. The difference in overall LSM change reached or exceeded the pre-specified between-groups minimal importance difference (MID) for improvement in most domains in favor of ide-cel (Table). Conclusions: Ide-cel showed statistically significant and clinically meaningful improvements in HRQoL, including key MM symptoms and functioning, for pts with TCE RRMM compared with std regimens. The PRO data for ide-cel expands upon the clinical outcomes observed in the KarMMa-3 trial. Clinical trial information: NCT03651128 . [Table: see text]

Abstract: Introduction: The standard of treatment for SMM is watchful waiting. PVX-410 (OncoPep, Inc.) is being developed for the treatment of SMM to stop progression to active MM. Methods: PVX-410 consists of 4 HLA-A2 restricted, synthetic 9-mer peptides from unique regions of 3 multiple myeloma (MM)-associated antigens (XBP1 US184-192; XBP1 SP367-375; CD138260-268; and CS1239-247) emulsified in Montanide® ISA-720 VG (Seppic, Inc.). Adults with SMM at high risk of progression to active MM (ie, ≥2 of the following risk factors: serum monoclonal [M]-protein ≥3 g/dL; bone marrow clonal plasma cells 〉 10%; and/or abnormal serum free light chain ratio [0.26-1.65]) and HLA-A2+were eligible. The primary objective of this study phase was to determine the tolerability of PVX-410 as a single agent. Immune response to PVX-410 and change in M protein were also assessed. This ongoing study is similarly evaluating PVX-410 co-administered with lenalidomide (Celgene Corp.). Patients received 6 doses of PVX-410 subcutaneously plus 0.5 mL (1 mg) Hiltonol®(poly-ICLC, Oncovir, Inc.) intramuscularly over 10 weeks. Patients initially received PVX-410 0.4 mg (3 patients, 0.1 mg/peptide / 0.4 mg total dose; low-dose) with escalation to 0.8 mg (9 patients, 0.2 mg/peptide / 0.8 mg total dose; target-dose). Patients were followed for 12 months post-treatment. Blood for immune response evaluation is collected at Week 0 (Baseline; pre-dose), 2, 4, and 8 during treatment and at Months 1, 3, 6, 9, and 12 post-treatment; disease response is assessed at the same timepoints, except Weeks 0 and 2. Immune response to PVX-410 was determined by interferon-gamma (IFN-γ) enzyme-linked immunosorbent spot (ELISPOT) and multimer assays. Samples were tested for IFN-γ production in response to peptide stimulation using ELISPOT and analyzed according to the distribution free sampling (DFR) method (Moodie et al, 2010). A positive (+) response was defined as 1) DFR+ at the timepoint (p-value ≤0.05); and 2) 〉 2-fold increase from Baseline. A result also was considered + if the Baseline value was negative and the post-dose value was DFR+. For determination of peptide-specific memory CD8+ T cell responses, a flow cytometry-based major histocompatibility complex (MHC) multimer assay was performed using tetramers specific for HLA-A2 and each of the 4 peptides. A + response was defined as a value ≥2 X the negative control; ≥Baseline; or, if the negative control or Baseline value was 0.0 or 0.1, the patient result was ≥0.03. Results: Twelve patients were enrolled (3 low-dose; 9 target-dose). Ten subjects were male and all were white. Median age was 56 years. Median time since diagnosis was 0.8 years (range 0.3 to 7.3 years); time since diagnosis was 〈 1 year for 8 patients. All patients had at least 2, and 6 had all 3 high-risk factors. Results are available for all 12 patients through at least 1 month post-treatment. All 12 patients had a positive immune response to at least 1 peptide, as measured by IFN-γ ELISPOT: XBP1 US184-192 (9/12); XBP1 SP367-375 (8/12); CD138260-268 (5/12); and CS1239-247(2/9). DFR-positivity to 1, 2, 3, and all 4 peptides was seen in 5, 3, 3, and 1 patient, respectively. The multimer assay was performed for 9 patients, of whom 7 had vaccine-induced, peptide-specific memory CD8+ T cells: XBP1 US184-192 (7/9); XBP1 SP367-375 (4/9); CD138260-268 (2/9); and CS1239-247(1/9). Five subjects, 2 of 3 in the low-dose and 3 of 9 in the target-dose cohorts, experienced progression to active disease within 9 months post-treatment. Seven patients had stable disease at last follow-up (median follow up of 9 months). PVX-410 was well-tolerated. All adverse events (AEs) were ≤Grade 2 and non-serious. Study vaccine-related AEs generally occurred within the first 2 days post-dose and consisted of systemic symptoms and local reactions commonly seen with vaccines (eg, fever, chills, fatigue, nausea, and other flu-like symptoms / localized erythema, induration, pain, rash, and pruritus). Conclusions: Six doses of PVX-410 were well tolerated in 12 patients with SMM. All 12 patients showed an immune response to the vaccine, with 4 having an immune response to ≥3 of 4 peptides. Based on these promising findings, PVX-410 is being investigated in combination with 3 cycles of fixed-dose lenalidomide. Given its immunomodulatory properties, it is hypothesized that co-administration of lenalidomide will enhance the T cell-mediated immune response induced by PVX-410. Disclosures Thomas: Novartis, Celgene, Millenium, Idera Pharmaceuticals: Consultancy, Research Funding. Weber:OncPep: Research Funding. Kaufman:Millennium; Celgene; Novartis; Onyx; Janssen; Spectrum: Consultancy; Novartis; Onyx; Merck; Celgene: Research Funding; Millennium; Celgene; Novartis; Onyx; Janssen; Spectrum: Honoraria. Lonial:Millennium, Celgene, Novartis, BMS, Onyx: Consultancy, Research Funding. Raje:Eli Lilly, Acetylon: Research Funding; novartis, Amgen, Celgene, Millenium, Onyx: Consultancy.

Abstract: Background High dose chemotherapy and autologous stem cell transplant (ASCT) results in cure for up to 50% of patients with Hodgkin (HL) and aggressive non-Hodgkin lymphoma (NHL) that relapse after initial treatment with chemo-immunotherapy. Despite improvements in supportive care and patient selection, death after ASCT remains a concern due to progressive disease, infection, and other treatment- and non-treatment-related causes. We evaluated causes and predictors of death in patients undergoing ASCT for HL and NHL. Methods We conducted a single-institution, retrospective study of all patients with HL and NHL including diffuse large B-cell lymphoma, high grade B-cell lymphoma NOS, follicular lymphoma, Burkitt lymphoma, marginal zone lymphoma, and T-Cell lymphoma who underwent ASCT at Emory University between January 1, 2006 and June 1, 2017. We evaluated each patient with regards to pre-transplant disease and other baseline characteristics, treatment response after ASCT, occurrence of relapse post-ASCT, post-ASCT death and cause of death. Among patients who died, we compared baseline characteristics of interest between groups based on the documented cause of death using Fisher's Exact tests and t-tests. The association between cause of death and time to death from ASCT was evaluated by the Kruskal-Wallis test. Box plots were used to describe time to death post-transplant. Results Of 642 patients completing ASCT, 192 died during the period of observation after a median follow-up of 24 months. Among patients who died, the leading causes of death were relapsed disease (n=136, 71%), infection (n=18, 9%), organ dysfunction (n=16, 8%), secondary malignancy (n=8, 4%), and other/unspecified (n-14, 7%). When the group was divided into disease-related (n=136) vs non-disease-related death (n=56), none of the pre-specified variables of interest including age, gender, disease status at transplant, stage, induction or salvage therapy, conditioning regimen, or KPS were significantly associated with disease- vs non-disease-related death. Of the 18 deaths due to infection 7 were due to bacterial sepsis (including 5 prior to day +30 post ASCT), 3 were due to fungal infections, 3 were due to pneumonia, 1 death each was due to hepatitis C, nocardia, pneumocystis jirovecii, cytomegalovirus, and C. Difficile. The median time to death for patients experiencing infection or organ dysfunction was 0.5 years each compared to 1 year for patients dying of disease relapse and 4 years for patients experiencing a secondary malignancy (p 〈 0.001; See Figure). Conclusions Among patients completing ASCT for HL or NHL, most deaths occurred due to relapse of the primary disease. There were no significant associations with baseline or treatment-related variables with the cause of death. The median time to death for patients with infection or organ dysfunction was 0.5 years, suggesting that continued monitoring and supportive care of patients completing ASCT is required beyond the initial engraftment period. Our findings support the role of intensive follow-up during the first year post- ASCT and continued monitoring for long-term toxicities for subsequent years of follow-up. Figure Figure. Disclosures Roberts: AstraZeneca: Consultancy. Flowers:Eastern Cooperative Oncology Group: Research Funding; National Cancer Institute: Research Funding; Gilead: Research Funding; Burroughs Wellcome Fund: Research Funding; V Foundation: Research Funding; OptumRx: Consultancy; Genentech/Roche: Research Funding; Janssen Pharmaceutical: Research Funding; Celgene: Research Funding; Millennium/Takeda: Research Funding; Pharmacyclics: Research Funding; Abbvie: Consultancy, Research Funding; Gilead: Consultancy; Karyopharm: Consultancy; Pharmacyclics/ Janssen: Consultancy; TG Therapeutics: Research Funding; BeiGene: Research Funding; Acerta: Research Funding; Abbvie: Research Funding; Spectrum: Consultancy; Genentech/Roche: Consultancy; Denovo Biopharma: Consultancy; Bayer: Consultancy. Waller:Novartis Pharmaceuticals Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celldex: Research Funding; Kalytera: Consultancy; Pharmacyclics: Other: Travel Expenses, EHA, Research Funding; Cambium Medical Technologies: Consultancy, Equity Ownership. Lonial:Amgen: Research Funding. Allen:Merck: Research Funding; Bayer: Consultancy. Blum:Morphosys: Research Funding; Novartis: Research Funding; Seattle Genetics: Research Funding; Celgene: Research Funding. Kaufman:Roche: Consultancy; Karyopharm: Other: data monitoring committee; Abbvie: Consultancy; Janssen: Consultancy; BMS: Consultancy. Nooka:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Spectrum Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive technologies: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees. Cohen:Bristol-Myers Squibb: Research Funding; Janssen: Research Funding; Bristol-Myers Squibb: Research Funding; Infinity Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Infinity Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Takeda: Research Funding; BioInvent: Consultancy; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BioInvent: Consultancy; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Abstract: Background: High-dose chemotherapy followed by autologous stem cell transplantation (SCT) is the current standard of care for myeloma patients for attaining deeper responses. Generic melphalan formulations that were used for more than half a century were susceptible to several challenges (marginal solubility, limited chemical stability after reconstitution and prone for hydrolysis, requirement of propylene glycol as a co-solvent, etc). Evomela™, a Captisol®-stabilized propylene glycol-free melphalan preparation recently obtained FDA indication for use as a high-dose conditioning treatment prior to SCT in patients with myeloma. However, no comparative data relative to conventional melphalan exists. The objective of our study was to evaluate if Evomela™, a more stable compound, can potentially be delivered at the intended dose and deliver higher response rates relative to melphalan. We also reviewed the safety of Evomela™ compared to the generic formulation in this retrospective analysis. Methods: This is a retrospective analysis comparing 2 sequential cohorts of myeloma patients that underwent autotransplant at a single institution. Our institution switched to Evomela™ on September 15th 2016. Approximately 201 patients received a single autotransplant with Evomela™ from September 15th 2016 until September 14th 2017. The control group (193 patients) received conventional melphalan from September 15th 2015 until September 14th 2016. Both Evomela™ and the conventional melphalan were administered on the same day of transplant with the same amount of infusion time. Patient characteristics, toxicity and responses at day 100 were collected and compared between the 2 groups. Fischer's exact and Cochran-Mantel-Haenszel tests were used to compare responses and toxicities. Results: Median age of the patients is 62 years (range 16-78). Patient and transplant characteristics were summarized in Table 1. Both of the groups are balanced, except for 2 variables. The Evomela™ group had higher rates of patients with CAD and 8% more patients received RVD induction therapy. All of the pre-transplant parameters, conditioning regimens and median CD34+ cells infused were similar. The post-SCT ≥VGPR rate was significantly higher for Evomela™ relative to melphalan (85.3% vs 78%, p=0.043), especially when the ≥VGPR rates prior to SCT were similar across the 2 groups (58.5% vs 56.5%, p=0.381), Fig 1. While the difference is seen for both 200 mg/m2 (63.8% vs 54.8%) as well as 140 mg/m2 (91.9% vs 80.4%), the ∆ change (pre-SCT VGPR to post-SCT VGPR) is highly significant among patients receiving Evomela™ 140 mg/m2 vs melphalan (37.5% to 91.9% for ∆ 54.4% vs 61.7% to 80.4% for ∆ 18.7%, p 〈 0.001). Higher rates of neutropenic fevers were seen in the Evomela™ group (p=0.032) but the safety profile, day 30 transplant related mortality, readmission rates, ICU transfers and cardiac complications were similar to melphalan, as outlined in Table 2. Conclusions: These results suggest that by using Evomela™ the intended dose of the alkylating agent is delivered when compared to the conventional melphalan formula. Considering the similar complication rates and safety profile while obtaining higher and deeper response rates supports the use of Evomela™. Disclosures Kaufman: BMS: Consultancy; Karyopharm: Other: data monitoring committee; Janssen: Consultancy; Abbvie: Consultancy; Roche: Consultancy. Hofmeister:Oncopeptides: 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; Adaptive biotechnologies: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees. Waller:Novartis Pharmaceuticals Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Other: Travel Expenses, EHA, Research Funding; Kalytera: Consultancy; Cambium Medical Technologies: Consultancy, Equity Ownership; Celldex: Research Funding. Heffner:Kite Pharma: Research Funding; Genentech: Research Funding; ADC Therapeutics: Research Funding; Pharmacyclics: Research Funding. Lonial:Amgen: Research Funding. Nooka:GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Spectrum Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive technologies: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees.