Hayman, Suzanne R.

Introduction: Daratumumab (D) is an anti-CD38 monoclonal antibody, used frequently in combination with immunomodulatory drugs (IMiDs), lenalidomide (Len) and pomalidomide (Pom). There are no studies comparing DRd to DPd in Len-exposed or refractory multiple myeloma (MM). We present the Mayo Clinic experience of DPd and DRd utilization and outcomes. Methods: We identified consecutive MM pts who received D, between 1/2015 and 4/2019 at Mayo Clinic. We included pts who were exposed (at least one full cycle, 21/28 days) or refractory (progression on full dose or maintenance Len during treatment or within 60 days of stopping Len) to Len prior to D and received 1 to 4 prior lines of therapy. Only Pts who received DRd and DPd were included. Results: Out of 411 evaluable pts 162 met the inclusion criteria; 67 were Len exposed, but not refractory and 95 were Len refractory. Pts' characteristics are shown in Table 1. DRd was used in 76 (47%) and DPd in 86 (53%) pts. Majority of pts (105; 65%) received DPd or DRd in the 2nd or 3rd line and 104 pts (64%) are still alive. In Len refractory pts, the median time from last dose of Len to D initiation was 1 mths (interquartile range 0-6.5). Seventy pts (43%) had high-risk cytogenetics (HR). Only 11 pts (7%) underwent autologous hematopoietic cell transplant after DPd or DRd regimen. There was no significant difference between pts who received DRd and DPd in terms of age (>65 years), gender, race, proportion exposed or refractory to Bortezomib, number of prior lines of treatment (>2), or HR status (p>0.05 for all). Pts who received DPd were 4 times more likely to be Len refractory compared to pts who received DRd, p=0.0008. Median follow up time for the whole cohort from initial diagnosis was 92 mths (CI 95%; 79.5-107), while from D start date was 30 mths (CI 95%; 27-34). Median PFS for the whole cohort was 21 mths (CI 95%; 15-25) and median OS was 138 mths (CI 95%; 111-193). In Len exposed but not refractory pts, n=67, the overall response rate (ORR) was 82% in the DRd group compared to 68% in the DPd group, p=0.2. There was no difference in median PFS; 25.5 mths (CI 95%; 23-NR) for DRd compared to 25 mths (CI 95%; 5-NR) for DPd, p=0.37. Similarly, there was no difference in median OS for DRd compared to DPd; NR mths (CI 95%; 138-NR) and 145.5 mths (CI 95%; 70-NR), respectively, p=0.06. In the 48 Len exposed but refractory pts who received DRd or DPd in 2nd or 3rd line, there was no difference in median PFS; 39 mths (CI 95%; 23-NR) for DRd compared to 21 mths (CI 95%; 3-NR) for DPd, p=0.11. Similarly, there was no difference in median OS for DRd compared to DPd; NR mths (CI 95%; NR-NR) and 145.5 mths (CI 95%; 36-NR), respectively, p=0.13. In Len refractory pts only, n=95, the ORR was 84% in the DRd group compared to 58% in the DPd group, p=0.009. There was no difference in median PFS; 25 mths (CI 95%; 13-32) for DRd compared to 9 mths (CI 95%; 5-15) for DPd, p=0.18. Similarly, there was no difference in median OS for DRd compared to DPd; 103 mths (CI 95%; 78-NR) and 106 mths (CI 95%; 66-183), respectively, p=0.5. In the 57 Len refractory pts who received DRd or DPd in 2nd or 3rd line, there was no difference in median PFS; 25 mths (CI 95%; 13-32) for DRd compared to 13 mths (CI 95%; 5-NR) for DPd, p=08. Similarly, there was no difference in median OS for DRd compared to DPd; 103 mths (CI 95%; 69-NR) and 105 mths (CI 95%; 47-NR), respectively, p=0.35. In the 16 Len exposed but not refractory pts with HR MM who received DRd or DPd in 2nd or 3rd line, the median PFS was better in the DRd group; 24.4 mths (CI 95%; 12-NR) compared to 3.3 mths (CI 95%; 1.9-27.5) for DPd, p=0.0093. However, there was no difference in median OS for DRd compared to DPd; NR mths (CI 95%; 51-NR) and NR mths (CI 95%; 18-NR), respectively, p=0.13. In the 29 Len refractory pts with HR MM who received DRd or DPd in 2nd or 3rd line, there was no statistically significant difference in median PFS; 18 mths (CI 95%; 6-43) for DRd compared to 6 mths (CI 95%; 4-13) for DPd, p=0.22.Similarly, there was no difference in median OS for DRd compared to DPd; 103 mths (CI 95%; 47-NR) and 53 mths (CI 95%; 26-105), respectively, p=0.2. Conclusions: D+IMiD regimens after prior Len exposure/refractoriness are commonly used in real-world, despite the lack of data from prospective clinical trials. Combining D with IMiDs in Len exposed or refractory pts is efficacious, whether the IMiD is Len or Pom. Our study shows that regardless of prior Len use, DRd is at least equivalent to DPd. Prospective studies should be done to confirm these observations. Disclosures Alhaj Moustafa: Acrotech: Consultancy. Larsen:Janssen Oncology: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kapoor:Janssen: Research Funding; GlaxoSmithKline: Research Funding; Cellectar: Consultancy; Celgene: Honoraria; Amgen: Research Funding; Takeda: Honoraria, Research Funding; Sanofi: Consultancy, Research Funding. Fonseca:Amgen: Consultancy; BMS: Consultancy; Celgene: Consultancy; Takeda: Consultancy; Bayer: Consultancy; Janssen: Consultancy; Novartis: Consultancy; Pharmacyclics: Consultancy; Sanofi: Consultancy; Merck: Consultancy; Juno: Consultancy; Kite: Consultancy; Aduro: Consultancy; OncoTracker: Consultancy, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Consultancy; GSK: Consultancy; AbbVie: Consultancy; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees. Dingli:Karyopharm Therapeutics: Research Funding; Rigel: Consultancy; Bristol Myers Squibb: Research Funding; Millenium: Consultancy; Sanofi-Genzyme: Consultancy; Janssen: Consultancy; Alexion: Consultancy; Apellis: Consultancy. Ailawadhi:Celgene: Honoraria; Amgen: Research Funding; Takeda: Honoraria; Janssen: Research Funding; Pharmacyclics: Research Funding; Cellectar: Research Funding; BMS: Research Funding; Medimmune: Research Funding; Phosplatin: Research Funding.

Background: The combination of a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and dexamethasone is the current standard induction therapy for myeloma. Daratumumab (Dara), a monoclonal antibody directed against CD38, is highly effective in treating myeloma and improves response rates and progression free survival (PFS) when added to PI or IMiD. Ixazomib, lenalidomide and dexamethasone (IRd) is an effective, all oral, induction regimen that has been studied in phase 2 and 3 trials. We designed this trial to examine the feasibility and efficacy of adding daratumumab to the IRd regimen as well as early discontinuation of dexamethasone in two sequential cohorts of patients. Patients and Methods: Patients with previously untreated MM who had measurable disease and adequate organ function were enrolled, irrespective of their autologous stem cell transplant eligibility. The primary objective was to determine the rate of complete response to IRD-Dara combination. A one-stage binomial design was utilized in each cohort independently to test the null hypothesis that the complete response rate is at most 25% against the alternative hypothesis that it is at least 45%, with 89% power and 9% type I error. Treatment involved 28-day cycles consisting of ixazomib 4 mg days 1, 8, 15; lenalidomide 25 mg days 1-21, dexamethasone 40 mg, weekly and Dara 16 mg/kg, weekly for two cycles, every other week during cycles 3-6 and then every 4 weeks thereafter during induction (12-cyles) followed by Dara-ixazomib maintenance (maximum 24 cycles). Cohorts A (n=38) and B (N=40) comprised the study population, with dexamethasone discontinued after two cycles in Cohort B. Results: Baseline demographics and patient disposition are outlined in the table. Among those who have gone off study, 9 and 5 patients, respectively in Cohort A and B went off for progression, while 11 and 8 patients in the respective arms discontinued treatment for an alternative therapy, most frequently a transplant. Responses were rapid and deepened over the duration of treatment as shown in the figure; 32% of patients in Cohort A and 28% of patients in Cohort B achieved a complete response; 29% and 23%, respectively, achieved a marrow minimal residual disease (MRD) negative status. After a median follow up was 31.4 months for Cohort A and 18.2 months for Cohort B, median PFS has not been reached in either cohort. A grade 3 or higher adverse event at least possibly attributed to the study drugs was seen in 58% of patients in Cohort A (hematologic in 47% and non-hematologic in 26%) and 50% of patients in Cohort B (hematologic 43%, non-hematologic 20%). The most common toxicities included fatigue, neutropenia, lymphopenia, peripheral neuropathy and nausea. Stem cells were collected in 30 and 31 patients in Cohorts A and B respectively; median (range) of CD34 cells/kg were 8.5 (2.8, 15.9) x 106and 7.0 (2.9, 12.1) x 106, with plerixafor used in 83% and 94% of patients, respectively, in Cohorts A and B as per our standard of care "on-demand" approach based on blood CD34 count. Conclusion: Dara-IRd is an active regimen in newly diagnosed MM, with high overall rates of response and deep responses that improved over time with therapy. Early discontinuation of dexamethasone does not appear to impact the depth, rate or kinetics of response. The toxicities were manageable, with dose modifications. All patients were able to collect stem cells when required, though majority needed plerixafor. Disclosures Kumar: Amgen: Consultancy, Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments, Research Funding; Kite Pharma: Consultancy, Research Funding; Carsgen: Other, Research Funding; Janssen Oncology: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Cellectar: Other; Dr. Reddy's Laboratories: Honoraria; Takeda: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; AbbVie: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Celgene/BMS: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Merck: Consultancy, Research Funding; Adaptive Biotechnologies: Consultancy; Tenebio: Other, Research Funding; Oncopeptides: Consultancy, Other: Independent Review Committee; IRC member; Genentech/Roche: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Genecentrix: Consultancy; Sanofi: Research Funding; Novartis: Research Funding; MedImmune: Research Funding; Karyopharm: Consultancy; BMS: Consultancy, Research Funding. Kapoor:GlaxoSmithKline: Research Funding; Celgene: Honoraria; Takeda: Honoraria, Research Funding; Amgen: Research Funding; Sanofi: Consultancy, Research Funding; Janssen: Research Funding; Cellectar: Consultancy. Dingli:Apellis: Consultancy; Karyopharm Therapeutics: Research Funding; Janssen: Consultancy; Bristol Myers Squibb: Research Funding; Alexion: Consultancy; Rigel: Consultancy; Millenium: Consultancy; Sanofi-Genzyme: Consultancy. Dispenzieri:Pfizer: Research Funding; Takeda: Research Funding; Alnylam: Research Funding; Janssen: Research Funding; Celgene: Research Funding; Intellia: Research Funding. Gertz:Abbvie: Other; Sanofi: Other; Celgene: Other; Research to Practice: Other; Physicians Education Resource: Other: personal fee; Amgen: Other: personal fee; Medscape: Other: personal fee, Speakers Bureau; Appellis: Other: personal fee; Annexon: Other: personal fee; Alnylam: Other: personal fee; Spectrum: Other: personal fee, Research Funding; Janssen: Other: personal fee; Teva: Speakers Bureau; Aurora Bio: Other; Springer Publishing: Patents & Royalties; Proclara: Other; DAVA oncology: Speakers Bureau; Johnson and Johnson: Speakers Bureau; Ionis/Akcea: Other: personal fee; Prothena: Other: personal fee.

Background: Newly diagnosed patients with AL Amyloidosis are a heterogeneous population, ranging from incidentally found nephrotic syndrome to delayed advanced cardiac disease. For the purposes of trials, patients with the highest-risk disease are often excluded from trial participation. An NT-proBNP of 8500 or higher is the criterion most often used for exclusion from clinical trials due to high rates of early death. It is well documented that overall survival is improving over time, in part due to earlier diagnosis and in part due to more effective therapies. It is our aim to describe outcomes of patients with very high (NT-proBNP >=8500) and advanced stage amyloidosis excluding very high (VH) NT-proBNP. Methods: To address this need, we examined the outcomes of AL patients diagnosed between 1/2012 and 7/2020 and seen at our institution within 90 days of diagnosis. Of the 1290 patients, 291 were seen beyond the 90 day threshold and were thus excluded. Another 170 patients were excluded due to missing biomarkers to calculate stage, leaving 829 patients for our analysis. Thresholds for troponins and BNPs were used according to Muchtar Blood 133(7):2019 to correct for assay used. The vast majority of patients had troponin T measured, and for them the 0.025 mcg/L and the 0.035 mcg/L cut-points were used for the 2012 and 2004 staging systems. A minority of patients did not have troponin T, but rather high sensitivity troponin T (n=129) or troponin I (n=23). For patients with high sensitivity troponin T, cut-points of 41 and 50 ng/L were used, respectively, for the 2012 and 2004 systems, and for patients with troponin I only, a cut-point of 0.1 mcg/L was used for both systems. In the 3 patients with no NT-proBNP but with BNP, 400 and 81 ng/L were used respectively for the 2012 and 2004 systems; otherwise, the 1800 ng/L and 332 ng/L cut-offs were used. A BNP of > 700 ng/L was considered equivalent to NT-proBNP greater than or equal to 8500 ng/L. For the 2012 system, the dFLC of 18 mg/dL was used as a cut-off. Survival estimates were done using the method of Kaplan-Meier, and differences in survival were by determined by Log-Rank. Results: The median age of patients was 65 (range 29, 89), and 65% were male. 148 (17%) of these newly diagnosed patients had a VH (>=8500) NT-proBNP. Patients with VH NT-proBNP were older (67 versus 64 years, p=0.004). Only 4% of the VH NT-proBNP patients received an ASCT in contrast to 34% without VH NT-proBNP. With a median follow-up of 30 months for surviving patients, median OS for VH NT-proBNP patients was 3.3 months in contrast to patients without VH NT-proBNP at 68.4 months (Figure). Breakdown of early death for patients with VH NT-proBNP by stage is shown in Table. Of Mayo 2012 patients staged I, II, III, and IV, the percent of patients with VH NT-proBNP was 0, 3, 20, and 45%. In contrast, for the European modification of the Mayo 2004 system, the percent with VH NT-proBNP by stage was 0, 6, 0, 100 for stages I, II, IIIa, and IIIb, respectively. Among the VH NT-proBNP patients, there was stage discrimination using the Mayo 2012 system (6-month death rates were 17, 45, and 66% for patients with stages II, III, and IV, respectively, p=0.02). In contrast, using the Mayo 2004 system in the patients with VH NT-proBNP, 6-month death rates were 45 and 60% for stage II and IIIb patients, respectively (p= 0.12). Among patients without VH NT-proBNP, rates of death in the first year were 21% including stage I patients whose death rates were well under 10%. Patients without VH NT-proBNP but Mayo 2012 Stage III and IV had 1-year mortalities of 28 and 43% respectively. Using the modified Mayo 2004 system, excluding the VH NT-proBNP 1-year mortality was 19 and 37% for patients with stage II and IIIa, respectively. Discussion: Establishing expected outcomes for the sickest AL amyloidosis patients is a means by which trials can be designed for these patients with an unmet need. Patients with VH NT-proBNP should be considered for specially designed trials, and patients without VH NT-proBNP and advanced stage should be included in trials for newly diagnosed patients regardless of stage as long as there is appropriate stratification. Disclosures Dispenzieri: Janssen: Research Funding; Pfizer: Research Funding; Intellia: Research Funding; Alnylam: Research Funding; Celgene: Research Funding; Takeda: Research Funding. Kumar:AbbVie: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Tenebio: Other, Research Funding; BMS: Consultancy, Research Funding; Sanofi: Research Funding; Carsgen: Other, Research Funding; Amgen: Consultancy, Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments, Research Funding; Oncopeptides: Consultancy, Other: Independent Review Committee; IRC member; Celgene/BMS: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Merck: Consultancy, Research Funding; Takeda: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Janssen Oncology: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Adaptive Biotechnologies: Consultancy; Dr. Reddy's Laboratories: Honoraria; Novartis: Research Funding; MedImmune: Research Funding; Genecentrix: Consultancy; Kite Pharma: Consultancy, Research Funding; Cellectar: Other; Karyopharm: Consultancy; Genentech/Roche: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments. Dingli:Karyopharm Therapeutics: Research Funding; Bristol Myers Squibb: Research Funding; Millenium: Consultancy; Janssen: Consultancy; Alexion: Consultancy; Rigel: Consultancy; Apellis: Consultancy; Sanofi-Genzyme: Consultancy. Kapoor:Celgene: Honoraria; Cellectar: Consultancy; Janssen: Research Funding; Sanofi: Consultancy, Research Funding; Amgen: Research Funding; Takeda: Honoraria, Research Funding; GlaxoSmithKline: Research Funding. Lin:Janssen: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Novartis: Consultancy; Celgene: Consultancy, Research Funding; Bluebird Bio: Consultancy, Research Funding; Juno: Consultancy; Legend BioTech: Consultancy; Merck: Research Funding; Takeda: Research Funding; Gamida Cells: Consultancy; Sorrento: Consultancy, Membership on an entity's Board of Directors or advisory committees; Vineti: Consultancy. Gertz:Springer Publishing: Patents & Royalties; Amyloidosis Foundation: Research Funding; International Waldenstrom Foundation: Research Funding; NCI SPORE MM: Research Funding; Ionis/Akcea: Consultancy; Alnylam: Consultancy; Prothena: Consultancy; Sanofi: Consultancy; Janssen: Consultancy; Spectrum: Consultancy, Research Funding; Annexon: Consultancy; Appellis: Consultancy; Amgen: Consultancy; Medscape: Consultancy, Speakers Bureau; Physicians Education Resource: Consultancy; Data Safety Monitoring board from Abbvie: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy; Johnson and Johnson: Speakers Bureau; DAVA oncology: Speakers Bureau; Advisory Board for Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Advisory Board for Proclara: Membership on an entity's Board of Directors or advisory committees; i3Health: Consultancy.

Introduction: Richter transformation (RT) refers to transformation of chronic lymphocytic leukemia (CLL) to diffuse large B-cell lymphoma (DLBCL) or other aggressive lymphomas. The incidence, clinical characteristics, and outcomes of RT with CNS involvement remain undefined. Methods: Biopsy-confirmed RT diagnosed from 4/1993 to 4/2018 was identified from the Mayo Clinic CLL database. RT cases with CNS involvement were further reviewed, with clinical characteristics, treatment and follow-up data abstracted. Overall survival (OS) was defined as time from CNS involvement to death from any cause and analyzed using the Kaplan-Meier method. Results: Among 204 CLL patients with biopsy-proven RT, 15 patients had documented CNS involvement by imaging (parenchymal n=11, ocular n=1, parenchymal and ocular n=1, leptomeningeal n=1, cranial and spinal nerve roots n=1). Biopsy confirmation of CNS involvement was available in 11 patients. Of these 15 patients, 10 had CNS involvement at initial RT diagnosis, and 5 patients developed CNS involvement at RT progression, with a median time from RT diagnosis to CNS involvement of 14.9 months (range 2.8-41.1). Prior to RT, 11 patients (73.3%) received no treatment for CLL, 3 (53.4%) received chemoimmunotherapy (CIT) only (1-3 lines), and 1 patient (6.7%) received CIT (1 line) and ibrutinib. CLL FISH results were available in 9 patients, with del(17p) in 2, trisomy 12 in 2, del(13q) in 3, and normal results in 2. One patient had TP53 mutation (FISH result unavailable). IgHV mutation status was known in 3 patients and 1 was unmutated. The median time to RT was 4.4 years (range 0-11.4). The median age at RT diagnosis was 70 years (range 59-78), and 9 (60%) were male. The histology of RT was DLBCL in all 15 patients (diagnosed by CNS biopsy in 8 and other biopsies in 7), with GCB subtype in 6 and non-GCB subtype in 3. MYC rearrangement was detected in 4 of 6 patients tested, and 2 of those also had BCL-2 rearrangement (MYC/BCL-2 double hit). Of the 10 patients with CNS involvement at initial RT diagnosis, 4 had isolated CNS involvement (confirmed by brain biopsy [n=2] or vitreous biopsy [n=2]). All 4 patients were treated with high dose (HD) methotrexate (MTX) based regimen, and 3 patients achieved complete remission (CR) and underwent autologous stem cell transplant with continued CR, while 1 patient achieved partial remission and received whole brain radiotherapy (WBRT) at disease progression. Six patients had both systemic and CNS involvement (confirmed by brain biopsy [n=2] or CSF examination [n=2] in 4; the other 2 were diagnosed by imaging). All 6 patients received CNS directed therapy (HD MTX [n=5] or WBRT [n=1]) as well as systemic therapy (R-CHOP [n=5] or HyperCVAD [n=1]), with varied short duration of disease control (Figure 1A). Of the 5 patients who developed CNS involvement at RT progression (after 1-2 lines of therapy including first-line R-CHOP), 2 had isolated CNS involvement (1 was confirmed by CSF examination and the other was by imaging only). Both were treated with HD MTX based regimen, and 1 achieved a durable remission of 2 years but eventually had CNS relapse, while the other had no response and received WBRT with limited benefit. Three patients had both systemic and CNS involvement (2 were confirmed by CSF examination and the other was by imaging only), and all 3 patients were treated with HD MTX based regimen but all had CNS disease progression within 3 months (Figure 1A). The OS after CNS involvement for all 15 RT patients was 9.4 months (95% CI 2.3-19.1). Patients with CNS involvement at initial RT diagnosis had numerically longer OS compared to patients who developed CNS involvement at RT progression (median OS 13.0 vs 4.1 months, P = 0.137; Figure 1B). Patients with isolated CNS involvement had better OS compared to patients with both CNS and systemic involvement (median OS 32.0 vs 5.3 months, P = 0.009; Figure 1C). Three of the 4 patients who only had isolated CNS involvement at the time of RT diagnosis have ongoing long term remission and survival (Figure 1A). Conclusions: In this large series of RT, approximately 1 in 14 patients had CNS involvement. Patients with isolated CNS involvement appeared to have favorable long term outcome; however, RT patients with both systemic and CNS involvement had extremely poor survival. The incidence, molecular characteristics, and optimal management of RT with CNS involvement in the novel agent era warrant future multicenter studies. Disclosures Wang: Incyte: Research Funding; Innocare: Research Funding; Novartis: Research Funding. Parikh:GlaxoSmithKline: Honoraria; Pharmacyclics: Honoraria, Research Funding; AstraZeneca: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; MorphoSys: Research Funding; TG Therapeutics: Research Funding; Merck: Research Funding; AbbVie: Honoraria, Research Funding; Ascentage Pharma: Research Funding; Genentech: Honoraria; Verastem Oncology: Honoraria. Kay:Tolero Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Meyer Squib: Membership on an entity's Board of Directors or advisory committees, Research Funding; Acerta Pharma: Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Research Funding; MEI Pharma: Research Funding; Sunesis: Research Funding; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees; Agios Pharma: Membership on an entity's Board of Directors or advisory committees; Cytomx: Membership on an entity's Board of Directors or advisory committees; Morpho-sys: Membership on an entity's Board of Directors or advisory committees; Rigel: Membership on an entity's Board of Directors or advisory committees; Oncotracker: Membership on an entity's Board of Directors or advisory committees; Dava Oncology: Membership on an entity's Board of Directors or advisory committees; Juno Theraputics: Membership on an entity's Board of Directors or advisory committees. Witzig:AbbVie: Consultancy; MorphSys: Consultancy; Immune Design: Research Funding; Karyopharm Therapeutics: Research Funding; Incyte: Consultancy; Spectrum: Consultancy; Celgene: Consultancy, Research Funding; Acerta: Research Funding. Nowakowski:MorphoSys: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Celgene/BMS: Consultancy, Research Funding; Kite: Consultancy; Denovo: Consultancy; Kymera: Consultancy; Ryvu: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other; Curis: Consultancy; Seattle Genetics: Consultancy; Nanostrings: Research Funding. Ansell:Trillium: Research Funding; AI Therapeutics: Research Funding; Affimed: Research Funding; Regeneron: Research Funding; Takeda: Research Funding; ADC Therapeutics: Research Funding; Seattle Genetics: Research Funding; Bristol Myers Squibb: Research Funding. Kenderian:MorphoSys: Research Funding; Sunesis: Research Funding; Tolero: Research Funding; BMS: Research Funding; Juno: Research Funding; Gilead: Research Funding; Kite: Research Funding; Novartis: Patents & Royalties, Research Funding; Torque: Consultancy; Humanigen: Consultancy, Patents & Royalties, Research Funding; Lentigen: Research Funding; Mettaforge: Patents & Royalties. Ding:DTRM: Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding; Beigene: Membership on an entity's Board of Directors or advisory committees; alexion: Membership on an entity's Board of Directors or advisory committees; MEI Pharma: Membership on an entity's Board of Directors or advisory committees; Octapharma: Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Research Funding; Abbvie: Research Funding.

Introduction Autologous stem cell transplantation (ASCT) has been used for treating multiple myeloma (MM) for over three decades and is generally reserved for patients younger than 65 years of age. The definition of transplant eligible is ill-defined and different centers have different policies to determine which patients are transplant eligible. Some centers have an age cut-off, others use clinical judgment, and some use various frailty scores (a scoring system based on comorbidities and physical and cognitive assessments) aiming to objectively assess transplant eligibility. There are limited data about outcomes in patients ≥ 75 years. Aim To report on outcomes of ASCT in a cohort of patients with MM aged 75 years or older. Methods Retrospective study of all consecutive MM patients aged ≥ 75 years that underwent ASCT at Mayo Clinic, Rochester, Minnesota. Stem cell transplantation at our center is routinely performed as an outpatient, with patients being hospitalized when deemed clinically necessary upon physician review. Results Between October 2005 and March 2020, 46 patients aged 75 years or older, received an ASCT at Mayo Clinic, Rochester. The median hematopoietic stem cell transplantation specific comorbidity index (HCT-CI) was 0 (range 0-6) with 8 patients having HCT-CI of 5 or 6. Median time from diagnosis to ASCT was 6.45 months (IQR 5.2-10.52) and 54% received reduced intensity conditioning with melphalan 140 mg/m2. All patients except one (that was treated with dexamethasone only) received induction with novel agents (listed in table 1) and 6 patients (13%) received doublet induction. All others received triplet induction. 46% of patients completed the ASCT without requiring hospitalization and 54% (n=25) of patients required hospitalization with a median duration of hospital admission of 9 days (IQR 5-13). Reasons for hospitalization included fever or infection (32%), cardiac arrhythmia (36%) and dehydration (32%). Overall response rate was 100% with a complete response seen in 57% of patients and 16 patients achieving MRD negative sCR. Median overall survival and progression free survival for the cohort were 82 months and 33 months, respectively. One patient died within 100 days of transplant representing a 2% 100-day mortality rate. Univariable cox regression model that evaluated the effect of gender, high risk cytogenetics, hemoglobin, renal function and melphalan dose did not detect any variable that was predictive of OS or PFS (Table 3). Conclusions ASCT is efficacious and can be safely delivered in the outpatient setting in carefully screened patients aged 75 or above. An arbitrary cutoff for age should not be used to exclude patients from ASCT, rather a careful assessment of "physiological age" including performance status and co-morbidities is required by an experienced treating team. Disclosures Kumar: Amgen: Consultancy, Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments, Research Funding; Cellectar: Other; Carsgen: Other, Research Funding; Dr. Reddy's Laboratories: Honoraria; Genentech/Roche: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Sanofi: Research Funding; Kite Pharma: Consultancy, Research Funding; Novartis: Research Funding; Celgene/BMS: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Merck: Consultancy, Research Funding; MedImmune: Research Funding; BMS: Consultancy, Research Funding; Tenebio: Other, Research Funding; Karyopharm: Consultancy; AbbVie: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Janssen Oncology: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Takeda: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Genecentrix: Consultancy; Oncopeptides: Consultancy, Other: Independent Review Committee; IRC member; Adaptive Biotechnologies: Consultancy. Dispenzieri:Pfizer: Research Funding; Janssen: Research Funding; Alnylam: Research Funding; Intellia: Research Funding; Takeda: Research Funding; Celgene: Research Funding. Dingli:Bristol Myers Squibb: Research Funding; Rigel: Consultancy; Janssen: Consultancy; Alexion: Consultancy; Karyopharm Therapeutics: Research Funding; Apellis: Consultancy; Sanofi-Genzyme: Consultancy; Millenium: Consultancy. Kapoor:Cellectar: Consultancy; Takeda: Honoraria, Research Funding; Celgene: Honoraria; Amgen: Research Funding; Sanofi: Consultancy, Research Funding; Janssen: Research Funding; GlaxoSmithKline: Research Funding. Gertz:Prothena: Other: personal fee; Medscape: Other: personal fee, Speakers Bureau; Appellis: Other: personal fee; Alnylam: Other: personal fee; Ionis/Akcea: Other: personal fee; Janssen: Other: personal fee; Research to Practice: Other; Sanofi: Other; Teva: Speakers Bureau; Johnson and Johnson: Speakers Bureau; DAVA oncology: Speakers Bureau; Proclara: Other; Springer Publishing: Patents & Royalties; Celgene: Other; Physicians Education Resource: Other: personal fee; Aurora Bio: Other; Amgen: Other: personal fee; Annexon: Other: personal fee; Spectrum: Other: personal fee, Research Funding; Abbvie: Other.

AbstractThree sets of criteria (International Society of Amyloidosis [ISA], Palladini and Kastritis) were independently developed for staging, progression and response criteria to predict renal survival in patients with AL amyloidosis. We evaluated these criteria using a cohort of 495 newly diagnosed AL amyloidosis patients with renal involvement using time to event competing risk analysis at baseline, 3, 6 and 12 months after treatment. Only Palladini and Kastritis had a staging system and both predicted a higher risk of end stage renal disease (ESRD) in the stage III vs stage I patients but only the Palladini model was predictive for stage II patients. At 3 months, risk of ESRD was significantly higher for Palladini and ISA renal progression (hazard ratio [HR] 2.8 [95% CI: 1.5–5.3, p = .001] and 2.5 [CI: 1.4–4.6, p = .004, respectively]), but renal response was not significantly protective; conversely, the risk of ESRD was not significantly higher for the Kastritis renal progression, but was significantly protective for the Kastritis renal responders (HR 0.38 [95% CI: 0.17–0.84], p = .017). Both progression and response with ISA, Palladini and Kastritis criteria were predictive of ESRD at 6 months and 12 months. While the Palladini staging criteria at baseline, and the ISA and Palladini criteria for progression at 3 months performed better than the Kastritis criteria at baseline and 3 months post‐treatment, the Kastritis criteria performed better for response 3 months after treatment. All three sets of criteria performed well at and after 6 months post‐treatment. These differences are important when choosing endpoints for clinical trials.

AbstractInduction therapy for multiple myeloma with bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (d) (VRd) was traditionally administered as bortezomib given twice weekly on a 3 week cycle. A modified schedule of weekly bortezomib has been adopted over time to decrease treatment burden for patients and reduce treatment‐emergent neuropathy. This study evaluates the response rates and outcomes with different schedules of bortezomib in VRd administered for first‐line treatment for patients with newly diagnosed MM (NDMM). We retrospectively analyzed patients treated with upfront VRd from June 30th 2008 to December 31st 2018, for variations of bortezomib administration. Five hundred and fifty‐five (555) NDMM patients met inclusion criteria; median age 63 years and 61% men. Bortezomib was administered twice weekly every 21 days in 43%, once weekly every 21 days in 41% and once weekly every 28 days in 16%. Though peripheral sensory neuropathy was more frequent with twice weekly dosing (P = .002), this group achieved shorter time to best response (P = .01). Weekly every 21‐day treatment saw higher VGPR or better rates (P = .02). However, with median follow up time of 37 months (IQR 22–56), we found no difference in PFS or OS among the groups. While small differences in response rates were found among the varying administration schedules of bortezomib administration, there was no significant effect on PFS or OS. Given that VRd remains a first line standard of care option for newly diagnosed MM, in the absence of a large trial comparing bortezomib dosing schedule modifications, these results are helpful in supporting current practices of once weekly administration.

AbstractIntroductionLittle is known on continued response following completion of therapy in light chain (AL) amyloidosis.MethodsWe studied 373 AL amyloidosis patients who achieved complete response (CR) or very good partial response (VGPR) to first‐line therapy.ResultsBy end of therapy (EOT), 46% of patients achieved a CR and 54% a VGPR. With no further therapy, 17.5% of patients were upstaged from VGPR to CR (delayed CR), with a median of 9 months. Compared with CR and VGPR at EOT, patients with a delayed CR were characterized by higher proportion of t(11;14) and lower rate of trisomies. Autologous stem cell transplant was more frequent in the delayed CR group. Patients with a delayed CR were characterized by minimal residual disease negativity and organ response rates similar to patients with CR at EOT and higher than patients achieving VGPR at EOT. Patients with a delayed CR had a longer PFS/OS compared to patients with CR or VGPR by EOT (median PFS 149 vs 92 vs 52 months, P < .001; 10‐year OS 87% vs 71% vs 56%, P < .001).ConclusionsThis study characterizes delayed CR in AL amyloidosis, highlights its prognostic impact which is at least similar to those who achieved CR at EOT, and underlines another aspect of response monitoring.

Introduction: In 2017, a two-dose recombinant zoster vaccine (RZV) containing glycoprotein E (gE) and a novel adjuvant was approved to prevent herpes zoster and its complications in adults ≥50 years of age in the US. There are limited data on the immunogenicity and safety of RZV in patients with chronic lymphocytic leukemia (CLL). Methods: Between 8/15/2018 and 11/4/2019, RZV-naïve patients with CLL and monoclonal B-cell lymphocytosis (MBL) seen at Mayo Clinic, Rochester, MN were enrolled in this IRB-approved study. All participants received two doses of vaccine, at 0 and 2 months after enrollment. Cell-mediated immunity was measured by dual-color interferon γ (IFN- γ) and interleukin 2 (IL-2) FLUOROSpot in peripheral blood mononuclear cells (PBMC) after depletion of ≥50% leukemic B cells. Results were reported in spot forming cells (SFC)/106 PBMC in wells stimulated with gE overlapping peptides or varicella zoster virus (VZV) inactivated cell lysate. Response rate was defined as the proportion of participants who achieved a ≥2-fold increase in IFN- γ or IL-2 SFC/106 PBMC one month after the second dose of vaccine compared with pre-vaccination baseline levels. We also determined the geometric mean fold rise (GMFR) and geometric mean count (GMC) of SFC /106 PBMC at baseline and 90 days after the first dose of vaccine. Two cohorts were enrolled: Cohort 1 consisted of individuals with previously untreated MBL and CLL; and Cohort 2 consisted of CLL participants who were on Bruton tyrosine kinase inhibitor (BTKi) therapy. We compared the response data to historic age-and sex-matched healthy controls who received RZV. Chi-square or Fisher's exact tests measured differences in response rates and Kruskall-Wallis tested for differences in continuous variables. Among CLL participants, multivariable regression analysis was used to investigate the association between day 90 SFC and prior BTKi treatment, accounting for age at RZV, age at CLL diagnosis, sex, and day 0 SFC. Results: Sixty-one participants were enrolled. Paired samples were available for 41 participants (22 in Cohort 1 and 19 [18 ibrutinib and 1 acalabrutinib] in Cohort 2), and 68 age- and sex-matched healthy controls. Baseline characteristics of MBL/CLL participants are shown in Table 1. Compared to healthy controls, participants with MBL/CLL had a significantly lower IFN-γ VZV-specific response rate (41% vs. 63%, p=0.03) and IFN-γ gE-specific response (56% vs. 96%, p&lt;0.001); although there were no differences in IL-2 response rates to VZV (51% vs 68%, p=0.09) or gE (95% vs. 100%, p=0.14, Table 2). There were differences in GMFR between participants with MBL/CLL and controls that reached statistical significance for IFN-γ and IL-2 gE-specific responses and borderline significance for IFN-γ VZV-specific responses (Table 2). VZV-specific response rates did not significantly differ between individuals with untreated MBL/CLL and those receiving BTKi (52% vs. 28%, p=0.12 for IFN- γ; (62% vs. 39%, p=0.15 for IL-2), nor did IL-2 gE-specific responses (96% vs. 95%, p=1.0). However, untreated MBL/CLL participants had significantly higher IFN- γ gE-specific response rate compared to BTKi-treated individuals (73% vs. 37%, p=0.02, Table 2). IFN- γ and IL-2 VZV- and gE-specific SFC GMC was significantly higher at Day 90 compared to Day 0 in all vaccinees, although the magnitude of response was significantly lower in MBL/CLL participants compared to healthy controls (Table 3). Among participants with MBL/CLL, age at diagnosis, age at receipt of RZV, and sex did not predict response to vaccination after accounting for prevaccination values. No serious adverse events were noted among MBL/CLL participants while on this study. Additional analyses including determination of humoral immunogenicity and long-term follow up to ascertain risk of herpes zoster infection are ongoing at this time. Conclusion: RZV was associated with lower cell mediated immunogenicity in MBL/CLL participants compared to healthy older adults. Among individuals with CLL, BTKi treatment was associated with decreased cell mediated immunogenicity of the vaccine. Given the inferior response rates, an additional dose of RZV may be considered to boost responses and should be studied in this patient population. Disclosures Johnson: GSK: Research Funding. Ding:Abbvie: Research Funding; Astra Zeneca: Research Funding; DTRM: Research Funding; alexion: Membership on an entity's Board of Directors or advisory committees; MEI Pharma: Membership on an entity's Board of Directors or advisory committees; Octapharma: Membership on an entity's Board of Directors or advisory committees; Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding; Beigene: Membership on an entity's Board of Directors or advisory committees. Kenderian:Humanigen: Consultancy, Patents & Royalties, Research Funding; Torque: Consultancy; Novartis: Patents & Royalties, Research Funding; Kite: Research Funding; Gilead: Research Funding; Juno: Research Funding; BMS: Research Funding; Tolero: Research Funding; Mettaforge: Patents & Royalties; Lentigen: Research Funding; MorphoSys: Research Funding; Sunesis: Research Funding. Wang:Novartis: Research Funding; Incyte: Research Funding; Innocare: Research Funding. Kay:Juno Theraputics: Membership on an entity's Board of Directors or advisory committees; Oncotracker: Membership on an entity's Board of Directors or advisory committees; Dava Oncology: Membership on an entity's Board of Directors or advisory committees; Rigel: Membership on an entity's Board of Directors or advisory committees; Morpho-sys: Membership on an entity's Board of Directors or advisory committees; Cytomx: Membership on an entity's Board of Directors or advisory committees; Agios Pharma: Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees; Sunesis: Research Funding; Abbvie: Research Funding; MEI Pharma: Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Acerta Pharma: Research Funding; Tolero Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Meyer Squib: Membership on an entity's Board of Directors or advisory committees, Research Funding. Levin:GSK: Research Funding. Kennedy:ICW Ventures: Research Funding. Weinberg:GSK: Research Funding. Parikh:GlaxoSmithKline: Honoraria; AstraZeneca: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; TG Therapeutics: Research Funding; Merck: Research Funding; AbbVie: Honoraria, Research Funding; MorphoSys: Research Funding; Verastem Oncology: Honoraria; Pharmacyclics: Honoraria, Research Funding; Genentech: Honoraria; Ascentage Pharma: Research Funding.

Background: Oncolytic virotherapy is a novel immunomodulatory therapeutic approach for relapsed refractory hematologic malignancies. The Indiana strain of Vesicular Stomatitis Virus (VSV) has been engineered to encode interferon beta (IFNβ) and sodium iodine symporter (NIS) to produce VSV-IFNβ-NIS. The virally encoded IFNβ serves as an index of viral proliferation and enhances host anti-tumor immunity. The NIS is inserted as a reporter gene into the viral genome to enable noninvasive monitoring of viral spread using PET/CT imaging. Here we present results of Arm A (patients with low tumor burden) of the Phase I clinical trial (NCT03017820) of intravenous administration of VSV-IFNβ-NIS for patients (pts) with relapsed refractory hematological malignancies: MM, AML, and TCL. Methods: This was a classical 3+3 phase I trial, starting at 5x10^9 TCID50 (50% tissue culture infectious dose) level 1 through 1.7x10^11 TCID50 dose level 4 given as a single IV dose. The primary objective was determining the maximum tolerated dose of VSV-IFNβ-NIS alone; secondary objectives include estimating the safety profile and preliminary efficacy. Correlative objectives include monitoring the pharmacodynamics of viral replication through SPECT/CT imaging with NIS gene, viremia, virus shedding and changes in the immune profile of peripheral blood leukocytes. Adverse events (AEs) are reported based on CTCAE v4; cytokine release syndrome (CRS) grading was based on Lee (Blood 2014; 124(2):188-195) criteria. Results: From April 2017, 12 pts have received IV VSV-IFNβ-NIS in Arm A: MM (7), TCL(4) and AML(1); 3 pts were treated at each dose level (DL) 1 to 4. At DL1, there were five grade 3 hematologic AEs (leukopenia [1], neutropenia [1], lymphopenia [3]) and no grade 3+ non-hematologic AEs. At DL2, three grade 3 hematologic AEs (anemia [2], lymphopenia [1]), four grade 4 hematologic AEs (neutropenia [1], leukopenia [1], lymphopenia [1] and thrombocytopenia [1]). There was 1 event of grade 2 CRS at DL2, two grade 3 non-hematologic AEs (nausea [1], dehydration [1]). At DL3, there was one grade 4 hematologic AE (neutropenia [1]), three grade 3 hematologic AEs (lymphopenia [2], leukopenia [1]), and one grade 3 non-hematologic AE (vasovagal reaction [1]). One grade 2 and grade 1 CRS by Lee criteria were observed. At DL4, there were three grade 3 hematologic AEs (lymphopenia [1], neutropenia [1], thrombocytopenia [1]), and three grade 3 non-hematologic AEs (AST increase [1], skin infection [1], soft tissue infection [1])and two grade 2 CRS. There were no dose limiting toxicities. There was one partial response (DL2) and one complete response (DL4); 3 pts had stable disease, 7 pts progressed. The MM pts receiving VSV-IFNβ-NIS at DL4 had stable disease. Six of the 7 MM pts demonstrated transient reduction in serum level of involved free light chain (LC) after VSV-IFNβ-NIS infusion, with median 20.4% reduction of the involved LC within 48 hrs. Viremia was detectable in all pts at the end of infusion, to varying levels at 30 mins, 1, 2, 4, 24, 48h or 72 hrs post infusion. No persistent viremia was observed. No infectious virus was recovered in buccal swabs or urine and neutralizing anti-VSV antibodies were present by day 29. The IFN levels were detectable within 30 minutes of infusion and peaked between 4 and 48 hrs. The pts with a diagnosis of TCL mounted higher hIFNβ levels within 48 hrs. Remarkably, the TCL pt with CR (DL4) mounted a peak hIFNβ response of 18213.3pg/ml at 48 hrs post infusion, approximately 15-fold higher than any other pt enrolled in the study; and highest neutralizing antibody titer (1:40960). Conclusion: VSV-IFNβ-NIS can be safely administered by intravenous infusion in pts with hematological malignancies, up to a dose level of 1.7 x 1011 TCID50, without dose limiting toxicities and no CRS higher than grade 2. In this small phase 1 study, pts with T-cell lymphoma demonstrated the strongest signal of response, with one confirmed partial response at DL2 and one complete response at DL4. IFNβ is an early biomarker of tumor susceptibility; the magnitude of IFNβ elevation appears to correlate with treatment response. There were no confirmed responses in pts with MM, but the 20.4% transient reduction in LC suggests that combination strategies with VSV-IFNβ-NIS may result in deeper and sustained responses in MM. Future trials investigating combination strategies with immune modulatory drugs are being planned. Disclosures Peng: Imanis: Other: Equity Ownership. Witzig:Karyopharm Therapeutics: Research Funding; Immune Design: Research Funding; Spectrum: Consultancy; Incyte: Consultancy; Acerta: Research Funding; MorphSys: Consultancy; AbbVie: Consultancy; Celgene: Consultancy, Research Funding. Dispenzieri:Intellia: Research Funding; Pfizer: Research Funding; Takeda: Research Funding; Alnylam: Research Funding; Janssen: Research Funding; Celgene: Research Funding. Gertz:Celgene: Consultancy; Annexon: Consultancy; Sanofi: Consultancy; Appellis: Consultancy; Amgen: Consultancy; Medscape: Consultancy, Speakers Bureau; Physicians Education Resource: Consultancy; Data Safety Monitoring board from Abbvie: Membership on an entity's Board of Directors or advisory committees; NCI SPORE MM: Research Funding; Johnson and Johnson: Speakers Bureau; Springer Publishing: Patents & Royalties; Amyloidosis Foundation: Research Funding; Advisory Board for Proclara: Membership on an entity's Board of Directors or advisory committees; Alnylam: Consultancy; Ionis/Akcea: Consultancy; Spectrum: Consultancy, Research Funding; Prothena: Consultancy; DAVA oncology: Speakers Bureau; i3Health: Consultancy; Advisory Board for Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; International Waldenstrom Foundation: Research Funding. Dingli:Rigel: Consultancy; Bristol Myers Squibb: Research Funding; Janssen: Consultancy; Alexion: Consultancy; Apellis: Consultancy; Karyopharm Therapeutics: Research Funding; Millenium: Consultancy; Sanofi-Genzyme: Consultancy. Kapoor:Cellectar: Consultancy; Celgene: Honoraria; Janssen: Research Funding; Sanofi: Consultancy, Research Funding; Amgen: Research Funding; Takeda: Honoraria, Research Funding; GlaxoSmithKline: Research Funding. Lin:Janssen: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Legend BioTech: Consultancy; Juno: Consultancy; Bluebird Bio: Consultancy, Research Funding; Novartis: Consultancy; Celgene: Consultancy, Research Funding; Merck: Research Funding; Takeda: Research Funding; Gamida Cells: Consultancy; Sorrento: Consultancy, Membership on an entity's Board of Directors or advisory committees; Vineti: Consultancy. Kumar:Janssen Oncology: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Cellectar: Other; Carsgen: Other, Research Funding; AbbVie: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Merck: Consultancy, Research Funding; Oncopeptides: Consultancy, Other: Independent Review Committee; IRC member; Sanofi: Research Funding; Dr. Reddy's Laboratories: Honoraria; Adaptive Biotechnologies: Consultancy; Genentech/Roche: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Kite Pharma: Consultancy, Research Funding; Novartis: Research Funding; Celgene/BMS: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; MedImmune: Research Funding; Amgen: Consultancy, Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments, Research Funding; Karyopharm: Consultancy; Takeda: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; BMS: Consultancy, Research Funding; Genecentrix: Consultancy; Tenebio: Other, Research Funding. Russell:Imanis: Other: Equity Ownership. OffLabel Disclosure: This describes of administration of Vesicular Stomatitis Virus Genetically Engineered to Express NIS and human interferon, in Patients with Relapsed or Refractory Hematologic malignacies