Abstract: Race has a differential impact on the survival of patients with translocation t(11;14) multiple myeloma who undergo autologous hematopoietic cell transplantation. African Americans with t(11;14) have superior survival in comparison with Whites after adjustments for other prognostic factors.

Abstract: Autologous hematopoietic stem cell transplantation in patients with primary and relapsed/refractory multiple myeloma induces a response in a significant proportion of patients, even in those who are refractory to proteasome inhibitors and immunomodulatory agents.

Abstract: The optimal duration of lenalidomide (Len) maintenance for patients with multiple myeloma (MM) after autologous stem cell transplantation (autoHCT) is unknown. We conducted a retrospective single‐center analysis of adult MM patients that received upfront autoHCT between 2005 and 2021, followed by single‐agent Len maintenance. A total of 1167 patients were included with a median age of 61.4 (range 25.4–82.3) years, and high‐risk chromosomal abnormalities in 19%. Median duration of maintenance was 22.3 (range 0.03–139.6) months. After a median follow‐up of 47.9 (range 2.9–171.7) months, median PFS and OS for the entire cohort were 56.6 (95% CI 48.2–61.4) months and 111.3 (95% CI 101.7–121.5) months, respectively. In MVA, high‐risk cytogenetics was associated with a worse PFS (HR 1.91) and OS (HR 1.73) ( p   〈  .001 for both). Use of KRD induction and achievement of MRD‐negative ≥ VGPR before autoHCT were associated with an improved PFS (HR 0.53 and HR 0.57, respectively; p   〈  .001 for both). Longer maintenance duration, even with a 5‐year cutoff, was associated with superior PFS and OS (HR 0.17 and 0.12, respectively; p   〈  .001 for both). A total of 106 patients (9%) developed a second primary malignancy (SPM), mostly solid tumors (39%) and myeloid malignancies (30%). Longer maintenance duration was associated with a higher risk of SPM, reaching statistical significance after 〉 2 years (odds ratio 2.25; p   〈  .001). In conclusion, outcomes with Len maintenance were comparable to those reported in large clinical trials. Longer duration of maintenance, even beyond 5 years, was associated with improved survival.

Abstract: Epilepsy is one of the most common and devastating neurological disorders that causes unprovoked, recurrent seizures arising from excessive synchronized neuronal discharging. Although antiepileptic drugs (AEDs) reduce the frequency of epilepsy seizures, drug-refractory epileptic patients exert resistance to AEDs, resulting in treatment difficulty. Moreover, pharmacological treatments do not show satisfactory results in response to photosensitive epilepsy. In the recent era, light therapy emerged as a potential non-pharmacological approach for treating various diseases, including depression, seasonal affective disorders, migraine, pain, and others. Several studies have also shown the potential of light therapy in treating epilepsy. In addition, Red light evokes epilepsy seizures. Blue lenses filter the red light and significantly suppress the frequency of epilepsy seizures. However, the effects of green light on the frequency of epileptic seizures are not studied yet. In addition, light-activated gene therapy or optogenetics also emerged as a possible option for epilepsy treatment. Animal models have shown the therapeutic possibilities of optogenetics and light therapy; however, human studies addressing this possibility are still vague. This review provides the beneficial effects of light in reducing seizure frequency in epilepsy patients. A limited number of studies have been reported so far; therefore, light therapy for treating epilepsy requires more studies on animal models to provide precise results of light effects on seizures.

Abstract: Background: Graft-versus-host disease (GVHD) is a major complication of allogeneic stem cell transplantation (ASCT). The incidence of GVHD with conventional GVHD prevention is higher with HLA mismatched compared to matched donors, with 69% of patients (pts) developing grade 2-4 and 16% grade 3-4 acute (aGVHD) and more than half the pts developing chronic (cGVHD), as previously reported by us(Ciurea SO abstract ASH 2010). Here we report preliminary results of 9/10 MUD transplant pts receiving GVHD prophylaxis with post-transplantation cyclophosphamide (PTCY), in addition to tacrolimus and mycophanolate mofetil (MMF). Methods: Patients were treated prospectively using a 9/10 MUD on a separate arm of a phase II clinical trial (2009-0266). Conditioning regimen consisted of Melphalan 140 mg/m2 on day −8 (100mg/m2 for pts ≥55 years or with comorbidities), Thiotepa 5-10 mg/kg on day −7 and Fludarabine 40 mg/m2/day on days −6, −5, −4, and −3. All patients received T-cell replete bone marrow graft. GVHD prophylaxis included PTCY 50mg/kg on days +3 and +4, MMF was given until day 100 and Tacrolimus until day 180 if no GVHD. Primary objectives were to determine the incidence of acute and chronic GVHD and non-relapse mortality (NRM), while secondary objectives included progression free survival (PFS) and overall survival (OS). Results: 39 patients with median age of 50 years (range 20-64) received a 9/10 MUD with PTCY GVHD prophylaxis. 20 patients (51%) were women and AML/MDS was the most common indication for transplantation in 13(33%), NHL 8(21%), ALL 7(18%), AA in 4(10%) and CLL, CML/MPD, HL and MM constituted rest of the patients. Poor, intermediate and low risk cytogenetics were seen in 6, 8 and 4 patients with leukemia, respectively. 22 patients (56%) were not in complete remission at the time of transplantation. Median follow-up time for survivors was 35.9 months (range: 2.6–123.5). All patients engrafted the donor cells. Day 100 NRM for all pts was 18%.The cumulative incidence (CI) of grade II-IV aGVHD and gr III-IV aGVHD was 42% and 17%, respectively. CI of all cGVHD was only 20% and extensive only cGVHD was 13%. NRM for all pts was 36% at 1 year and 40% at 3 years. OS for all pts at 1 and 3 yr was 57% and 44%, while PFS at 1 and 3 yr was 43% and 39%, respectively. Conclusions: Post-transplant cyclophosphamide for prevention of GVHD which has been successfully used in haploidentical transplantation, resulted in a modest improvement in the rates of grade 2-3 and 3-4 acute GVHD compared to reports of standard GVHD prophylaxis for 9/10 MUD transplants. However, a promising low rate of chronic GVHD was observed. This approach can produce durable remissions for patients with hematologic malignancies who lack an HLA matched donor. Figure 1 Figure 1. Disclosures Andersson: Otsuka Pharmeceuticals: Research Funding, Research funding from Otsuka Pharmeceuticals Other.

Abstract: Background: Inotuzumab Ozogamicin (INO) is a humanized anti-CD22 monoclonal antibody that has emerged as an attractive therapeutic target for CD22+ b-cell lymphoid malignancies. We prospectively studied the safety and efficacy of INO when added to our standard nonmyeloablative allogeneic stem cell transplant (alloSCT) conditioning regimen of BFR (bendamustine, fludarabine and rituximab) (Khouri IF, et al. Blood 2014;124:2306). We also compared results to patients who received BFR+alloSCT without INO in prior trial. Methods: INO was infused intravenously (IV) on day -13 outpatient, with a dose cohort of 0.6, 1.2 or 1.8 mg/m2, to determine the maximum tolerated dose. Bendamustine 130 mg/m2 IV daily on days -5 to -3 together with 30 mg/m2 IV of fludarabine on days -5 to -3 were given prior to transplantation. Rituximab was given at a dose of 375 mg/m2 IV on days -6, +1, and +8. Tacrolimus and mini-methotrexate were used for graft versus host disease (GVHD) prophylaxis. In addition, thymoglobulin 1 mg/kg IV was given on days -2, and -1 in patients receiving a matched unrelated donor (MUD) transplant. Results: AlloSCT with INO.The study group included 26 patients treated between December 2012 and September 2019. Median age was 59 (range, 26-70) years. Eleven (42% had an HCT-CI & gt;3. Disease types: CLL [n=7 (27%) ; 2 with TP53 mutations, 2 others with 17p-; 4 with unmutated immunoglobulin heavy chain gene], Richter's (n=4, 15%), mantle cell lymphoma (MCL) [n=8 (31%); 6/6 patients tested had Ki 67 & gt;30%; 1 had blastoid histology and 1 had 17p-], follicular lymphoma (n=5, 19%), and diffuse large b cell (DLBCL[n= 2 (8%); including 1 double-expressor subtype] . Median prior treatments was 2.5 (range, 1-6). CLL patients were previously treated with ibrutinib (n=6, 86%; 5 had the drug discontinued due to refractoriness to ibrutinib, one had poor tolerance, and 1 was bridged to transplant), idelalisib (n=2, refractory), venetoclax (n=4; sensitive), CAR-T cell (n=1, refractory). One patient with Richter refractory to nivolumab+chemotherapy. Four MCL patients were previously treated with ibrutinib (2 had progression, 2 were bridged to transplant). At study entry, 18 (69%) patients were in CR, 7 (27%) in PR, and 1 (4%) had SD. Eleven (42%) received their transplants from HLA-compatible siblings and 15 (58%) from MUDs. The number of patients who received the 0.6, 1.2 or 1.8 mg/m2 of INO were 4, 2 and 20 patients, respectively. No DLT was observed. Neutrophil counts recovered to & gt; 0.5 x 109/L a median of 6 days after transplantation (range, 0-12). Eleven patients (42%) never experienced an ANC & lt; 0.5 x 109/L and 20 (77%) never experienced a platelet counts & lt; 20K x 109/L. All patients engrafted donor cells and no secondary graft failure occurred. By day 30, median donor myeloid and T-cells were 92% and 99%, respectively. Both increased to 100% by day 90. The CI acute grade 2-4 GVHD, 3-4 GVHD and 1-year chronic extensive GVHD were 27%, 4 % (none had grade 4) and 31%, respectively. Non-relapse mortality (NRM) at 5-years was 11.7%. With a median follow-up time of 49 (range, 4-83) months, the 5-year OS and PFS rates were 84% and 81%, respectively (Figure 1). Control group: AlloSCT without INO. We compared results to a group of patients (n=56) with relapsed lymphoid malignancies who received alloSCT at our center on a preceding prospective trial between April 2009 and February 2013, using BFR conditioning without INO and the same GVHD prophylaxis. There was no statistically significant difference in patients, disease or transplant characteristics between the 2 groups. We also found no statistically significant differences in engraftment times, % donor cell, 5-year NRM (12.5%), risk of acute 2-4 or 3-4 GVHD. Liver toxicity encountered between the two groups is summarized in Table 1. The 5-year OS and PFS was 75% and 62%, respectively (Figure 2). Conclusions: Our results show that INO at a dose level of 1.8 mg/m2 is well-tolerated when combined with the BFR nonmyeloablative allogeneic conditioning regimen for lymphoid malignancies. No added toxicity or increased myelosuppression were observed compared to patients who received BFR alone. An ongoing trial at our center includes patients with acute lymphoblastic leukemia evaluating INO added during conditioning and post- alloSCT for maintenance. Disclosures Khouri: Bristol Myers Squibb: Research Funding; Pfizer: Research Funding. Jain:Fate Therapeutics: Research Funding; BeiGene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Aprea Therapeutics: Research Funding; Verastem: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cellectis: Research Funding; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; ADC Therapeutics: Research Funding; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Research Funding; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Precision Bioscienes: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Kadia:Abbvie: Honoraria, Research Funding; Cellenkos: Research Funding; Pulmotec: Research Funding; Amgen: Research Funding; Cyclacel: Research Funding; Incyte: Research Funding; BMS: Honoraria, Research Funding; Celgene: Research Funding; Astellas: Research Funding; Ascentage: Research Funding; Pfizer: Honoraria, Research Funding; Astra Zeneca: Research Funding; Novartis: Honoraria; JAZZ: Honoraria, Research Funding; Genentech: Honoraria, Research Funding. Pemmaraju:Roche Diagnostics: Honoraria; Samus Therapeutics: Research Funding; Blueprint Medicines: Honoraria; Celgene: Honoraria; SagerStrong Foundation: Other: Grant Support; LFB Biotechnologies: Honoraria; Novartis: Honoraria, Research Funding; DAVA Oncology: Honoraria; Affymetrix: Other: Grant Support, Research Funding; MustangBio: Honoraria; Daiichi Sankyo: Research Funding; Plexxikon: Research Funding; Incyte Corporation: Honoraria; Cellectis: Research Funding; Stemline Therapeutics: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; Pacylex Pharmaceuticals: Consultancy. Bashir:Celgene: Research Funding; StemLine: Research Funding; Acrotech: Research Funding; Takeda: Other: Advisory Board, Research Funding; Purdue: Other: Advisory Board; Amgen: Other: Advisory Board; KITE: Other: Advisory Board. Kebriaei:Novartis: Other: Served on advisory board; Kite: Other: Served on advisory board; Ziopharm: Other: Research Support; Pfizer: Other: Served on advisory board; Jazz: Consultancy; Amgen: Other: Research Support. Popat:Bayer: Research Funding; Novartis: Research Funding. Nastoupil:Genentech, Inc.: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Karus Therapeutics: Research Funding; Gamida Cell: Honoraria; Bayer: Honoraria; Gilead/KITE: Honoraria; Novartis: Honoraria, Research Funding; Merck: Research Funding; Janssen: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; TG Therapeutics: Honoraria, Research Funding; LAM Therapeutics: Research Funding. Flowers:BeiGene: Consultancy; Burroughs Wellcome Fund: Research Funding; TG Therapeutics: Research Funding; Bayer: Consultancy; Denovo Biopharma: Consultancy; AbbVie: Consultancy, Research Funding; Acerta: Research Funding; Leukemia and Lymphoma Society: Membership on an entity's Board of Directors or advisory committees; V Foundation: Research Funding; Kite: Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; OptumRx: Consultancy; Eastern Cooperative Oncology Group: Research Funding; Cancer Prevention and Research Institute of Texas: Research Funding; National Cancer Institute: Research Funding; Spectrum: Consultancy; Pharmacyclics/Janssen: Consultancy; Karyopharm: Consultancy; Millennium/Takeda: Consultancy, Research Funding; Celgene: Consultancy, Research Funding. Kantarjian:Novartis: Research Funding; Jazz Pharma: Research Funding; Agios: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Cyclacel: Research Funding; Actinium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Daiichi-Sankyo: Research Funding; Immunogen: Research Funding; Astex: Research Funding; Takeda: Honoraria; AbbVie: Honoraria, Research Funding; BMS: Research Funding; Ariad: Research Funding. Champlin:Actinium: Consultancy; Takeda: Patents & Royalties; Genzyme: Speakers Bureau; DKMS America: Membership on an entity's Board of Directors or advisory committees; Johnson and Johnson: Consultancy; Omeros: Consultancy; Cytonus: Consultancy. Jabbour:Pfizer: Other: Advisory role, Research Funding; BMS: Other: Advisory role, Research Funding; Genentech: Other: Advisory role, Research Funding; Takeda: Other: Advisory role, Research Funding; Adaptive Biotechnologies: Other: Advisory role, Research Funding; AbbVie: Other: Advisory role, Research Funding; Amgen: Other: Advisory role, Research Funding. OffLabel Disclosure: Use Of Inotuzumab Ozogamicin in conditioning for allogeneic transplantation

Abstract: Background: Cardiac involvement by light chain amyloidosis (AL) is generally associated with an unfavorable outcome. Bortezomib-based induction, and high-dose melphalan followed by autologous hematopoietic stem cell transplantation (auto-HCT) in eligible patients is associated with best long-term outcomes. We report the outcome of cardiac AL patients who underwent auto-HCT at our institution. Methods: We retrospectively reviewed all patients with cardiac AL who received auto-HCT between January 1997 and December 2018 at our institution. Hematologic and cardiac organ responses were evaluated according to the Consensus Guidelines for AL (R Comenzo et al. Leukemia 2012). Revised Mayo staging system was used for cardiac staging (S Kumar et al. JCO 2012). Progression free survival (PFS) and overall survival (OS) were calculated from the date of transplant. Survival was estimated using Kaplan Meier method and compared using log rank test. Cox proportional hazard models were used for adjusted survival analysis. Results: 57 patients were identified and baseline characteristics summarized in Table 1. Thirty eight patients (67%) at diagnosis and 17 (30%) at auto-HCT were evaluable by the revised Mayo staging system. Eleven (19%), 14 (25%), 17 (30%), and 13 (23%) patients had stage 1, 2, 3 and 4 disease, respectively, while the stage was unknown in 2 (3%) patients. Twenty-four (42%) patients received induction with a combination of cyclophosphamide, bortezomib, and dexamethasone (CyBorD), 14 (25%) received bortezomib and dexamethasone, and 2 (3%) received other bortezomib-based induction (Table 1). Based on hematologic response criteria, 3 (5%), 15 (27%) and 22 (39%) patients achieved complete response (CR), a very good partial response (VGPR), or partial response (PR) to induction, with an overall response rate (ORR) of 71%. All patients underwent peripheral blood stem cell (PBSC) mobilization with filgrastim, with or without plerixafor. Thirty-nine (68%) patients received melphalan 200mg/m2 and 18 (32%) received melphalan 140mg/m2 as preparative regimen. Nineteen patients (33%) received maintenance therapy post auto-HCT. One-hundred day and 1-year post auto-HCT non-relapse mortality rate was 5% (3 patients). Best post auto-HCT hematologic ORR was 92%, with 19 (34%), 20 (35%), and 13 (23%) patients achieving CR, VGPR and PR, respectively. Based on the consensus guidelines for cardiac response in AL using NT-proBNP or NYHA class, 51 patients (89%) had a cardiac organ response at their last evaluation (Table 2). Median follow up in surviving patients was 32.9 months (range 5.1 - 140.6). The 3-year PFS was 53.5% [95% CI 38.6-68.4%], and 3-year OS was 67.8% [53.9-81.7%] . On univariate analysis, melphalan 200 vs. 140 (p=0.017, HR 0.387 95%CI 0.178- 0.844) was associated with a better PFS, but none of the variables had an impact on PFS or OS on a multivariate Cox regression analysis, perhaps due to a small sample size. Conclusion: In this retrospective analysis we showed that in transplant-eligible patients with advanced cardiac AL, high-dose melphalan and auto-HCT is associated with a low (5%) NRM, an organ response rate of almost 90%, and a 3-year OS of almost 70%. Disclosures Bashir: Takeda: Other: Advisory Board, Research Funding; Acrotech: Research Funding; Celgene: Research Funding; StemLine: Research Funding; KITE: Other: Advisory Board; Purdue: Other: Advisory Board; Amgen: Other: Advisory Board. Nieto:Secura Bio: Other: Grant Support; Astra Zeneca: Other: Grant Support; Novartis: Other: Grant Support; Affimed: Consultancy, Other: Grant Support. Hosing:NKARTA Inc.: Consultancy. Popat:Bayer: Research Funding; Novartis: Research Funding. Lee:Takeda: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; GlaxoSmithKline: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Genentech: Consultancy; Genentech: Consultancy; Daiichi Sankyo: Research Funding; Sanofi: Consultancy; Regeneron: Research Funding. Patel:Takeda: Consultancy, Research Funding; Precision Biosciences: Research Funding; Oncopeptides: Consultancy; Poseida: Research Funding; Janssen: Consultancy, Research Funding; Nektar: Consultancy, Research Funding; Cellectis: Research Funding; Celgene: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding. Manasanch:Merck: Research Funding; Sanofi: Honoraria; GSK: Honoraria; Takeda: Honoraria; Quest Diagnostics: Research Funding; Adaptive Biotechnologies: Honoraria; JW Pharma: Research Funding; Novartis: Research Funding; BMS: Honoraria; Sanofi: Research Funding. Thomas:X4 Pharma: Research Funding; Ascentage: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; Genentech: Research Funding; Xencor: Research Funding; Pharmacyclics: Other: Advisory Boards. Kaufman:Karyopharm: Honoraria; Janssen: Research Funding; Bristol Myers Squibb: Research Funding. Orlowski:Sanofi-Aventis, Servier, Takeda Pharmaceuticals North America, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Laboratory research funding from BioTheryX, and clinical research funding from CARsgen Therapeutics, Celgene, Exelixis, Janssen Biotech, Sanofi-Aventis, Takeda Pharmaceuticals North America, Inc.: Research Funding; Amgen, Inc., AstraZeneca, BMS, Celgene, EcoR1 Capital LLC, Forma Therapeutics, Genzyme, GSK Biologicals, Ionis Pharmaceuticals, Inc., Janssen Biotech, Juno Therapeutics, Kite Pharma, Legend Biotech USA, Molecular Partners, Regeneron Pharmaceuticals, Inc.,: Honoraria, Membership on an entity's Board of Directors or advisory committees; STATinMED Research: Consultancy; Founder of Asylia Therapeutics, Inc., with associated patents and an equity interest, though this technology does not bear on the current submission.: Current equity holder in private company, Patents & Royalties. Champlin:Takeda: Patents & Royalties; Genzyme: Speakers Bureau; DKMS America: Membership on an entity's Board of Directors or advisory committees; Cytonus: Consultancy; Omeros: Consultancy; Johnson and Johnson: Consultancy; Actinium: Consultancy. Qazilbash:Bioclinica: Consultancy; Amgen: Research Funding; Angiocrine: Research Funding; Bioline: Research Funding; Janssen: Research Funding.