Citations

Abstract We conducted a two-stage Simon phase II, multi-center study in two groups: related and unrelated donor transplants. Based on the results of a previously conducted prospective study (MPD-RC 101, Rondelli et al, Blood, 2014) demonstrating relatively poor outcome in the unrelated donor arm due to high non-relapse mortality and graft failure (GF), we sought to improve this noted disparate outcome. The hypothesis driving this trial was that pre-transplant JAK1/2 inhibition would result in an increase in performance status, reduction in splenomegaly and inflammatory cytokine expression leading to improved HCT outcome. In the unrelated arm in the first 11 patients, the trial was to be terminated if 6 or more failures (GF or death due to any cause by 100 days post-transplant) were observed. In the related arm in the first 11 patients, the trial was to be terminated if 3 or more failures were observed. Key eligibility criteria included diagnosis of primary MF or post-PV MF or post-ET MF, age 18-70 years, and DIPSS int-2/high risk disease or int-1 risk disease with at least one additional risk factor. Patients could have received up to 6 months of ruxolitinib prior to enrollment provided that there was no evidence of loss of response to ruxolitinib during this period. Ruxolitinib was given for 56 days followed by a 4-day taper ending day -6. The conditioning regimen utilized was IV fludarabine 40 mg/m2 IV and IV busulfan 2.0 mg/KBW IV once daily for 4 days from days -5 to -2. GVHD prophylaxis consisted of cyclosporine or tacrolimus and methotrexate. Patients undergoing unrelated donor HCT also received low dose thymoglobulin (0.5 mg/KBW on day -3/2.0 mg/KBW on day -2 & day -1). The study has enrolled 21 patients (related, 7; unrelated, 14) with a median age of 59 years (range 39-70). 17 (81%) patients had palpable splenomegaly with median spleen size of 11 cm, and 16 patients had int-2/high risk disease. Of the 21 patients, 19 patients received transplantation (related 5/7 [71%], unrelated 14/14 [100%] underwent transplant). Two patients in the related arm did not proceed with transplantation as one progressed to acute myeloid leukemia (baseline blast count 14%) and another experienced sudden death of unknown cause the day after starting ruxolitinib. In addition, there was one GF in the related arm. Due to these 3 failures in the related arm, further enrollment was stopped in this arm per protocol criteria. In the unrelated arm, there were 4 failures (Table 1), and the study met the protocol criteria for further enrollment. Mean percent reduction from baseline to day -9 in palpable spleen length below the left costal margin was 30% (p=0.04) in 12 patients with palpable spleen. 5/12 (42%) had any reduction, and 4/12 (33%) had ≥50% reduction. From baseline to best score on day -9 or day -5, 11/19 (58%) patients with data had any improvement in MPN-SAF Total Symptom Score, and 7/19 (37%) had ≥50% reduction. Of the 19 patients undergoing transplant, ruxolitinib was tapered off successfully in all patients with no significant withdrawal syndrome or delay in transplant noted. In the pre-transplant phase, most common Grade 3 or higher toxicity considered to be related to ruxolitinib was anemia (6/21, 29%), and one patient had legionella pneumonia deemed not related to ruxolitinib. Median time to neutrophil recovery (> 0.5 x 109/L) and platelet recovery (>20 x 109/L) was 19 and 19.5 days. By day 100, 7/19 (37%) experienced Grade 2-4 acute GVHD (G2 in 5, G3 in 2). In the first 30 days post HCT, most common Grade 3 or higher toxicity was febrile neutropenia seen in 5/19 (26%) patients. In all 21 patients from time of registration with median follow-up of 5.8 months, 6-mo overall survival was 75% (95% CI 44-90%). For the 19 transplant recipients, 6-mo OS was 83% (95% CI 55-94%) from date of transplant. Conclusions: Stage 1 trial results highlight important observations. First, ruxolitinib may not be suitable for all myelofibrosis patients pre-transplant, eg, alternative approaches might be more appropriate in the context of accelerating disease. Second, we demonstrated a safe approach for tapering ruxolitinib prior to transplant which allowed patients to commence conditioning with reduced spleen size and symptoms. Third, pre-transplant ruxolitinib does not appear to have any adverse impact on early post-HCT outcomes following unrelated donor transplant, although Stage 2 enrollment will be required to better assess the potential benefits of this approach. Disclosures Gupta: Novartis: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Research Funding. Yacoub:Incyte: Consultancy, Honoraria, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Speakers Bureau; Alexion: Honoraria. Mesa:Promedior: Research Funding; Celgene: Research Funding; CTI: Research Funding; Gilead: Research Funding; Incyte: Research Funding; Galena: Consultancy; Ariad: Consultancy; Novartis: Consultancy. Mead:Novartis: Honoraria, Research Funding, Speakers Bureau. Mascarenhas:Novartis: Other: DSMB , Research Funding; Roche: Research Funding; Promedior: Research Funding; Janssen: Research Funding; CTI Biopharma: Research Funding; Incyte: Other: Clinical Trial Steereing Committee, Research Funding.

Abstract Several subsets of regulatory CD4+ T cells (CD4+ Tregs) have been described in peripheral blood and tumor microenvironment and blood of breast cancer (BC) patients and may play a key role in the progression of BC. High-risk human papilloma virus (HPV) have a causal role in a significant proportion of cervical, and head, and neck tumors and may play an important role in evoking neoplasia in BC. In this study we assessed the prevalence of CD4+Tregs (CD4+CD25+ FOXP3+ cells) and CD8+T cells by flow cytometry in peripheral blood from a total of 55 Egyptian women, including 20 treatment-naïve BC, 15 with breast benign lesions (BBL) and 20 healthy volunteers (HV). High-risk HPV genotype type 16, 18, and 31 was investigated in breast tissue from all BC and BBL patients using Real-Time PCR. HPV was detected in 4 BC, but in none of BBL patients. The frequency of CD4+ Tregs was significantly higher in BC compared to BBL and HV, (p < 0.001). In addition, we observed a significantly higher frequency of CD8+ T cells in peripheral blood of patients with late stage III compared to early stage I and II BC (p = 0.011). However, there was no significant association between the ratio of CD8+ T cell to CD4+ Tregs frequencies and the expression of Estrogen Receptor (ER), Progesterone Receptor (PR), and Human Epidermal Growth Factor Receptor 2 (HER2). In conclusion, CD4+ Tregs may contribute to progression BC in Egyptian women with HPV infection. The potential role CD4+ Tregs as a prognostic or predictive parameter should be analyzed in a larger longitudinal study with sufficient follow-up time.

BACKGROUND: Axi-cel is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy that is approved for treatment of relapsed/refractory (R/R) large B-cell lymphoma and is associated with high response rates and durable remissions. Recent data show that axi-cel is effective across various adverse prognostic features, namely cell of origin, disease bulkiness, and extranodal disease, among others. Hypoalbuminemia is a known adverse prognostic factor in lymphomas. It is unknown if axi-cel overcomes the adverse prognostic feature of hypoalbuminemia in R/R large B-cell or transformed follicular lymphoma. METHODS: We conducted a retrospective analysis of patients treated with axi-cel across three Mayo Clinic campuses (Rochester, Jacksonville, and Phoenix) from 06/01/2018 until 04/01/2019. The primary objective of this analysis was to assess the impact of hypoalbuminemia (defined at day 0, prior to infusion) on outcome after axi-cel therapy. RESULTS: A total of 50 (male=37, 74%) patients (pts), median age of 53 (26-67) years received axi-cel. The median number of prior lines of therapy was 3 (2-8) (Table 1). Two pts had no available serum albumin levels at time of axi-cel infusion. Seven (15%) of 48 pts had serum albumin levels lower than 3.5 g/dL (median= 3.3 g/dL (range 2.6-3.4)) and the median follow up of survivors was 7.6 (1.9-14.3) months. The best overall response rate (ORR) and complete remission (CR) rates in these pts were 57% and 57%, respectively. One (14%) patient had stable disease and 2 (29%) had disease progression. The median overall survival (OS) for pts with hypoalbuminemia was not reached. On the other hand, 41 (85%) pts had a normal serum albumin level (median=4.0 (range 3.5-5.1) g/dL) and the median follow up for survivors was 6.3 months. The best objective response rate (ORR) and complete remission (CR) rates in these pts were 82% and 44%, respectively. The median OS for pts with normal serum albumin was 14 (95%CI=6.3-29.6) months. There was no significant difference at 6-months and 1-year OS between pts with hypoalbuminemia vs. those with normal baseline serum albumin levels [6-month=100% vs. 79%(95%CI=64-93%); 1-year (100% vs. 54% (95%CI=26-82%), p=0.17] (Figure 1). All grades cytokine release syndrome (CRS) was diagnosed in all 7 pts with hypoalbuminemia (100%) and in 38 of 41 (92%) pts without hypoalbuminemia. There was no difference in the median duration of CRS between pts with or without hypoalbuminemia [6 (range 1-11) days vs 5 (range 1-19) days, p=0.89]. Neurotoxicity (all grades) was observed in 5 (71%) pts with hypoalbuminemia compared 26 (63%) with normal albumin levels. There was no statistically significant difference in median duration of neurotoxicity between pts with hypoalbuminemia and those with normal baseline albumin levels [9 (range 1-10) days vs. 3 (range 0-25) days, p= 0.72]. CONCLUSIONS: Hypoalbuminemia does not have a significant impact on the outcomes of axi-cel therapy, including the incidence of CRS or neurotoxicity. These results need to be validated in a large collaborative multicenter study. Further investigation is needed to assess the prognostic impact of severe hypoalbuminemia (<3g/dL) on axi-cel therapy. Disclosures Ansell: Mayo Clinic Rochester: Employment; Seattle Genetics: Research Funding; Trillium: Research Funding; Trillium: Research Funding; Mayo Clinic Rochester: Employment; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Affimed: Research Funding; Regeneron: Research Funding; Affimed: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; LAM Therapeutics: Research Funding; Affimed: Research Funding; Bristol-Myers Squibb: Research Funding; Trillium: Research Funding; Regeneron: Research Funding; Trillium: Research Funding; Affimed: Research Funding; LAM Therapeutics: Research Funding; Mayo Clinic Rochester: Employment; LAM Therapeutics: Research Funding; LAM Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; Mayo Clinic Rochester: Employment; Affimed: Research Funding; Regeneron: Research Funding; LAM Therapeutics: Research Funding; Seattle Genetics: Research Funding; Trillium: Research Funding; Affimed: Research Funding; Trillium: Research Funding; Bristol-Myers Squibb: Research Funding; LAM Therapeutics: Research Funding; Mayo Clinic Rochester: Employment; Trillium: Research Funding; Regeneron: Research Funding; LAM Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; LAM Therapeutics: Research Funding; Seattle Genetics: Research Funding; Trillium: Research Funding; Trillium: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; Bristol-Myers Squibb: Research Funding; Seattle Genetics: Research Funding; LAM Therapeutics: Research Funding; Regeneron: Research Funding; Affimed: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; Seattle Genetics: Research Funding; Affimed: Research Funding; Affimed: Research Funding. Bennani:Seattle Genetics: Other: Advisory board; Kite Pharma: Other: Advisory board; Seattle Genetics: Other: Advisory board; Adicet Bio: Other: Advisory board; Seattle Genetics: Other: Advisory board; Purdue Pharma: Other: Advisory board; Adicet Bio: Other: Advisory board; Purdue Pharma: Other: Advisory board; Purdue Pharma: Other: Advisory board; Adicet Bio: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Kite Pharma: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Kite Pharma: Other: Advisory board. Paludo:Verily Life Sciences: Research Funding; Celgene: Research Funding; Verily Life Sciences: Research Funding; Celgene: Research Funding. Tun:DTRM Biopharma: Research Funding; Mundi-pharma: Research Funding; BMS: Research Funding; Celgene: Research Funding; Curis: Research Funding; TG Therapeutics: Research Funding. Foran:Agios: Honoraria, Research Funding. Kharfan-Dabaja:Daiichi Sankyo: Consultancy; Pharmacyclics: Consultancy.

Background: Although diffuse large B cell lymphoma (DLBCL) can be cured using immuno-chemotherapy, 40% of patients experience relapse or refractory disease. Large-scale profiling studies have mainly focused on DLBCL at diagnosis, resolving different outcome groups based on gene expression (e.g. cell-of-origin (COO) or molecular high grade), MYC/BCL2 translocations (double-hit lymphoma) or gene mutations and copy number aberrations (Schmitz et al, NEJM 2018; Chapuy et al, NatureMedicine 2018). In comparison, longitudinal studies have been hindered by the limited availability of sequential biopsy samples. To date, the relapse-specific gene mutations identified are limited and inconsistent across studies. In our study, we have focussed attention on the changes in gene expression profile (GEP) accompanying DLBCL relapse. Methods: We retrospectively collected archival paired diagnostic/relapse formalin fixed paraffin embedded tumor biopsies from 38 de novo DLBCL patients collected from multiple UK sites treated with rituximab-based immuno-chemotherapy, where partial or complete remission was reported following treatment. COO classification was performed by the Lymph2Cx assay on NanoString to distinguish activated B-cell-like (ABC) and germinal center B-cell-like (GCB) subtypes. The Ion AmpliSeq™ Transcriptome Human Gene Expression Kit was used to measure the expression levels of > 20,000 genes on the paired samples. Results: COO remained stable from diagnosis to relapse in 17 ABC-ABC pairs, 11 GCB-GCB pairs and 4 unclassified (UNC)-UNC pairs. Frank COO switching was observed in 6 cases (1 ABC-GCB, 2 ABC-UNC, 2 GCB-UNC, 1 UNC-ABC). Pairs with stable COO were taken forward for further analysis. Gene expression analysis using the limma R package identified 163 and 136 genes as differentially expressed (DE) (p <= 0.01 and absolute log2FC > 1) between the diagnostic and relapse biopsies in ABC and GCB tumors respectively, with only a one gene overlap. Gene Set Enrichment Analysis further suggested that ABC and GCB relapses are mediated via different mechanisms, with tumor growth and proliferation signatures enriched in ABC relapses, whilst adaptive immunity-related signatures accompanied GCB relapses. Next, we aimed to utilise our relapse-specific genes to identify outcome predictors at diagnosis using publicly available GEP datasets. In order to increase our discovery power and accuracy, a larger set of DE genes from the paired differential analysis (796 genes in ABC pairs and 387 from GCB pairs) were selected (p <= 0.05) and subsequently used in a training cohort (GEP from Reddy et al, Cell 2017). The Prediction Analysis for Microarrays R (PAMR) algorithm identified a 30-gene signature within DE genes from ABC pairs (Fig1.A), capable of separating the 249 ABC cases into 136 low and 113 high-risk cases with significantly inferior overall survival (Hazard Ratio (HR)=1.89, log-rank p=0.0017, measure of goodness-of-fit C-index=0.71; Fig1.B). No equivalent signature was found in the GCB cases using this approach. The prognostic significance of this 30-gene discriminator was successfully validated using a linear predictor in two independent GEP datasets: 1) a population-based cohort (Lenz et al, NEJM 2008) with 93 R-CHOP-treated ABC cases identifying 47 low and 46 high-risk cases (HR=1.92, p=0.046, C-index=0.77; Fig1.C) and 2) a clinical trial dataset (REMoDL-B, Davies et al, Lancet Oncol 2019) with 255 ABC cases identifying 110 low and 145 high-risk ABC cases (HR=1.95, p=0.0051, C-index=0.70; Fig1.D). Conclusions: Here we describe a 30-gene discriminator in ABC-DLBCL, derived from genes differentially expressed between diagnosis and relapse, that allowed the definition of clinically distinct high and low risk subgroups in ABC-DLBCLs at diagnosis. The clinical translation of such a tool may be useful to guide therapy for this unfavourable subgroup of ABC-DLBCLs. Validation of this signature is currently underway in additional datasets and further study is required to understand the contribution of these genes in DLBCL pathology. Disclosures Korfi: Roche: Consultancy. Burton:Celgene: Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees. Rule:TG Therapeutics: Consultancy, Honoraria; Napp: Consultancy; Kite: Consultancy; Pharmacyclics: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Sunesis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Astra-Zeneca: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Crosbie:Janssen: Honoraria. Scott:Celgene: Consultancy; Janssen: Consultancy, Research Funding; NanoString: Patents & Royalties: Named inventor on a patent licensed to NanoSting [Institution], Research Funding; Roche/Genentech: Research Funding. Rimsza:NanoSting: Patents & Royalties: Named inventor on a patent licensed to NanoSting [Institution]. Davies:Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Research Funding; Bayer: Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Research Funding; Karyopharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Research Funding; Acerta Pharma: Honoraria, Research Funding; ADCT Therapeutics: Honoraria, Research Funding; BioInvent: Research Funding; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; MorphoSys AG: Honoraria, Membership on an entity's Board of Directors or advisory committees. Gribben:Abbvie: Consultancy, Honoraria, Research Funding; Acerta/Astra Zeneca: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Okosun:Gilead Sciences: Honoraria, Research Funding. Johnson:Epizyme: Honoraria, Research Funding; Novartis: Honoraria; Kite: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria; Boehringer Ingelheim: Honoraria; Takeda: Honoraria; Genmab: Honoraria; Celgene: Honoraria; Incyte: Honoraria. Fitzgibbon:Epizyme: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Speakers Bureau.

Introduction Novel high-risk groups have been identified in adult ALL, including secondary (sALL) and Philadelphia-like ALL (Ph-like, based on CRLF2, IgH, ABL2, JAK2 and other tyrosine kinase translocations), and those with minimal residual disease >0.1% (MRD+) after induction therapy. Novel targeted therapies are now routinely incorporated into 1st line regimens, including tyrosine kinase inhibitors (BCR-ABL1-pos), rituximab (CD20+) and blinatumomab (Blina) for MRD+. The impact of these novel high risk groups and therapies after alloHCT is unknown; therefore, we evaluated their impact on overall survival (OS), relapse rate (REL), non-relapse mortality (NRM) and acute and chronic GVHD. Methods We evaluated pts receiving 1st Allo-HCT for ALL at Mayo Clinic (Rochester, Phoenix, and Jacksonville) from 2008-2018 for outcomes of interest, specifically the impact of novel therapies and risk groups. Associations of patient factors with outcomes were examined using univariable (UVA) and multivariable (MVA) Cox proportional hazards regression models, where the cause-specific hazard of the given outcome was modeled to account for the competing risk of death. Results We identified 261 consecutive AlloHCT recipients during the study period. Median age at transplant was 48 years (18-72) and 147 (56.3%) were male. The median comorbidity (HCT-CI) score was 2 (0-8). 213 pts (81.6%) had B-lineage ALL, of which 85 (32.6%) were BCR-ABL-pos, 17 (6.5%) Ph-like (identified by FISH), 16 (6.1%) hypoploidy/near triploidy (Hy/Tri), and 67 (25.7%) pre-B ALL NOS. The remaining 48 (18.4%) had T-ALL. 30 pts (11.5%) had sALL (i.e. prior chemo/radiotherapy for another malignancy). HyperCVAD was the most common 1st line regimen (68.2%). 243 (93.1%) pts achieved Complete Remission (CR1) after induction therapy, and 203 (77.8%) were in CR1 at the time of alloHCT. Blina was administered for MRD+ in 14 pts (5.4%), and for relapsed/refractory ALL (R/R) in 13 (27% of R/R pts), 7 of whom received Blina as initial therapy for R/R. Donors were matched unrelated in 149 (57.1%), matched related in 98 (37.5%), and haploidentical in 14 (5.4%). Peripheral blood (PB) grafts were used in 233 (89.3%). 103 (54.5%) were donor:recipient (D:R) sex-matched, and 86 D:R mismatched [47 (24.9%) M:F; and 39 (20.6%) F:M]. Myeloablative conditioning was used for the majority (78.5%) mostly with Cy/TBI (60.5%). Standard GVHD prophylaxis regimens were used. Outcomes Median follow-up after transplant was 22.4 months (0.5-135), and 51 (19.5%) had REL. The 1, 2 and 5-year survival rates were 71.9%, 64.9%, and 54.1%, respectively (Figure 1). Acute GVHD developed in 144 (55.2%) and chronic GVHD in 100 (38.3%). Ph-like ALL, Blina for MRD+, Blina for R/R, sALL and CD20-pos had no independent impact on OS. In contrast, age>60, Hy/Tri, and >CR1 at alloHCT were associated with worse OS in UVA, however, in MVA only pre-B ALL NOS was associated with better OS. Female:male D:R status was associated with inferior OS. Blina for R/R disease was associated with increased risk of REL in UVA [HR 5.26 95% CI (1.33, 20.00), p=0.017], whereas other novel high risk groups had no impact on REL. In contrast, T-ALL, Hy/Tri and >CR1 at AlloHCT were associated with increased REL in UVA, but only T-ALL and Hy/Tri continued to predict for increased REL in MVA. Secondary ALL was associated with increased NRM in UVA [HR 1.96 95% CI (1.07, 3.57), p=0.028], whereas other novel high risk groups had no impact on NRM. In contrast, age>60, >CR1 at AlloHCT and D:R sex mismatch were associated with higher NRM in UVA, but only sex mismatch and >CR1 at AlloHCT were associated with higher NRM in MVA. TBI use was associated with higher risk of acute GvHD (p=0.008) and ATG use with lower risk chronic GVHD (p<0.001). Similarly non-PB grafts were associated with a lower risk of chronic GVHD (p=0.005). Results for OS, REL, NRM, acute and chronic GVHD analysis are shown in Table 1. Conclusion Novel high risk groups (CD20+, Ph-like and sALL) do not appear to adversely impact OS after alloHCT, although sALL was associated with increased risk of NRM. Interestingly, pre-B-ALL NOS appear to be associated with favorable OS. Novel targeted therapies also do not independently predict outcome, with the exception of Blina for R/R ALL which may be associated with REL after subsequent alloHCT (a subgroup for whom novel maintenance strategies should be explored). Our analysis highlights the importance of allo-HCT for novel high risk ALL subgroups. Disclosures Patnaik: Stem Line Pharmaceuticals.: Membership on an entity's Board of Directors or advisory committees. Kharfan-Dabaja:Daiichi Sankyo: Consultancy; Pharmacyclics: Consultancy. Foran:Agios: Honoraria, Research Funding.

(Text above this line is not copy/pasted in the abstract body) INTRODUCTION Allogeneic HCT using RIC regimens is the standard treatment for patients with relapsed/refractory cHL, however there is significant heterogeneity amongst the different regimens and a lack of data supporting a preferred RIC regimen. Using the CIBMTR database we evaluate the outcomes of the 3 most commonly used RIC regimens for cHL. METHODS In the CIBMTR registry, 492 adult patients underwent a first alloHCT using either a matched related or unrelated donor for cHL between 2008-2016, utilizing a RIC regimen with either fludarabine/ i.v. busulfan (6.4mg/kg) (Flu/Bu, n=102), fludarabine/melphalan 140mg/m^2 (Flu/Mel140, n=318) or fludarabine/cyclophosphamide (Flu/Cy, n=72). Graft-versus-host disease (GVHD) prophylaxis was calcineurin inhibitor (CNI) plus methotrexate, mycophenolate mofitil (MMF) or other agents, however post transplantation cyclophosphamide (post-CY) was excluded. The primary endpoint was overall survival (OS). Secondary endpoints included acute (a) and chronic (c) GVHD, non-relapse mortality (NRM), relapse/progression and progression-free survival (PFS). Probabilities of OS and PFS were calculated using the Kaplan-Meier estimator. Multivariable regression analysis was performed for GVHD, relapse/progression, NRM, PFS, and OS. Covariates with a p<0.01 were considered significant. RESULTS Baseline characteristics are shown in Table 1. The median patient age of the complete study cohort was only 33 years, with more than 80% receiving a prior autologous HCT. On multivariate analysis (Table 2), the 3 conditioning regimen cohorts were not statistically different in either risk of cGVHD nor risk of grade 3-4 aGVHD. No significant differences were seen in the NRM risk between the three regimens (p=0.54). Similarly, the risk of relapse (p=0.02) and PFS was comparable between regimens (p=0.14). Flu/Cy conditioning was associated with decreased risk of mortality in first 11months after alloHCT (OR 0.28, 95% CI 0.10-0.73, p=0.009, but beyond 11 months post alloHCT it was associated with a significantly higher risk of mortality, (OR 2.46, 95% CI 0.1.32-4.61, p=0.005; Figure 1) [11months post alloHCT cutoff chosen on the basis of the maximum likelihood value in the Cox model]. Four year adjusted PFS and OS were similar across the three regimens at 29% for Flu/Bu, 37% for Flu/Mel140 and 25% for Flu/Cy (p=0.07) for PFS and 62% for Flu/Bu, 59% for Flu/Mel140 and 55% for Flu/Cy (p=0.64) for OS, respectively. Relapse was the most common cause of death across all the regimens, followed by organ failure and GVHD. CONCLUSIONS The most commonly used RIC regimen in alloHCT for cHL is Flu/Mel140, which was compared to Flu/Bu and Flu/Cy, the next most frequently used regimens. The choice of conditioning regimen, in these young cHL patients (median age 33 years) did not confer any benefit in terms of the risk of relapse, decrease in NRM or improvement in PFS. There was no OS benefit between, Flu/Bu and Flu/Mel 140, but Flu/Cy was associated with a significantly higher risk of mortality in patients beyond 11 months from allo-HCT. Novel approaches are still needed to decrease post-HCT relapse risk and improve overall results. Figure 1 Disclosures Ghosh: Seattle Genetics: Consultancy, Speakers Bureau; Genentech: Research Funding; Gilead/Kite: Consultancy, Speakers Bureau; Pharmacyclics: Consultancy, Research Funding, Speakers Bureau; T G Therapeutics: Consultancy, Research Funding; Celgene: Consultancy, Research Funding, Speakers Bureau; Forty Seven Inc: Research Funding; Spectrum: Consultancy, Speakers Bureau; AbbVie: Consultancy, Speakers Bureau; Astra Zeneca: Speakers Bureau. Kharfan-Dabaja:Daiichi Sankyo: Consultancy; Pharmacyclics: Consultancy. Sureda:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; Gilead: Honoraria; Novartis: Honoraria; Amgen: Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria; Roche: Honoraria; Sanofi: Honoraria; Takeda: Consultancy, Honoraria, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Hamadani:Merck: Research Funding; Janssen: Consultancy; Otsuka: Research Funding; Takeda: Research Funding; Medimmune: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Research Funding; Celgene: Consultancy; Sanofi Genzyme: Research Funding, Speakers Bureau; Pharmacyclics: Consultancy.

Background: Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy approved for the treatment of adult patients who have relapsed/refractory large B cell lymphoma (LBCL) and have had ≥ 2 prior systemic therapies. In ZUMA-1, the registrational study of axi-cel in patients with refractory LBCL, the objective response rate was 83% (complete response rate, 58%), with ongoing responses in 39% after a median follow-up of 27.1 months (Locke FL, et al. Lancet Oncol. 2019). Despite the success of axi-cel, approximately 60% of patients have no response or relapse after treatment, indicating that additional strategies are needed for patients with relapsed/refractory LBCL. Preclinical murine studies have shown that rituximab augmented the tumor-suppressing effects of anti-CD19 CAR T cells, and the combination led to higher rates of tumor reduction (Mihara K, et al. Br J Haematol. 2010; Rufener GA, et al. Cancer Immunol Res. 2016). The IMiD® immunomodulatory agent lenalidomide has shown activity in patients with relapsed/refractory diffuse large B cell lymphoma and has also been shown to enhance the antitumor functions of anti-CD19 and anti-CD20 CAR T cells in mice (Otahal P, et al. Oncoimmunology. 2016). In ZUMA-14, the aim is to investigate the efficacy and safety of axi-cel in combination with rituximab or lenalidomide in adult patients with refractory LBCL. Methods: This Phase 2 study (NCT04002401) has a planned enrollment of approximately 60 patients aged ≥ 18 years with refractory LBCL, defined as a response of either progressive disease or stable disease to previous chemotherapy or progressive disease or relapse ≤ 12 months after an autologous stem cell transplant. Patients with prior IMiD® treatment, including lenalidomide, prior CAR T cell therapy, and/or prior CD19-targeted therapy are excluded. After leukapheresis, patients will be assigned 1:1 to receive axi-cel with either rituximab (Cohort 1) or lenalidomide (Cohort 2). Patients will receive lymphodepleting chemotherapy of fludarabine (30 mg/m2) and cyclophosphamide (500 mg/m2) on days -5 to -3 before axi-cel infusion (2 × 106 cells/kg) on Day 0. Cohort 1 will receive rituximab (375 mg/m2) every 28 days starting on Day -5 for a total of 6 doses. Cohort 2 will receive lenalidomide (10 mg) daily starting 7 days after leukapheresis through Day 3 and for 5 additional cycles (20 mg, first 21 days of each 28-day cycle) beginning after axi-cel infusion starting on Day 21. Patients may not receive any therapy other than conditioning therapy and rituximab or lenalidomide, as specified by cohort, between leukapheresis and axi-cel infusion. The primary endpoint is investigator-assessed complete response rate per the Lugano classification (Cheson BD, et al. J Clin Oncol. 2014). Key secondary endpoints include safety, objective response rate, duration of response, progression-free survival, overall survival, and pharmacokinetics (levels of blood CAR T cells over time). Exploratory endpoints for both cohorts include pharmacodynamic assessment of cytokine profiles and the rate of CD19-negative relapses. An additional exploratory endpoint for Cohort 2 is to investigate immunomodulation of the tumor microenvironment, including the number and activation of T cells and natural killer cells. Enrollment is expected to start in September 2019. Disclosures Neelapu: Cell Medica: Consultancy; Pfizer: Consultancy; BMS: Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Novartis: Consultancy; Precision Biosciences: Consultancy; Acerta: Research Funding; Karus: Research Funding; Incyte: Consultancy; Merck: Consultancy, Research Funding; Unum Therapeutics: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Cellectis: Research Funding; Allogene: Consultancy; Poseida: Research Funding. Kharfan-Dabaja:Daiichi Sankyo: Consultancy; Pharmacyclics: Consultancy. Oluwole:Pfizer: Consultancy; Spectrum: Consultancy; Gilead Sciences: Consultancy; Bayer: Consultancy. Krish:Celgene: Consultancy, Research Funding, Speakers Bureau; Genetech: Consultancy, Speakers Bureau; Pharmacyclics: Consultancy, Research Funding, Speakers Bureau; Takeda: Research Funding; Curis: Research Funding; MEI Pharma: Research Funding; Bristol Meyers Squibb: Research Funding; Xencor: Research Funding; Roche: Research Funding; AstraZeneca: Consultancy, Research Funding, Speakers Bureau; Sunesis: Consultancy, Research Funding. Reshef:BMS: Consultancy; Shire: Research Funding; Incyte: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding; Atara: Consultancy, Research Funding; Magenta: Consultancy; Pfizer: Consultancy; Pharmacyclics: Consultancy, Research Funding; Celgene: Research Funding. Riedell:Bayer: Honoraria, Speakers Bureau; Kite/Gilead: Honoraria, Research Funding, Speakers Bureau; Verastem: 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; Novartis: Research Funding. Stiff:Amgen: Research Funding; Gamida-Cell: Research Funding; Incyte: Research Funding; Cellectar: Research Funding; Unum: Research Funding; Gilead/Kite Pharma: Consultancy, Honoraria, Research Funding. Goyal:Kite, a Gilead Company: Employment. Kawashima:Kite, a Gilead Company: Employment, Equity Ownership. Milletti:Roche: Employment, Equity Ownership, Other: Travel Expenses, Patents & Royalties; Gilead: Employment, Equity Ownership, Other: Travel Expenses, Patents & Royalties; Kite, a Gilead Company: Employment. Oliva:Kite, a Gilead Company: Employment. Sun:Kite, A Gilead Company: Employment. Munoz:Pharmacyclics /Janssen: Consultancy, Research Funding, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Merck: Consultancy; Kyowa: Consultancy, Honoraria, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene/Juno: Consultancy, Research Funding; Genentech: Consultancy, Research Funding, Speakers Bureau; Kite/Gilead: Consultancy, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy; Alexion: Consultancy; Pfizer: Consultancy; Fosunkite: Speakers Bureau; AstraZeneca: Speakers Bureau; Portola: Research Funding; Incyte: Research Funding. OffLabel Disclosure: ZUMA-14 is a clinical trial evaluating the investigational combination of axicabtagene ciloleucel with either rituximab or lenalidomide in refractory large B cell lymphoma

Background: Sickle cell disease (SCD) is an inherited hemoglobinopathy which affects over 300,000 children born each year worldwide. In spite of improvement in supportive care in recent years, there is still a lack of effective treatment options. SCD leads to debilitating and cyclic episodes of erythrocyte sickling with progressive organ injury, contributing to lifetime morbidity and shortened life expectancy. Allogeneic HCT (allo-HCT) is a potentially curative therapy for SCD because engraftment is associated with resolution of the clinical phenotype of the disease and abrogation of its complications. Medical literature on allo-HCT for SCD is largely limited to children. Recent studies have evaluated the efficacy of allo-HCT in the adult population. Here, we conduct a systematic review/meta-analysis to assess the totality of evidence pertaining to the efficacy (or lack thereof) of allo-HCT in children and adults. Materials and methods: We performed a comprehensive search of the medical literature using PubMed/Medline, EMBASE and Cochrane library on July 3rd, 2019. We extracted data on clinical outcomes related to benefits (overall [OS] and disease free/event free survival [EFS/DFS]) and harms (non-relapse mortality [NRM] and graft failure [GF]), independently by two authors. Our search strategy identified 1001 references but only 30 studies (n= 1995 patients) were included in this systematic review/meta-analysis. We also performed a sub analysis on clinical outcomes for studies that included only pediatric patients (defined as <18 years) and those in patients ≥18 years of age. Results: Median age for patients enrolled in all the studies was at 10 years. Recurrent veno-occlusive crises represented the most common indication for allo-HCT followed by acute chest syndrome and stroke; nevertheless, most patients had more than one indication. Matched related donors (MRD) were the most common donor source (93%). Bone marrow was the most common source of hematopoietic stem cells (77%). Majority of patients underwent conditioning with myeloablative regimens (77%). Pooled OS rates (n=29 studies, 1681 patients) after allogeneic HCT was 95% (95%CI=93-96%) with low heterogeneity (I2=6.4%) among included studies (Figure 1). Pooled EFS/DFS rates (n=29 studies, 1894 patients) post-allografting was 90% (95%CI=87-93%) with moderate heterogeneity (I2=54%). Pooled NRM rates from 30 studies (1995 patients) was 4% (95%CI=2-6%) with low heterogeneity (I2=29.4%). Pooled GF rates from 28 studies (1851 patients) was 4% (95%CI=2-6%) with moderate heterogeneity (I2=55%). A subset analysis specifically for pediatric patients (n= 11 studies, 1009 patients, median age at 9.7 years) showed a pooled OS rate of 96% (95%CI=94-97%) with low heterogeneity (I2=0%); and for adult patients (n=3 studies, 51 patients, median age at 33.4 years) the pooled OS was 94% (95%CI=80-100%) with moderate heterogeneity (I2=52%). Pooled EFS/DFS for pediatric patients (n= 11 studies, 1009 patients) was at 89 %( 95%CI=84-93%) with moderate heterogeneity (I2=55.1%); and for adult patients (n=2 studies, 30 patients) was at 95% (95%CI=83-100%) with high heterogeneity (I2=96.5%). Pooled NRM from 10 studies with pediatric patients (281 patients) was at 6 % (95%CI=3-10%) with low heterogeneity (I2=0%); and from 3 studies with adult patients (51 patients) was at 1% (95%CI=0-7%) with low heterogeneity (I2=15.1%). Pooled GF from 10 studies with pediatric patients (281 patients) was at 3 % (95%CI=1-7%) with moderate heterogeneity (I2=40%); and from 2 studies with adult patients (30 patients) was at 5% (95%CI=0-17%) with high heterogeneity (I2=95.4%). Conclusions: The results of our systematic review/meta-analysis show excellent OS, EFS/DFS in children and adults undergoing allo-HCT with pooled OS rates exceeding 90%. The main limitation to offering an allo-HCT in SCD remains the availability of a suitable donor as 85% of patients meeting criteria do not have a MRD. We anticipate that with emergence of haploidentical transplantation the number of allo-HCT will increase in the future. GF remains a significant concern in this population and future studies should focus on novel immune suppression strategies to help reduce GF. Disclosures Kharfan-Dabaja: Pharmacyclics: Consultancy; Daiichi Sankyo: Consultancy.

Background Interferons are recognized as active agents in the treatment of patients with high risk essential thrombocythemia (ET) or polycythemia vera (PV), both in the upfront setting as well as beyond. Several trials have shown high rates of hematologic and molecular responses with the use of interferons, however, data on direct comparison of interferon activity in patients with early disease in comparison to patients refractory or resistant to prior therapies, such as hydroxyurea (HU) are lacking. We conducted a controlled analysis of the activity of pegylated interferon alfa-2a (PEG) in two prospective parallel clinical trials conducted in these two unique patient populations. Methods The MPD-RC 111 (NCT01259817) was an international, multicenter, phase 2 open-label clinical trial that evaluated PEG therapy in patients with high risk PV and high-risk ET who were either refractory or intolerant (R/I) to HU by modified ELN criteria. The MPD-RC 112 trial (NCT01258856) enrolled patients with high risk ET/PV who were treatment-naïve (TN) (HU <3 months) and randomized them (1:1) to PEG or HU. All patients randomized to PEG were included in this analysis. Both protocols were conducted concurrently at the MPD-RC member institutions and utilized a similar primary endpoint of overall response rate (complete and partial response rates) by ELN Criteria at 12 months confirmed by the same blinded central review committee. Both studies utilized the same PEG starting dose of 45 mcg weekly and was titrated for response to a maximum of 180 mcg weekly. Secondary endpoints included safety information, impact on disease biomarkers, bone marrow (BM) response, and quality of life data. Results Patients ET: 39 TN and 65 R/I ET patients were available for this analysis. Median disease duration was 2.9 months in TN and 37.3 months in R/I patients. Baseline characteristics and demographics were similar in the two cohorts except lower baseline hemoglobin level in RI patients. (Table1A) PV: 43 TN and 50 R/I PV patients were included. Median disease duration was 2.5 months in TN and 54.8 months in R/I patients. Baseline characteristics only differed by lower frequency of phlebotomy rate in R/I patients. (Table1B) Baseline symptoms scores and quality of life were similar in TN and RI groups (Table 2) Response ET: CR/PR/ORR at 12 months were observed in 43.1%/26.2%/69.2% in R/I ET patients and in 43.6%/25.6%/69.2% in TN ET patients (p=0.99 for ORR). (Table 3, Figure 1) PV: CR/PR/ORR at 12 months were observed in 22%/38%/60% in R/I PV patients, and in 27.9%/58.1%/86% in TN PV patients (p=0.005 for ORR). (Table 3, Figure 1) Safety PEG was equally well tolerated throughout both treatment groups with treatment discontinuation due to adverse events occurring in 14.6% in TN patients and 13.9% in R/I patients. The mean (SD) dose of PEG was 102.7 (52.3) mcg in R/I ET patients and 128.7mcg (46.4) in R/I PV patients. For TN patients, mean dose was 85.7mcg (59.7) in ET and 93.5 mcg (44.0) in PV. Adverse events were consistent with historic reports of PEG use and the distribution of events was similar in R/I and TN patients. (Table 4) Conclusion This intention to treat response analysis included TN and R/I ET and PV patients with balanced baseline characteristics who received prospective therapy with PEG. Patients with ET had a higher overall response rate at 12 months that was equivalent in patients who were treatment-naïve and in patients who were intolerant or refractory to HU. By contrast, patients with PV who were treatment-naïve had a higher ORR than patients those intolerant or refractory to HU. We conclude that treatment with PEG is an effective therapeutic option both treatment naïve PV and ET as well as those previously treated with HU, however PEG as a second line agent is especially effective in ET patients. Disclosures Yacoub: Hylapharm: Equity Ownership; Agios: Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Seattle Genetics: Honoraria, Speakers Bureau; Incyte: Consultancy, Honoraria, Speakers Bureau; Ardelyx: Equity Ownership; Cara: Equity Ownership; Dynavax: Equity Ownership. Mascarenhas:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Roche: Consultancy, Research Funding; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Pharmaessentia: Consultancy, Membership on an entity's Board of Directors or advisory committees; CTI Biopharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Research Funding; Promedior: Research Funding; Merus: Research Funding. Mesa:AbbVie: Research Funding; Samus: Research Funding; Incyte: Research Funding; Sierra Onc: Consultancy; Genotech: Research Funding; Promedior: Research Funding; Novartis: Consultancy; Celgene: Research Funding; CTI Biopharma: Research Funding; La Jolla Pharma: Consultancy. Rampal:Agios, Apexx, Blueprint Medicines, Celgene, Constellation, and Jazz: Consultancy; Constellation, Incyte, and Stemline Therapeutics: Research Funding. Silver:PharmEssentia: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. McMullin:Daiko Sanyo: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Speakers Bureau; Italopharma: Membership on an entity's Board of Directors or advisory committees. Ewing:Novartis: Honoraria, Other: Meeting attendance sponsorship ; Bristol Myers-Squibb: Other: Meeting attendance sponsorship . O'Connell:Astex: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Shionogi: Membership on an entity's Board of Directors or advisory committees. Mead:Bristol Myers-Squibb: Consultancy; Novartis: Consultancy, Honoraria, Other: Travel/accommodation expenses, Research Funding, Speakers Bureau; CTI: Honoraria, Research Funding; Celgene: Consultancy, Research Funding; Pfizer: Consultancy. De Stefano:Alexion: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau. Baer:Astellas: Research Funding; Al Therapeutics: Research Funding; Abbvie: Research Funding; Incyte: Research Funding; Forma: Research Funding; Kite: Research Funding; Takeda: Research Funding. Vannucchi:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Italfarmaco: Membership on an entity's Board of Directors or advisory committees; CTI BioPharma: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Kremyanskaya:La Jolla: Consultancy; Incyte, Celgene, Constellation, Protagonist.: Research Funding. Hexner:novartis: Research Funding. Rambaldi:Amgen: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Research Funding, Speakers Bureau; Italfarmaco: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Research Funding, Speakers Bureau; Omeros: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Research Funding, Speakers Bureau; Jazz: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau, travel support. Ritchie:Genentech: Other: Advisory board; Tolero: Other: Advisory board; agios: Other: Advisory board; Pfizer: Other: Advisory board, travel support; Celgene: Other: Advisory board; Jazz Pharmaceuticals: Research Funding; Celgene, Novartis: Other: travel support; AStella, Bristol-Myers Squibb, Novartis, NS Pharma, Pfizer: Research Funding; Ariad, Celgene, Incyte, Novartis: Speakers Bureau; Celgene, Incyte, Novartis, Pfizer: Consultancy. Kiladjian:Novartis: Honoraria, Research Funding; AOP Orphan: Honoraria, Research Funding; Celgene: Consultancy. Harrison:Promedior: Honoraria; Incyte: Speakers Bureau; Sierra Oncology: Honoraria; Celgene: Honoraria, Speakers Bureau; Janssen: Speakers Bureau; CTI: Speakers Bureau; AOP: Honoraria; Shire: Speakers Bureau; Roche: Honoraria; Gilead: Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau. Hoffman:Merus: Research Funding. OffLabel Disclosure: Pegylated Interferon Alfa-2a for in Patients with Polycythemia Vera or Essential Thrombocythemia

Background: Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of relapsed/refractory B-cell lymphoid malignancies. Axicabtagene ciloleucel (axi-cel), an anti-CD19 CAR-T not only targets the malignant B-cell, but can potentially also target and eliminate normal B-cells. This can interfere with the normal B-cell repertoire, compromising host humoral immunity such as decreased titers of common vaccines (DTaP, MMR). To assess if this was a clinically significant problem, we evaluated all recipients of axi-cel at our center between 6/2018 through 7/2019. Patients and methods: For patients who received commercial axi-cel, humoral immunity was evaluated both quantitatively [absolute lymphocyte count (ALC)] as well as qualitatively by serology titers [IgG antibodies (Abs)] for diphtheria, tetanus, pertussis, measles, mumps, and rubella, and total Immunoglobulin G (IgG) levels. Data was collected within 30 days prior to CAR-T infusion, then at day +30 and between days +60 and +100 after CAR-T infusion. Results: We identified 10 patients (males = 5, 50%), with a median age of 49.9 years (range 30-65) who received commercial axi-cel during the study period. Patient characteristics and indications for CAR-T therapy are shown in Table 1; the cohort represented a heavily pre-treated aggressive B-cell lymphoma patient population. Baseline information on antibody (Ab) titers was available in 8 patients. At baseline, all patients had positive tetanus IgG Abs (≥0.01 IU/mL), 7 had positive diphtheria IgG Abs (≥0.01 IU/mL), 6 had positive measles IgG Abs (≥ 1.1 AI), 5 had positive rubella IgG Abs (≥ 1.0 AI), 3 had positive mumps IgG Abs (≥ 1.1 AI). None of the patients had a positive pertussis IgG Abs (≥100 IU/mL). At follow-up, all patients with positive Ab at baseline maintained titers in the positive range at day +30 and between days +60 and +100 (Figure 1). None of the patients demonstrated a clinically meaningful decrease in Abs titers, despite a drop in ALC and IgG levels (table 2). Conclusions: Albeit a small sample size, IgG Ab titers for diphtheria, tetanus, measles, mumps, and rubella did not appear to be affected by axi-cel at a short interval follow-up after infusion (up to day +100). We plan to extend this analysis in a larger cohort with a longer-term prospective follow-up to validate our findings, especially in light of dropping absolute lymphocyte counts and IgG levels. Disclosures Ailawadhi: Celgene: Consultancy; Amgen: Consultancy, Research Funding; Cellectar: Research Funding; Janssen: Consultancy, Research Funding; Takeda: Consultancy; Pharmacyclics: Research Funding. Foran:Agios: Honoraria, Research Funding. Tun:Celgene: Research Funding; Curis: Research Funding; TG Therapeutics: Research Funding; Mundi-pharma: Research Funding; DTRM Biopharma: Research Funding; BMS: Research Funding. Chanan-Khan:Pharmacyclics: Research Funding; Merck: Research Funding; Jansen: Research Funding; Mayo Clinic: Employment; Ascentage: Research Funding; Millennium: Research Funding; AbbVie: Research Funding; Xencor: Research Funding. Kharfan-Dabaja:Daiichi Sankyo: Consultancy; Pharmacyclics: Consultancy.