Incidence of Oxaliplatin Hypersensitivity Reaction Among Colorectal Cancer Patients: a 5-Year Retrospective Study

PurposeWe explored the clinical data of colorectal cancer patients treated with oxaliplatin-based regimen to determine the incidence, severity, and risk factors of oxaliplatin-related hypersensitivity reaction (HSR). MethodThis retrospective study investigated 245 colorectal cancer patients (1,690 treatment cycles) receiving care at King Chulalongkorn Memorial Hospital, Thai Red Cross society between January 1, 2015, and December 31, 2019. The patients’ demographic data, laboratory data, and clinical features suggesting hypersensitivity reactions to oxaliplatin were reviewed. The Fisher’s Exact test and unpaired t-test were used to determine the differences among patients with and without oxaliplatin HSR. The potential risk factors for oxaliplatin HSR were analyzed for statistical significance by logistic regression.Results A total of 245 colorectal cancer patients (1,690 treatment cycles) were included in this study. The incidence of oxaliplatin HSR was 37.96%, according to the NCI-CTCAE v.5, (grade 1, grade 2, and higher grades were 27.35% (67 patients), 6.53% (16 patients), and 4.08% (10 patients), respectively). The proportion of male patients and patients with history of prior exposure to platinum-based chemotherapy were statistically higher in the HSR group. The eosinophil count and serum creatinine level were also significantly greater in the HSR group. On the contrary, the total lymphocyte count and serum albumin level were significantly lower in the HSR group. The multivariate logistic regression found 5 risk factors with significant difference. Male gender, prior exposure to platinum-based chemotherapy, and elevated eosinophil count were associated with increased risk of oxaliplatin HSR, whereas elevated monocyte count and elevated serum albumin were protective factors for the development of oxaliplatin HSR. ConclusionColorectal cancer patients treated with oxaliplatin-based regimen with male gender, prior exposure to platinum-based chemotherapy, and elevated eosinophil count have a greater risk of oxaliplatin related hypersensitivity reactions.

Living in a Fluctuating Environment Increases Tolerance to Marine Heatwaves in the Free-Living Coralline Alga Phymatolithon lusitanicum

Recently, increased attention is being paid to the importance of environmental history in species’ responses to climate-change related stressors, as more variable and heterogeneous environments are expected to select for higher levels of plasticity in species tolerance traits, compared to stable conditions. For example, organisms inhabiting environments with highly fluctuating thermal regimes might be less susceptible to the increasing frequency and intensity of marine heatwaves (MHWs). In this study, we assessed the metabolic and calcification responses of the rhodolith-bed forming Phymatolithon lusitanicum, from a coastal region that is strongly influenced by frequent changes between upwelling and downwelling conditions, to a simulated MHW scenario, with and without prior exposure to a moderate thermal stress. This allowed determining not only the influence of the species’ long-term thermal history on its resilience against MHWs, but also the rhodoliths capacity for short-term thermal stress memory and its importance during posterior MHW-exposure. Our findings indicate that the rhodoliths experienced negative impacts on daily net primary production (DNP) and calcification (DNC) during the MHW. The effect on the former was only temporary at the beginning of the MHW, while DNC was highly impacted, but exhibited a quick recovery after the event, suggesting a high resilience of the species. Furthermore, prior exposure to a moderate temperature increase, such as those occurring frequently in the natural habitat of the species, mitigated the effects of a subsequent MHW on DNP, while promoting a faster recovery of DNC after the event. Thus, our findings (1) support the hypothesis that benthic organisms living in nearshore habitats may benefit from the natural short-term temperature fluctuations in these environments with an increased resistance to MHW impacts and (2) provide first-time evidence for thermally induced stress memory in coralline algae.

Prior exposure to microcystin alters host gut resistome and is associated with dysregulated immune homeostasis in translatable mouse models

The increased propensity of harmful algal blooms (HABs) and exposure from HABs-cyanotoxin causes human toxicity. It has been associated with the progression of several diseases that encompass the liver, kidneys, and immune system. Recently, a strong association of cyano-HAB toxicity with the altered host gut microbiome has been shown. We tested the hypothesis that prior exposure to cyanotoxin microcystin may alter the microbiome and induce microbiome-host-resistome crosstalk. Using both wild-type and humanized mice, we show that the mice exposed to microcystin had an altered microbiome signature that harbored antimicrobial resistance genes. Host resistome phenotypes such as mefA, msrD, mel, ant6, and tet40 increased in diversity and relative abundance following microcystin exposure. Interestingly, the increased abundance of these genes was traced to resistance to common antibiotics such as tetracycline, macrolides, glycopeptide, and aminoglycosides, crucial for modern-day treatment for several diseases. Increased abundance of these genes was positively associated with increased expression of PD1, a T-cell homeostasis marker, and pleiotropic inflammatory cytokine IL-6 with a concomitant negative association with immunosurveillance markers IL7 and TLR2. Microcystin exposure also caused decreased TLR2, TLR4, and REG3G expressions, increased immunosenescence, and higher systemic levels of IL-6 in both wild-type and humanized mice. In conclusion, the results show a first-ever characterization of the host resistome of microcystin exposure and its connection to host immune status and antibiotic resistance. The results may be crucial for understanding the ability of exposed subjects to fight future bacterial infections and the progression of the debilitating disease in hospital settings.

Effects of PARP Inhibitor Therapy on p53-Deficient Hematopoietic Stem and Progenitor Cell Fitness

Poly (ADP-ribose) polymerase (PARP) inhibitors are an important new class of anti-cancer therapies. Therapy-related myeloid neoplasia (tMN) has been reported following PARPi therapy and is associated with adverse outcomes. We have previously shown, in retrospective data, that prior chemotherapy increases the incidence of clonal hematopoiesis (CH), especially in DNA damage response (DDR) pathway genes including TP53, PPM1D, and CHEK2 and is associated with progression to tMN. In particular, patients who receive PARPi therapy are more likely to have CH compared to other therapies or untreated patients. In the IMPACT study of CH in 10,156 cancer patients, exposure to PARPi were more likely to have CH (33%) compared to untreated patients (16%). This was particularly pronounced for DDR gene mutations, with 25% of PARPi treated patients with DDR CH compared to 2% of untreated patients. In multivariate analysis accounting for demographics and exposure to other chemotherapy or radiation therapy, exposure to PARPi conferred an increased risk of DDR CH (OR = 3.6, 95% CI 1.5-8.5, p = 0.004). From these data, we hypothesize that mutations in DDR pathway genes provide a fitness advantage to hematopoietic stem/progenitor cells (HSPCs) following PARPi treatment, leading to clonal hematopoiesis. A major limitation, however of our previous work in retrospective clinical samples, is the inability to completely adjust for the confounding effect of prior exposure to cytotoxic therapy (in particular platinum therapies) and germline BRCA1/2 mutations; both which have been shown or hypothesized to increase the risk of tMN. To test whether PARPi exposure might provide a fitness advantage to HSPCs independent of prior exposure to other therapies, we first examined the response of CRISPR-gene edited TP53-/- MOLM13 cells to the PARPi Olaparib and, as a control, Cisplatin. As expected, TP53-/- cells had increased resistance to both agents, though the response was much more pronounced in Cisplatin-treated cells (Figure 1A,B). Next, we implemented a mouse model of TP53-mutant clonal hematopoiesis, by generating mixed bone marrow chimeras transplanted with a 1:9 ratio of wildtype (CD45.1) to TP53 R172H+/- (CD45.2) cells. The "baseline" contribution of TP53 R172H+/- (CD45.2) cells to peripheral blood leukocytes 8 weeks after transplantation was determined by flow cytometry. Mice were then randomized into the following three cohorts: 1) Cisplatin (6mg/kg on days 1, 8, and 15); 2) Olaparib (50mg/kg daily for 3 weeks); and 3) vehicle alone. Peripheral blood chimerism was assessed 3, 9, and 12 weeks after initiating treatment. In addition, the contribution of TP53 R172H+/- to lineage -Sca1 +Kit + (LSK) cells in the bone marrow was determined. Cisplatin treatment resulted in a significant increase in the contribution of TP53 R172H+ to peripheral blood total leukocytes, granulocytes, and bone marrow LSK cells (Figure 1C-E). In contrast, Olaparib treated mice showed no change in CD45 chimerism. From these results we conclude that p53-deficiency does not confer a strong fitness advantage to mouse HSPCs in response to PARPi treatment. This suggests that the strong association observed between prior PARPi therapy, CH and tMN in clinical cohorts may in part be due to the confounding effects of prior (often heavy) exposure to platinum-based therapy. However, the majority of patients receiving PARPi have germline heterozygous BRCA1/2 mutations that could be contributing to their hematopoietic response to PARPi therapy. Experiments are underway to test this possibility by analyzing mixed bone marrow chimeras carrying heterozygous mutations of both Brca1 and Trp53. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Inferior Outcomes of Patients with Quad and Penta-Refractory Multiple Myeloma (MM) Compared to Those of Patients Who Have Been Quad and Penta Exposed

Background: Despite significant advancements in MM therapies, patients with quad-refractoriness (refractory to proteasome inhibitors: bortezomib and carfilzomib, and immunomodulatory drugs: lenalidomide and pomalidomide) and penta-refractoriness (additional refractoriness to CD-38+ monoclonal antibody daratumumab) have a poor prognosis in terms of short progression-free survival (PFS) and overall survival (OS). This is a retrospective, single institutional study comparing the outcomes of patients with quad and penta-refractory MM to patients who were quad and penta-exposed, but not refractory. Methods: Consecutive patients from the John Theurer Cancer Center at Hackensack Meridian School of Medicine who were quad and penta-exposed and/or refractory between the dates of 1/1/2015 and 3/1/2021 were identified. Quad-exposed was defined as having had prior exposure to bortezomib, carfilzomib, lenalidomide and pomalidomide. Penta-exposed was defined as having prior exposure to bortezomib, carfilzomib, lenalidomide and pomalidomide and daratumumab. Penta or quad refractory was defined as having stable disease (as best response) or progressive disease while on all of the above drugs, per International Myeloma Working Group (IMWG) definition of refractory. Patients were excluded if they had missing data or if they did not meet the above definitions. Baseline characteristics, high-risk status, ISS, treatment history, treatment response, drugs at first relapse and survival outcomes were obtained retrospectively from the electronic medical record and entered into database. High-risk cytogenetics were defined as the presence of t(4;14), t(14;16) or del 17p; 1q21 gain or amplification; 1p del; t(6;14); t(14;20). Baseline patients' characteristics were summarized descriptively by quad and penta-exposed groups. PFS and OS were estimated using the Kaplan-Meier method. Univariate and multivariable adjusted Cox proportional hazard regression models examined factors affecting OS. Results: A total of 162 patients met the inclusion criteria: 18/162 (11%) were quad or penta-exposed, 32/162 (20%) were quad-refractory, and 112/162 (69%) were penta-refractory. Median age was 62 (55-69), IgG subtype (59%), and 62/162 (38.5%) had high-risk cytogenetics. The median number of lines prior was 6 (range 4-8) among all patients, and 7 (range 5-9) in the penta-refractory group. 133/162 (82.1%) had prior autologous-stem cell transplant (ASCT). Extramedullary disease was present in 40/162 (25.2%). Plasma cell leukemia was present in 14/162 (8.8%). For those who were penta-refractory, the median time from quad to penta-refractory status was 10.2 months (95% confidence interval (CI), 3.57-16.57). See Table 1. Figure 1 shows PFS and OS from the time of becoming quad or penta-exposed or refractory (T0 ). The median PFS after T0 was 11.86 months (95% CI, 6.5-26.6) for combined quad and penta-exposed, compared to 3.88 months (95% CI, 2.99-5.17) for quad and penta-refractory patients. With a median follow-up of 5.14 months (Range, 0-52.4), the median OS for all patients was 7.43 months (95% CI, 5.8- 12.94). (Figure 1A). With a median follow-up time of 4.45 months (Range, 0-52.38), the median OS for patients who were quad or penta-refractory was 5.97 months [95% CI. 4.44-8.23], compared to OS not reached (NR) for quad or penta-exposed, with a median follow-up of 11.86 months. (Figure 1B). At least one subsequent treatment regimen was employed after T0 in 85% of the patients. (Figure 1C). Multivariable adjusted analysis (Table 2) revealed that patients ≥62 had inferior OS compared to those < 62 (p -value=0.046). Furthermore, patients who had ≤10 months between becoming quad- and penta-refractory had inferior OS compared to patients with >10 months (p=0.031). OS was not significantly affected by high risk versus standard cytogenetics or drugs used at first relapse. Conclusion: MM patients with quad and penta-refractory disease have significantly worse outcomes compared to patients with quad and penta-exposed MM: older age (> 62 years) and a short interval (< 10 months) between becoming quad and penta-refractory confer an adverse prognosis. Prospective studies are required to confirm these findings. Penta and quad-refractory multiple myeloma continues to represent a vulnerable population with an unmet need for therapeutic approaches. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Effects of Prior Exposure to Tec Kinase(BTK/ITK) Inhibitors on Kte-X19 Products

Introduction: Frequent and durable responses were recently reported in relapsed or refractory (R/R) mantle cell lymphoma (MCL) patients treated with KTE-X19, an autologous CD19-targeted chimeric antigen receptor-engineered T-cell (CAR-T) product (Wang et al. N Engl J Med. 2020). Most patients enrolled had received at least one line of Tec kinase inhibitor prior to KTE-X19 manufacturing, either in the form of ibrutinib, a Bruton's tyrosine kinase (BTK) and Inducible T cell kinase (ITK) inhibitor, or acalabrutinib, a more selective BTK inhibitor. Pharmacokinetic expansion of KTE-X19 was higher in ibrutinib-treated patients relative to acalabrutinib-treated patients. We previously showed that prolonged exposure to ibrutinib enhanced T cell effector function and proliferation in patients with CLL (Fraietta et al, Blood, 2016). To assess the impact of Tec kinase inhibitor on KTE-X19 products and downstream clinical outcomes, we examined the phenotype, transcriptional profile and cytokine production of KTE-X19 infusion products and post-infusion lymphocytes from patients with R/R MCL treated on the Zuma-2 study. Study Design and Methods: We evaluated biospecimens from MCL patients who enrolled on the Zuma-2 clinical trial (NCT02601313) and who were previously treated with ibrutinib (n=14) or acalabrutinib (n=6). Samples analyzed consisted of KTE-X19 CAR T products and peripheral blood mononuclear cells (PBMC) collected 7 days after infusion. Lymphocytes were assessed for CAR expression, T cell phenotype, transcriptional profile and cytokine production. In addition, CAR T cell phenotypes and cytokines were profiled following co-culture of KTE-X19 with CD19 + Toledo cells (DLBCL). Results: Flow cytometric analysis of KTE-X19 demonstrated similar distributions of CD4+ and CD8+ T cells and comparable frequencies of central and effector memory populations in the CAR+ T cells derived from patients with prior exposure to ibrutinib vs. acalabrutinib. T helper subset analysis trended towards enrichment of Th1/Th17 populations within the CAR+ CD4+ cells of the ibrutinib cohort. This finding was further supported by transcriptional profiling of sorted CAR+ T cells from infusion products, where Th1/Th17, Jak/STAT and activation-related genes were enriched in the cohort with prior ibrutinib exposure. In addition, the Th1 phenotype was more frequent in PBMC of ibrutinib-exposed patients (8/14) compared to acalabrutinib-exposed patients (1/4). Interestingly, a shift from a central memory-dominant product towards an effector memory phenotype was observed in peripheral CD4+ and CD8+ CAR T cells in the ibrutinib cohort, whereas acalabrutinib post-infusion CAR T cells maintained a central memory phenotype. In vitro stimulation of KTE-X19 CAR-T infusion products with tumor cells resulted in a significant enrichment of the Th1 population in patients who had received ibrutinib compared to those that received acalabrutinib (p=0.0058). Following stimulation, CAR-T cells from the acalabrutinib cohort produced higher levels of Th2 cytokines, including IL-4, IL-5, and IL-13 as well as GM-CSF compared to the ibrutinib cohort. Conclusions: Analysis of KTE-X19 infusion products and day 7 post-infusion PBMC demonstrated that CAR T cells from patients with prior ibrutinib exposure have a Th1 predominant phenotype, suggesting that ibrutinib but not acalabrutinib promotes Th1 differentiation and effector function, potentially through the inhibition of ITK. Furthermore, our data suggest that inhibition of non-BTK targets such as ITK may play a role in driving a Th17 phenotype. Prior exposure to ibrutinib may increase CAR T cell effector function to a greater extent than exposure to acalabrutinib to enhance clinical outcome in patients with MCL. Disclosures Budka: Kite Pharma: Current Employment. Sowrirajan: Kite Pharma: Current Employment. Nguyen: Kite Pharma: Current Employment. Shen: Gilead Sciences: Current equity holder in publicly-traded company; Kite, a Gilead Company: Current Employment, Other: Leadership role, Patents & Royalties; Atara: Current Employment, Current equity holder in publicly-traded company, Other: Leadership role, Patents & Royalties. Bot: Kite, a Gilead Company: Current Employment; Gilead Sciences: Consultancy, Current equity holder in publicly-traded company, Other: Travel support. Maus: Agenus: Consultancy; Arcellx: Consultancy; Astellas: Consultancy; AstraZeneca: Consultancy; Atara: Consultancy; Bayer: Consultancy; BMS: Consultancy; Cabaletta Bio (SAB): Consultancy; CRISPR therapeutics: Consultancy; In8bio (SAB): Consultancy; Intellia: Consultancy; GSK: Consultancy; Kite Pharma: Consultancy, Research Funding; Micromedicine: Consultancy, Current holder of stock options in a privately-held company; Novartis: Consultancy; Tmunity: Consultancy; Torque: Consultancy, Current holder of stock options in a privately-held company; WindMIL: Consultancy; Adaptimmune: Consultancy; tcr2: Consultancy, Divested equity in a private or publicly-traded company in the past 24 months; century: Current equity holder in publicly-traded company; ichnos biosciences: Consultancy, Current holder of stock options in a privately-held company.

Antibody Response after Vaccination for Sars-Cov-2 in Patients with AL Amyloidosis and the Impact of Therapy

Patients with lymphoproliferative disorders are at high risk for severe COVID-19. For patients with AL amyloidosis, in which there is also critical organ involvement, this risk may be even higher. Vaccination against SARS-CoV-2 is the best strategy to avoid severe COVID-19, but response to vaccines may be compromised in patients with B-cell lymphoproliferative or plasma cell malignancies, as in AL amyloidosis. Although modest in size, the plasma cell clone in AL may cause immunosuppression while anticlonal therapies further compromise immune responses. To evaluate immunization efficacy, we measured the titers of neutralizing antibodies (NAbs) against SARS-CoV-2 after vaccination with BNT162b2 in patients with AL amyloidosis. As a control group we used volunteers, matched (ratio 1:2) for age and gender, who had no autoimmune or active malignant or infectious disease. Serum was separated within 4 hours from blood collection and stored at -80°C until the day of measurement on (A) day 1 (D1; before the first dose of BNT162b2) (B) day 22 (D22; before the 2nd dose) and (C) day 50 (D50; ie 30 days after the 2nd dose). NAbs against SARS-CoV-2 were measured using FDA approved methodology (cPass™ SARS-CoV-2 NAbs Detection Kit; GenScript, Piscataway, NJ, USA). According to the manufacturer of the assay, a titer ≥ 50% is considered a clinically relevant threshold for viral inhibition. The study included 144 patients with AL amyloidosis, of which 120 had NAbs titers assessed on all time points and were included in the final analysis (53% males; median age: 66, IQR: 57-72 years) and 240 matched controls (53% males; median age: 66, IQR: 57-72 years). 66 (55%) AL patients were on active therapy, 17.5% were on daratumumab (DARA)-based therapy, 52 (43%) had discontinued therapy >3 months from the date of the first shot, 19% had prior exposure to DARA and 94 (78%) were in hematologic remission (CR or VGPR). Prior to the 1st dose (D1), NAb titers were similar between patients and controls (median 14.9% (IQR 7.8-23.1%) vs 14% (IQR 6.8-22.9%), p=0.439); 6 AL patients had baseline NAbs >50%, of which 5 reported a history of COVID-19 infection. On D22, there was a significant increase of NAbs titers both in controls and AL patients (both p<0.001); however, median NAb titer was 23.6% (IQR 12.4-37.7%) in AL patients vs 47.5% (IQR 32.1-62.7%) in controls (p<0.001) and 20.5% of AL patients vs 46.7% of controls (p<0.001) developed NAb titers ≥50%. On D50, there was further increase in NAbs titers both in controls and AL patients (both p<0.001) and median NAb titer for AL patients was 83.1% (IQR 41.5-94.9%) vs 95.6% (IQR 91.7-97.2%) in controls (p<0.001); 71% of AL patients vs 98% of matched controls (p<0.001) developed NAb titers ≥50%. Among AL patients, factors associated with NAb titers on D50 included age (p<0.001), lymphocyte counts (p<0.001), serum albumin (p<0.001) and amount of proteinuria at the time of vaccination (p=0.047), renal involvement (p=0.047), use of steroids (p<0.001), active treatment (p<0.001), treatment-free interval (p=0.001), remission status (CR/VGPR) (p=0.018). There was no significant association with gender (p=0.092), BMI (p=0.198), IgG (0.099), IgA (p=0.789) or IgM levels (p=0.687), liver (p=0.521) or heart involvement (p=0.141). Patients on therapy had lower NAb titers at D50 (median 50.1% (IQR 25.3-84.1%) vs 91.6% (IQR 74.5-96.5%) for those not on treatment, p<0.001), so that 51% had a D50 NAb titer ≥50% vs 87% of those not on therapy. Current DARA therapy (median 52.1% vs 46.4% without DARA, p=0.486) or prior exposure to DARA (92.1% vs 91.2%, p=0.966) were not associated with D50 NAb titers. Generalized linear models were used for evaluation of multiple factors associated with D50 NAb titers: at least 3 months since the last dose of anticlonal therapy (p<0.001), lymphocyte counts (p=0.001) and serum albumin levels at the time of vaccination (p=0.020) were independent predictors of NAb titers on D50. When seroconversion was defined as a NAb titer ≥50% at D50, then >3 months of treatment-free interval (HR:7.75, p<0.001,) was the strongest factor associated with seconversion. In conclusion, patients with AL amyloidosis have an attenuated response to vaccination with BNT162b2 especially among those on active therapy or with less than 3 months since the last dose of treatment. For such patients, an anamnestic dosing strategy could be considered, especially after completion of anticlonal therapy. Figure 1 Figure 1. Disclosures Kastritis: Genesis Pharma: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding. Terpos: Novartis: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Genesis: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; BMS: Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; GSK: Honoraria, Research Funding. Gavriatopoulou: Sanofi: Honoraria; GSK: Honoraria; Karyopharm: Honoraria; Takeda: Honoraria; Genesis: Honoraria; Janssen: Honoraria; Amgen: Honoraria. Dimopoulos: Amgen: Honoraria; BMS: Honoraria; Janssen: Honoraria; Takeda: Honoraria; BeiGene: Honoraria.

Sars-CoV2 Antibody Responses in Patients with Hematological Malignancies Following Anti-CD20 Therapy

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with increased mortality in patients with hematological malignancies, with increase rates between 33-37%. Vaccination against SARS-CoV-2 have shown efficacy decreasing infection rates, with efficacy rates of 50-95%. However, the immunogenicity in immune-compromised patients, particularly those with prior exposure to anti-CD20 antibodies and duration of protective immunity, remains unknown. The current guidelines recommend vaccination for all patients receiving cancer therapy with a 3 months delay following hematological stem cell transplant and CAR-T cell therapy. Methods: We performed a retrospective analysis of the efficacy of SARS-CoV-2 vaccination in patients with hematological malignancies following anti-CD20 therapy. Adult patients, 18 years and older, with frontline and relapsed hematological malignancies were included. We performed a chart review to obtain treatment responses and analyze the correlation between clinical, biological, and demographic characteristics and antibody titer responses. SARS-CoV-2 antibodies were measure by qualitative IgG antibody analysis, SARS-CoV-2 Semi-Quantitative total antibodies and SARS-CoV-2 IgG antibody spike. Comparative analysis of response with a control group of patients with hematological malignancies with no prior exposure to anti-CD20 therapy was performed. Results: A total of 29 patients (pts) were included. Twenty-five pts (86%) were >65 years, with a median age of 73 years (49-93). Most patients were female (52%) with a diagnosis of non-Hodgkin Lymphoma (NHL) (86%). Twenty-four (83%) had rituximab therapy, and six pts (21%) had received Obinutuzumab. Baseline characteristics are listed in Table 1. Seventeen pts had completed treatment by the time of vaccination (59%), included 16 pts (55%) without any anti-CD20 therapy in the last 12 months. Four pts (14%) had common variable immunodeficiency (CVID). Most pts received the Pfizer vaccine (83%), while 6% were given the Moderna vaccine and 3% J&J vaccine. The median time from last anti-CD20 therapy and SARS-CoV-2 antibody testing was 13 months (0-156). SARS-CoV-2 antibodies following vaccination were assessed after a median of 1.6 months (range 0.2-5 months). Overall a total of 44 measurements were done with a median of 1 assessment per patient (range 1-3). With a median follow-up of 1.6 months from completion of vaccination, the overall response rate was 35%, with response rates of 24% for recent anti-CD20 exposure (< 12 months) vs. 44% for patients with no exposure in the last 12 months. Response rates are listed in Figure 1.Figure 2 compares antibody titers distribution among hematological malignancy pts with a history of anti-CD20 therapy vs. the control group. The median SARS COV2 IgG Spike titers were 0.9 for the anti-CD20 subgroup vs. 4.9 in the control group (P=0.02). Only two patients had sequential vaccination with Pfizer and Moderna vaccines; however, neither developed antibodies despite re-vaccination. We did not identify any pts with a production of late antibody titers among pts with prior anti-CD20 exposure. Response rates were significantly decreased among pts with prior anti-CD20 exposure with ORR 35% vs. 65% for pts with hematological malignancies without anti-CD20 treatment (P=0.002) We performed univariate analysis to determine the clinical factors associated with increased response rates. We found that decreased ALC counts were associated with decreased responses, while patients with no anti-CD20 therapy in the last 24 months were more likely to respond. There were no cases of COVID-19 infection following vaccination irrespective of titer responses. Conclusions: While SARS-CoV-2 vaccination has shown to be effective and induces response rates from 50-95%, we found decreased response rates among immunocompromised cancer patients, particularly among those with anti-CD20 therapy. Responses were associated with absolute lymphocyte count and time from monoclonal therapy, with patients with normal levels and no therapy for over two years most likely to respond. However, despite low response rates, there were no cases of COVID-19 infection in our study. Further, follow-up is needed to determine the duration of response and persistence of antibodies. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.