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Background: Despite the transformative potential of chimeric antigen receptor T (CAR-T) therapy, more tools to assist with identifying patients with increased likelihood of benefitting from this therapy will be helpful, particularly given the logistical complexity and socio-economic demands for CAR-T relative to other therapies. Health care resource restriction during the COVID-19 pandemic highlights the need for these tools. We present a simple survival score that uses 3 readily available clinical labs: platelet (plt), absolute lymphocyte count (ALC), and Lactate dehydrogenase (LDH), to predict the risk of dying within 6 months of CAR-T therapy in patients with aggressive lymphoma. Method(s): We conducted a retrospective chart review of patients with aggressive non-Hodgkin lymphoma (NHL) who received FDA-approved CAR-T between Jan 2018 to Jan 2022 at Mayo Clinic Rochester.(Table Presented)Results: Among a total of 110 pts who received CAR-T, 27 (25%) pts died within the first 6 months post CAR-T infusion (OS <= 6 months). Disease progression was the main cause of death (18/25, 72%), followed by infection (4/25, 16%), CAR-T related (HLH/MAS, 2/25, 8%), second primary malignancy (1/25, 4%) and unknown (2/25, 8%).Baseline demographics were comparable between the OS>6months and <=6months groups (Table 1). Patients' ECOG, Karnofsky performance status and 11 labs at the time of evaluation for CAR-T therapy (initial eligibility assessment, prior to leukapheresis) were compared between those who died from any cause within 6 months of CAR-T infusion and those who did not. Hemoglobin, plt, ALC, absolute monocyte count, CRP, ferritin, and LDH were selected as clinically and/or statistically significant variables for multivariate testing. Multivariate regression with boot-strap testing identified plt, ALC, and LDH as the most predictive variables with 80.9+/-11.7% accuracy for predicting death within 6 months of CAR-T infusion. Patients were scored 0-3 using these 3 labs, with 1 point assigned for plt <= 100 X109/L, ALC <= 0.4 X109/L, or LDH > 222 U/L (upper limit of normal). OS by this survival score is shown in Figure 1.(Figure Presented)Discussion: Due to the curative potential of CAR-T, patients with broader characteristics than those treated on registration studies have been treated in standard of care practice. While an estimated 5%-10% risk of CAR-T associated deaths in the first 3 months is seen across all patients in clinical trials, predictors for early death after CAR-T in real-world patient populations can provide additional context for pts and providers when selecting treatment. This survival score is important proof of concept that a simple model using readily accessible clinical labs at the time of CAR-T evaluation could provide additional context to help with additional clinical decision-making. Multicenter prospective studies will help define and validate the definitive survival scoring system.Copyright © 2023 American Society for Transplantation and Cellular Therapy
RESUMEN
Background: Pts with previously treated R/R aggressive LBCL have compromised health-related QOL (HRQOL). Liso-cel is an autologous, CD19-directed, defined composition, 4-1BB CAR T cell product administered at equal target doses of CD8 + and CD4 + CAR + T cells. In a prespecified interim analysis of TRANSFORM (NCT03575351), a randomized, open-label, pivotal trial, liso-cel demonstrated statistically significant and clinically meaningful improvement in the primary endpoint of event-free survival and key secondary endpoints (complete response rate and progression-free survival) in adults with R/R LBCL after failure of first-line (1L) immunochemotherapy compared with SOC, with no new safety signals. Here we present results of the pt-reported outcomes (PRO) analysis from TRANSFORM. Methods: Adults (age ≤ 75 yrs) with R/R LBCL (≤ 12 mo after 1L therapy), who were eligible for autologous stem cell transplantation (ASCT), were randomized to receive either SOC (3 cycles of salvage chemotherapy [CT] and BEAM + ASCT for responding pts) or liso-cel after lymphodepletion. Crossover to receive liso-cel was allowed in the SOC arm for pts who failed treatment. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - 30 items (EORTC QLQ-C30) and the Functional Assessment of Cancer Therapy - Lymphoma Subscale (FACT-LymS) were administered at randomization (baseline) and on Days 29 (infusion of liso-cel or 2 cycles of salvage CT), 64 (1 mo post liso-cel or completion of CT), 126 (3 mos post liso-cel or 2 mos post ASCT), and Mo 6 and other prespecified timepoints up to Mo 36 or end of study. No PRO data were collected after crossover. The analysis was based on the PRO-evaluable population (pts with a baseline and ≥ 1 post-baseline assessment). Predefined thresholds determined clinically meaningful changes. Global health/QOL (GH/QOL), physical functioning, cognitive functioning, fatigue, pain, and FACT-LymS were the primary domains of interest based on their relevance to the study population and treatment. A linear mixed model for repeated measures (MMRM) analysis was performed to assess the between-treatment difference in overall least squares (LS) mean change from baseline for each primary domain, using data collected up to Day 126 for visits with a sample size per arm ≥ 10. Proportions of pts with meaningful change from baseline were assessed for each primary domain up to Mo 6. All analyses were descriptive only. Results: Of 184 randomized pts, 90 (49%) and 85 (46%), respectively, were included in the PRO-evaluable population for the EORTC QLQ-C30 (SOC vs liso-cel n=43 vs 47) and FACT-LymS (n=40 vs 45, respectively). The PRO assessment completion rate from baseline up to Mo 6 was ≥ 45%, which was lower than expected primarily due to operational challenges during the COVID-19 pandemic but was comparable for both arms. In the MMRM analysis, the liso-cel arm had more favorable overall LS mean changes from baseline to Day 126 than the SOC arm in most of the EORTC QLQ-C30 domains and FACT-LymS. In particular, the between-treatment differences for cognitive functioning (−2.09 vs 2.21) and fatigue (3.75 vs −1.95) for SOC versus liso-cel, respectively, exceeded the prespecified minimal important difference threshold (Table);in those domains, the SOC arm deteriorated while the liso-cel arm improved. In individual-level analyses, the proportion of pts with meaningful improvement for fatigue and GH/QOL was higher, while deterioration was lower, in the liso-cel arm versus SOC arm from baseline up to Mo 6 (Figure). At Mo 6, a higher proportion of pts experienced worsened fatigue (71% vs 18%) and a lower proportion experienced improved fatigue (29% vs 47%) in the SOC arm compared with the liso-cel arm;for GH/QOL, a higher proportion of pts worsened (57% vs 18%) and lower proportion improved (14% vs 53%), respectively. For the other primary domains, the proportions of pts with improvement or deterioration favored liso-cel or were similar between arms. Conclusions: Compared with SOC, liso-cel sh wed favorable improvement in most primary PRO domains, particularly EORTC QLQ-C30 cognitive functioning and fatigue and more pts showed PRO improvements and fewer showed deterioration by Mo 6 with liso-cel. The results were achieved despite only responders remaining in the SOC arm after salvage CT. HRQOL was either improved or maintained after liso-cel treatment in pts with R/R LBCL after failure of 1L therapy. [Formula presented] Disclosures: Abramson: Bristol-Myers Squibb Company: Consultancy, Research Funding;Morphosys: Consultancy;C4 Therapeutics: Consultancy;Kite Pharma: Consultancy;Kymera: Consultancy;Incyte Corporation: Consultancy;Bluebird Bio: Consultancy;Astra-Zeneca: Consultancy;Allogene Therapeutics: Consultancy;Novartis: Consultancy;EMD Serono: Consultancy;Genmab: Consultancy;Seagen Inc.: Research Funding;AbbVie: Consultancy;Karyopharm: Consultancy;Genentech: Consultancy;BeiGene: Consultancy. Arnason: Juno/BMS: Honoraria. Glass: BMS: Consultancy;Roche: Consultancy, Research Funding, Speakers Bureau;Riemser: Research Funding;Kite: Consultancy;Novartis: Consultancy;Helios Klinik Berlin-Buch: Current Employment. Crotta: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Montheard: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Previtali: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Liu: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Braverman: BMS: Current Employment, Current equity holder in publicly-traded company. Guo: Daiichi Sankyo: Consultancy;UCB: Consultancy;Janssen: Consultancy;Gilead: Consultancy;Bristol Myers Squibb: Consultancy;EMD Serono: Consultancy;Evidera: Current Employment. Shi: Bristol Myers Squibb: Consultancy. Kamdar: ADC Therapeutics: Consultancy;Adaptive Biotechnologies: Consultancy;TG Therapeutics: Research Funding;Genentech: Research Funding;AbbVie: Consultancy;KaryoPharm: Consultancy;Kite: Consultancy;AstraZeneca: Consultancy;SeaGen: Speakers Bureau;Celgene: Other;Genetech: Other;Celgene (BMS): Consultancy.
RESUMEN
Background:COVID-19 adversely affects individuals with cancer. Several studies have found that seroconversion rates among patients with hematologic malignancies are suboptimal when compared to patients without cancer. Among patients with hematologic malignancies, seroconversion rates also appear to be influenced by recent treatment and the type of treatment they have received. Patients with non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) are immunocompromised due to impaired humoral and cellular immunity in addition to prescribed immunosuppressive therapy. Chimeric antigen receptor T-cell (CAR T) therapy is now widely used for NHL and MM, but little is known about seroconversion rates after COVID-19 vaccination among these populations. Current national guidelines recommend COVID-19 vaccination to be offered to CAR T recipients as early as three months thereafter. We retrospectively evaluated SARS-CoV-2 spike-binding IgG antibody levels following COVID-19 vaccination among NHL and MM CAR T therapy recipients. Methods:This retrospective study was conducted at three Mayo Clinic sites on NHL and MM patients that received CAR T infusions from Sept 2016 to June 2021. Baseline characteristics were ascertained from medical records. All NHL and MM patients who had received CAR T at any point and were alive at the time that the COVID-19 vaccine first became available were eligible for inclusion for antibody response evaluation. For antibody response to vaccination, antibody spike values > 0.80 U/mL were considered positive. Results: Out of 104 CAR T infusions, 73 patients are alive at the time of this submission. We have had 7 patients with known COVID-19 pre-CAR T and all 7 are currently alive (5 have antibody titers and 2 have not been tested yet). Nineteen patients developed known COVID infection post-CAR T (13 alive and 6 deceased). The mortality of COVID post-CAR T in our sample was 31.5%. Furthermore, of the 13 patients that survived COVID-19, they received CAR T an average of 416 days prior to COVID-19 infection (median = 337, range = 54 - 1406);the 6 patients who died from COVID-19 had received CAR T an average of 250 days prior to COVID-19 infection (median = 164, range = 7 - 846). All 6 deceased patients did not receive COVID-19 vaccination pre-CAR T. Out of 17 CAR T patients tested for antibody spike titers post COVID-19 vaccination, 76.4% were able to mount an antibody response. More patients with MM had a higher titer response to the vaccine (>250 U/mL) compared to the NHL counterparts (0.80-249 U/mL). All patients that received the vaccine, regardless of antibody response, were alive at the time of this submission. Conclusions:The majority of CAR T recipients with NHL and MM are able to mount an antibody response following COVID-19 vaccination in our relatively small sample. The frequency of seroconversion among CAR T recipients seems to be similar to patients with hematologic malignancy who had received a hematopoietic cell transplant reported elsewhere. These findings are limited by our small sample size and may be influenced by the timing of vaccination relative to CAR T. Furthermore, almost half of our patients received IVIG post CAR T which could potentially cause false positive antibody results as pooled immunoglobulin preparations may contain COVID-19 antibodies from vaccinated healthy donors. To better understand the characteristics of the immunologic response against SARS-CoV-2 in patients post-CAR T, larger multicenter studies exploring both humoral and cellular immunity will be needed. JEWN, MI and JM are co-first authors and PV, HM and AR are co-senior authors. [Formula presented] Disclosures: Munoz: Physicians' Education Resource: Honoraria;Seattle Genetics: Honoraria;Bayer: Research Funding;Gilead/Kite Pharma: Research Funding;Celgene: Research Funding;Merck: Research Funding;Portola: Research Funding;Incyte: Research Funding;Genentech: Research Funding;Pharmacyclics: Research Funding;Seattle Genetics: Research Funding;Janssen: Research Funding;Millennium: Research Funding;Gilea /Kite Pharma, Kyowa, Bayer, Pharmacyclics/Janssen, Seattle Genetics, Acrotech/Aurobindo, Beigene, Verastem, AstraZeneca, Celgene/BMS, Genentech/Roche.: Speakers Bureau;Pharmacyclics/Abbvie, Bayer, Gilead/Kite Pharma, Pfizer, Janssen, Juno/Celgene, BMS, Kyowa, Alexion, Beigene, Fosunkite, Innovent, Seattle Genetics, Debiopharm, Karyopharm, Genmab, ADC Therapeutics, Epizyme, Beigene, Servier: Consultancy;Targeted Oncology: Honoraria;OncView: Honoraria;Kyowa: Honoraria. Bergsagel: Oncopeptides: Consultancy, Honoraria;Novartis: Consultancy, Honoraria, Patents & Royalties: human CRBN mouse;Pfizer: Consultancy, Honoraria;Celgene: Consultancy, Honoraria;Janssen: Consultancy, Honoraria;Genetech: Consultancy, Honoraria;GSK: Consultancy, Honoraria. Wang: Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding;LOXO Oncology: Membership on an entity's Board of Directors or advisory committees, Research Funding;Genentech: Research Funding;InnoCare: Research Funding;Novartis: Research Funding;MorphoSys: Research Funding;Eli Lilly: Membership on an entity's Board of Directors or advisory committees;TG Therapeutics: Membership on an entity's Board of Directors or advisory committees. Fonseca: Juno: Consultancy;Kite: Consultancy;Aduro: Consultancy;OncoTracker: Consultancy, Membership on an entity's Board of Directors or advisory committees;GSK: Consultancy;AbbVie: Consultancy;Patent: Prognosticaton of myeloma via FISH: Patents & Royalties;Caris Life Sciences: Membership on an entity's Board of Directors or advisory committees;Scientific Advisory Board: Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees;BMS: Consultancy;Amgen: Consultancy;Sanofi: Consultancy;Merck: Consultancy;Mayo Clinic in Arizona: Current Employment;Celgene: Consultancy;Takeda: Consultancy;Bayer: Consultancy;Janssen: Consultancy;Novartis: Consultancy;Pharmacyclics: Consultancy. Palmer: Sierra Oncology: Consultancy, Research Funding;CTI BioPharma: Consultancy, Research Funding;Protagonist: Consultancy, Research Funding;Incyte: Research Funding;PharmaEssentia: Research Funding. Dingli: Novartis: Research Funding;GSK: Consultancy;Apellis: Consultancy;Alexion: Consultancy;Sanofi: Consultancy;Janssen: Consultancy. Kapoor: Sanofi: Research Funding;AbbVie: Research Funding;Takeda: Research Funding;Karyopharm: Consultancy;Cellectar: Consultancy;BeiGene: Consultancy;Pharmacyclics: Consultancy;Sanofi: Consultancy;Amgen: Research Funding;Ichnos Sciences: Research Funding;Regeneron Pharmaceuticals: Research Funding;Glaxo SmithKline: Research Funding;Karyopharm: Research Funding. Kumar: Roche-Genentech: Consultancy, Research Funding;Oncopeptides: Consultancy;Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;BMS: Consultancy, Research Funding;Beigene: Consultancy;Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding;Novartis: Research Funding;Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding;Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Tenebio: Research Funding;Merck: Research Funding;Carsgen: Research Funding;KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Amgen: Consultancy, Research Funding;Bluebird Bio: Consultancy;Antengene: Consultancy, Honoraria;Sanofi: Research Funding. Paludo: Karyopharm: Research Funding. Bennani: Kymera: Other: Advisory Board;Vividion: Other: Advisory Board;Kyowa Kirin: Other: Advisory Board;Daichii Sankyo Inc: Other: Advisory Board;Purdue Pharma: Other: Advisory Board;Verastem: Other: Advisory Board. Ansell: Bristol Myers Squibb, ADC Therapeutics, Seattle Genetics, Regeneron, Affimed, AI Therapeutics, Pfizer, Trillium and Takeda: Research Funding. Lin: Kite, a Gilead Company: Consultancy, Research Funding;Merck: Research Funding;Gamida Cell: Consultancy;Takeda: Research Funding;Juno: Consultancy;Bluebird Bio: Consultancy, Research Funding;Celgene: Consultancy, Research Funding;Novartis: Consultancy;Janssen: Consultancy, Research Funding;Sorrento: Consultancy;Legend: Consultancy;Vineti: Consultancy. Murthy: CRISPR Therapeutics: Research Funding.