ABSTRACT
Background: Ide-cel, a BCMA directed CAR T-cell therapy, was FDA approved 3/26/2021 for the treatment of RRMM after 4 prior lines of therapy. We evaluated the real-world outcomes of patients treated with standard of care ide-cel under the commercial FDA label. Methods: Ten US academic centers contributed data to this effort independent of the manufacturer. As of 1/10/2022, 138 patients were leukapheresed with overall manufacturing failure in 6 (4%). 108 patients were infused ≥ 30 days prior to data-cut off and constitute the study population for this retrospective analysis. Results: Table describes the study population compared to the pivotal KarMMa-1 trial (Munshi et al, NEJM 2021). Patients in our study were less likely to have ECOG PS of 0/1 (77%) and more likely to be penta-refractory (41%). 67% of patients would not have met eligibility criteria for KarMMa. Common reasons for ineligibility (> 1 reason in 22% patients) were co-morbidities (28%), cytopenias (22%), prior therapy with alloSCT/ CAR-T/other BCMA therapy (19%), CNS myeloma/non-measurable disease/plasma cell leukemia (13%), and fitness (12%). 81% of patients received bridging therapy. Toxicity was comparable to that seen in KarMMa-1. Cytokine release syndrome (CRS) was seen in 82% (> grade 3: 4%) and immune effector cell-associated neurotoxicity syndrome (ICANS) in 15% (> grade 3: 5%) of patients, respectively. Tocilizumab and steroids were used in 72% and 25% of patients, respectively. Infections were seen in 34% of patients. Day 30 response was evaluable in 104 patients. Response rates were: ≥ partial response, 83%;≥ very good partial response, 64%;and ≥ complete response (CR), 34%. 11% of patients have died by data cut-off, 7 due to disease progression and 5 due to other causes (1 grade 5 CRS, 1 hemophagocytic lymphohistiocytosis, 1 progressive neurological weakness, 2 COVID-19). Conclusions: This multicenter retrospective study delineates the real-world outcomes of ide-cel CAR T-cell therapy for RRMM. Despite more patients being penta-refractory and less fit compared to the pivotal KarMMa trial, safety and 30-day responses in the real-world setting (overall response rate: 83%, CR: 34%) are comparable to the clinical trial population. Follow-up is ongoing and updated data will be presented.
ABSTRACT
Background: The risk of severe COVID-19 is increased in patients (pts) with hematologic malignancies, with a reported risk of death of 34% (Vijenthira et al, 2020). The ASH-ASTCT COVID-19 vaccine guidelines indicate that certain immunocompromised patient populations could have an attenuated response to the SARS-CoV-2 vaccine. However, most SARS-CoV-2 vaccine trials required pts to be off immune suppression to be eligible and therefore excluded most pts with hematologic malignancies. Little is known about the efficacy of SARS-CoV-2 vaccines in pts with hematologic malignancies. In this study, we aimed to evaluate the serological response of Pfizer and Moderna vaccination after two doses given in pts with hematologic malignancies with a focus on pts with myeloid malignancies. Methods: Patients with a history of hematologic malignancies treated at the University of Texas Southwestern Medical Center and received two doses of vaccination with quantitative measurement of SARS-CoV-2 IgG Spike antibody to assess vaccination response were included in this study. Baseline patient and disease characteristics including disease status and therapy given at the time of vaccination were collected. Time to vaccine response was defined as having a positive quantifiable spike IgG antibody titer per the lab reference range. The development of COVID-19 infection as well as antibody titer levels were collected. Categorical variables were compared using Chi-square and Fisher's exact tests and student t-test and ANOVA test were used to compare continuous variables. Results: A total of 61 pts with hematologic malignancies had spike IgG antibody testing after receiving 2 doses of the vaccine were included in this study. The median age at the time of vaccination was 72 (22-85) and 46% of pts were female. Eighty five percent of pts were Caucasian. The majority of pts (67.3%) had a myeloid malignancy (MDS/CMML 29.5%, AML 14.8%, myelofibrosis 16.4%, CML 6.6%), followed by chronic lymphocytic leukemia (16.4%), and others (6.6%). The median time from hematologic malignancy diagnosis to the first vaccine dose was 51 months (0.4-337 months). At the time of vaccine administration, 46 (75%) of pts were on active therapy and 39 (64%) of pts had active disease. Median time from the second vaccine dose to IgG spike antibody testing was 64 days (26-268 days). Most pts (75%) mounted a serological response with quantifiable COVID-IgG spike antibodies, 85% and 56% in myeloid and lymphoid malignancy, respectively. All pts with MDS/CMML/CCUS and CML mounted an immune response (100%), followed by acute myeloid leukemia (n: 7/9, 78%) and myelofibrosis (n: 6/10, 60%). Eight (13%) of pts were receiving hypomethylating agent therapy at the time of vaccination and all (100%) had a positive IgG response. Only one patient developed COVID-19 infection post vaccination with a documented IgG response and 2 pts had COVID-19 infection prior to the first dose of vaccination, both of these pts had IgG titers >10,000. Sixty percent of pts (9/15) with negative IgG response received treatment with either CD20 monoclonal antibodies or BTK inhibitors within 12 months of the first vaccine dose. Two out of three pts (67%) receiving Ruxolitinib had negative serology. Seven pts were on treatment with hydroxyurea, interestingly, all but the 2 pts with polycythemia vera had a negative antibody titer while on treatment with hydroxyurea. There was a strong positive correlation between vaccine titer and absolute lymphocyte count (r 2=0.27, p<0.001) (Figure). Conclusions: In this retrospective study, we demonstrate a higher rate of COVID-19 vaccine efficacy in pts with myeloid malignancy with varying responses per treatment and disease subtype compared to pts with B-cell malignancy with variable anti-CD20 or BTK inhibitor therapy. Pts with myelodysplastic syndromes, overlap syndromes of clonal cytopenia of undetermined significance all developed spike antibodies irrespective of hypomethylating therapy or Hydrea as did pts with chronic myeloid leukemia. However, pts with polycythemia vera nd those on treatment with Ruxolitinib had an attenuated response to the vaccine. Albeit this single center study, pts with myelodysplastic syndromes should be offered COVID vaccines irrespective of their blood counts or ongoing treatment. Our findings should be validated in a larger group of patients. [Formula presented] Disclosures: Patel: Agios: Membership on an entity's Board of Directors or advisory committees;Celgene-BMS: Membership on an entity's Board of Directors or advisory committees;PVI: Honoraria. Anderson: Celgene, BMS, Janssen, GSK, Karyopharm, Oncopeptides, Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Awan: Cardinal Health: Consultancy;BMS: Consultancy;Dava Oncology: Consultancy;Karyopharm: Consultancy;Merck: Consultancy;Johnson and Johnson: Consultancy;Incyte: Consultancy;Beigene: Consultancy;Verastem: Consultancy;MEI Pharma: Consultancy;Celgene: Consultancy;Kite pharma: Consultancy;Gilead sciences: Consultancy;Pharmacyclics: Consultancy;Janssen: Consultancy;Abbvie: Consultancy;ADCT therapeutics: Consultancy;Astrazeneca: Consultancy;Genentech: Consultancy. Madanat: Blue Print Pharmaceutical: Honoraria;Onc Live: Honoraria;Stem line pharmaceutical: Honoraria;Geron Pharmaceutical: Consultancy.