ABSTRACT
Background: Coronavirus-2 has profound effects on patients (pts) with Multiple myeloma (MM). At the beginning of the pandemic, COVID-19 infection resulted an overall mortality around 54% (cook et al. BMJ 2020). Here, we report an updated morbidity and fatality for MM. Methods: After obtaining IRB approvals from each participating institute, retrospectively, between January 1, 2021 and August 30, 2021, we identified pts with MM and COVID-19 in two myeloma centers (Levine Cancer Institute (LCI) & the University of Kansas medical center (KUMC). Results: We identified 162 MM pts who had COVID- 19 (LCI n=132, UKMC n=30), including 57% males, with median age of 64 years. Current or former smoking reported in 40% of pts. Most pts have associated comorbid conditions: hypertension (45%), hypogammaglobulinemia (32%), CKD (30%), DM (22%), obesity (16.6%), CHF (14%), and CAD (13.5%). Within 3 months prior to infection, treatment included immunomodulatory combinations in 35%, proteasome inhibitors in 28 %, and Daratumumab in 26.5%. Symptoms are summarized in table. 69% had Mild symptoms (no need for hospitalization), 20 % had moderate symptoms (requiring hospitalization), and 9.8% had severe symptoms (ICU level of care). The 18% of pts required oxygen: 6 pts required invasive oxygenation and 3 pts needed vasopressors. The 32% of pts had RRMM, 29.5% on maintenance, and 12% was getting induction. Regarding MM response: >VGPR in 45% and PD in 18%. The 78 pts had ASCT prior to COVID-19 infection: only 3 pts < 1 year and 3 pts < 6 months. MM response or ASCT did not affect hospitalization or mortality.The case fatality rate (CFR) was 6%. In the univariate analysis, CKD, DM, HTN and hepatic dysfunction were associated with an increased risk of hospitalization. However, in multivariate analysis, only CKD, hepatic dysfunction, and Hypogammaglobulinemia significantly increased the risk of admission with only age and lymphopenia were associated with increased COVID-19 related fatatlity. Conclusions: With implementation of center-specific disease control measures and universal screening, pts might have lower case severity and fatality rate than was initially reported.
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 Patients (Pts) with multiple myeloma (MM) experience prolonged immunosuppression due to the incurable nature of the disease and corresponding treatment modalities. Due to this many MM pts with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) require hospitalization, with an increased mortality rate over healthy adults. Two mRNA vaccines against (SARS-CoV-2): BNT162b2 & mRNA-1273 were approved under an emergency use authorization (EUA) by the Food and Drug Administration (FDA) due to the high efficacy in preventing SARS-CoV-2. The aim of this study was to analyze the antibody (Abs) response in all pts with plasma cell disorders (PCD) including MM, AL-Amyloidosis, and smoldering myeloma (SMM) who are on active treatment. Patients & Methods All pts (MM, AL-Amyloidosis, and SMM) on active treatment who received SARS-CoV-2 mRNA vaccine were identified at the University of Kansas Health System between January 2021 to July 2021and reviewed retrospectively. Descriptive analyses were performed on available data for patient characteristics. Abs against SARS-CoV-2 were measured using methodology approved by the FDA (enzyme-linked immunosorbent assay;cPass SARS-CoV-2 Neutralizing Antibody Detection Kit;GenScript, Piscataway, NJ). We stratified pts into clinically relevant responders (>250 IU/mL), partial responders (50-250 IU/mL), and non-responders (<50 IU/mL) Results A total of 118 pts were identified in our analysis and are described in Table 1. Of the total pts, 102 (86%) had MM, 13 (11%) pts had AL-Amyloidosis, and 3 (3%) pts had SMM. Median age was 69 years (45-95), 96 pts (81%) were Caucasian, and 57 (48%) were male. Median lines of prior treatment was 2 (1-13). Active PCD patients were treated with single-agent therapy in 60 pts (51%), doublet-based therapy in 5 pts (4%), and triplet-based therapy in 51 pts (43%). Daratumumab based therapy was utilized in 59 pts (50%). All pts included received two doses of either BNT162b2 or mRNA-1273. At the time of abs testing 82 patients (69%) were in a very good partial response (VGPR) or better, 29 pts (25%) were in partial response, while 7 pts (6%) had stable disease. Five pts (4%) had COVID-19 infection prior to the vaccine. The median time between thesecond dose of the vaccine and testing for Abs was 100 days (34-190). Only 46 pts (39%) developed an adequate response, 36 pts (30.5%) had a partial response, while 36 (30.5%) did not respond to the vaccine. Low Ab levels were seen in all PCD subtypes with the following mean levels: SMM :25.4 (5.4- 36.9) IU/mL, MM 148 (0- >250) IU/mL, and AL- Amyloidosis 92.35 (range 0- >250) IU/mL. Among the 5 pts with COVID-19 infection prior to the vaccination, full Abs response was observed in 4 pts, and 1 patient had no Abs response. Type of treatment did not affect the response to treatment in any clinically meaningful way. The odds ratio of achieving a clinically relevant Abs response was higher in pts with absolute lymphocyte counts>0.5 K/uL (p=0.01) and IgG levels> 400 mg/dL (p=0.04) and lower in pts receiving treatments with daratumumab combinations or anti-BCMA therapy (p<0.0001). Higher levels of anti-SARS-CoV-2 Abs were observed in pts with ≥ VGPR (mean≈147 IU/mL) compared to <VGPR (mean≈ 119 IU/mL). However, in this dataset, this difference was not statistically significant (p=0.17). Conclusion mRNA vaccine Ab response is lower in PCD pts getting active treatment compared with the general population. For PCD patients on active treatment, mRNA vaccine produced full antibody responses and partial responses in 39% and 30.5% of pts, respectively. anti-SARS-CoV-2 abs are especially low for patients on daratumumab combinations or anti-BCMA therapy, low lymphocytes, and low IgG levels at the time of vaccination. Some PCD may not develop anti-SARS-CoV-2 abs despite vaccination and/or previous COVID-19 infection. Therefore, checking anti-SARS-CoV-2 abs may be clinically useful in identifying patient's response. Further prospective studies should ascertain the value of a 3 rd vaccine dose in this population. [Fo mula presented] Disclosures: Mahmoudjafari: Omeros: Membership on an entity's Board of Directors or advisory committees;GSK: Membership on an entity's Board of Directors or advisory committees;Incyte: Membership on an entity's Board of Directors or advisory committees. McGuirk: Astelllas Pharma: Research Funding;Juno Therapeutics: Consultancy, Honoraria, Research Funding;EcoR1 Capital: Consultancy;Gamida Cell: Research Funding;Magenta Therapeutics: Consultancy, Honoraria, Research Funding;Fresenius Biotech: Research Funding;Bellicum Pharmaceuticals: Research Funding;Novartis: Research Funding;Pluristem Therapeutics: Research Funding;Allovir: Consultancy, Honoraria, Research Funding;Kite/ Gilead: Consultancy, Honoraria, Other: travel accommodations, expense, Kite a Gilead company, Research Funding, Speakers Bureau;Novartis: Research Funding. Atrash: Jansen: Research Funding, Speakers Bureau;AMGEN: Research Funding;GSK: Research Funding.