ABSTRACT
[Formula presented] Introduction: Recent data suggest a suboptimal antibody response to COVID-19 vaccination in patients with hematological malignancies. Herein, we evaluated the development of neutralizing antibodies (NAbs) against SARS-CoV-2 in patients with plasma cell neoplasms (PCNs) after vaccination with either the mRNA BNT162b2 or viral vector AZD1222 vaccine, up to 50 days post their first vaccine dose. Methods: This is an ongoing large prospective study (NCT04743388) evaluating the kinetics of anti-SARS-CoV-2 antibodies after COVID-19 vaccination in healthy subjects and in patients with hematological malignancies or solid tumors. Here we present the data on patients with PCNs in comparison to controls of similar age and gender, who were vaccinated during the same time period (January to March 2021) in Athens (Greece). Major exclusion criteria for both patients and controls included the presence of: (i) autoimmune disorder under immunosuppressive therapy or other active malignant disease;(ii) HIV or active hepatitis B and C infection, (iii) end-stage renal disease and (iv) prior diagnosis of COVID-19. Serum was collected on day 1 (D1;before the first vaccine dose), on day 22 (D22;before the second dose of the BNT162b2 or 3 weeks post the first AZD1222 dose) and on day 50 (D50;4 weeks post second dose of the BNT162b2 or 7 weeks post the first AZD1222 dose). NAbs against SARS-CoV-2 were measured using an FDA approved-ELISA methodology (cPass™ SARS-CoV-2 NAbs Detection Kit, GenScript, Piscataway, NJ, USA). Results: We evaluated 382 patients with PCNs after vaccination with either the BNT162b2 or the AZD1222 vaccine. Patients with MM (n=213), WM (n=106), SMM (n=38) and MGUS (n=25) and 226 healthy controls were enrolled in the study. Of MM/SMM/MGUS patients, 215 (77.9%) were vaccinated with the BNT162b2 and 61 (22.1%) with the AZD1222 vaccine, while out of 106 WM patients 90 (84.9%) were vaccinated with the BNT162b2 and 16 (15.1%) with the AZD1222 vaccine. Vaccination with either two doses of the BNT162b2 or one dose of the AZD1222 vaccine led to lower production of NAbs against SARS-CoV-2 in patients compared with controls both on day 22 and on day 50 (P<0.001 for all comparisons). After the first dose of the vaccine, on D22, the patient group had lower NAb titers compared with controls: the median NAb inhibition titer was 27% (IQR: 15.3-42%) for MM/SMM/MGUS versus 20.5% (IQR: 10-37%) for WM patients versus 38.7% (IQR: 22-54.3%) for controls (P<0.001 for all comparisons). On D50 the median NAb inhibition titer was 62.8% (IQR: 26-88.9%) for MM/SMM/MGUS versus 36% (IQR: 18-78%) for WM patients versus 90% (IQR: 58-96.4%) for controls (P<0.001 for all comparisons). 57.3% MM/SMM/MGUS, 42% WM patients and 81% controls developed NAb titers ≥50% (p<0.001 for patients versus controls). Furthermore, MM patients showed an inferior NAb response compared with MGUS on day 22 (p=0.009) and on day 50 (p=0.003). Importantly, active treatment with either anti-CD38 monoclonal antibodies or belantamab mafodotin and lymphopenia at the time of vaccination were independent prognostic factors for suboptimal antibody response following vaccination in MM (p<0.05). Disease-related immune dysregulation and therapy-related immunosuppression were involved in the low humoral response in patients with WM. Importantly, active treatment with either rituximab or Bruton's Tyrosine Kinase inhibitors (BTKIs) was proven as an independent prognostic factor for suboptimal antibody response following vaccination in WM (p<0.05). Regarding adverse events, 33% and 31.6% patients reported mild reactions after the first and second dose of the BNT162b2 vaccine, respectively;32.8% patients vaccinated with the first dose of AZD1222 also presented with local reactions. Conclusion: Patients with MM and WM have a low humoral response following SARS-CoV-2 vaccination, especially those who are under treatment with anti-CD38-, anti-BCMA-, anti-CD20- or BTKIs-based regimens. This result suggest that these patients have to continue the protective measures ag inst SARS-CoV-2 as they are at high risk for COVID-19. Further studies on the kinetics of immune subpopulations following COVID-19 vaccination will elucidate the underlying immune landscape and determine the potential need for additional booster vaccine doses or protective administration of antibodies against SARS-CoV-2 in MM/WM patients with poor response after full vaccination. Disclosures: Terpos: Janssen-Cilag: Consultancy, Honoraria, Research Funding;BMS: Honoraria;Celgene: Consultancy, Honoraria, Research Funding;Genesis: Consultancy, Honoraria, Research Funding;GSK: Honoraria, Research Funding;Takeda: Consultancy, Honoraria, Research Funding;Sanofi: Consultancy, Honoraria, Research Funding;Novartis: Honoraria;Amgen: Consultancy, Honoraria, Research Funding. Gavriatopoulou: Janssen: Honoraria;Takeda: Honoraria;Sanofi: Honoraria;Karyopharm: Honoraria;Genesis: Honoraria;GSK: Honoraria;Amgen: Honoraria. Kastritis: Amgen: Honoraria, Research Funding;Janssen: Honoraria, Research Funding;Genesis: Honoraria;Takeda: Honoraria;Pfizer: Honoraria. Dimopoulos: Janssen: Honoraria;BeiGene: Honoraria;Takeda: Honoraria;Amgen: Honoraria;BMS: Honoraria.
ABSTRACT
Introduction: Recent data suggest a suboptimal antibody response to COVID-19 vaccination in patients with multiple myeloma (MM), especially under treatment. Herein, we evaluated the development of neutralizing antibodies (NAbs) against SARS-CoV-2 in non-vaccinated MM patients who were diagnosed with COVID-19 compared to MM patients after full vaccination with the mRNA BNT162b2 vaccine. Methods: The analysis was performed in the context of an ongoing large prospective study (NCT04743388) evaluating the kinetics of anti-SARS-CoV-2 antibodies after COVID-19 vaccination. We evaluated MM patients diagnosed with COVID-19, confirmed by PCR, matched for age, gender, line of treatment, type of myeloma, type of treatment and response with vaccinated MM patients during the same time period (January - May 2021). Major exclusion criteria for both COVID-19 and vaccine MM groups included the presence of: (i) autoimmune disorder under immunosuppressive therapy or other active cancer;(ii) active HIV, hepatitis B and C infection, and (iii) end-stage renal disease. Serum was collected at 4 th week post confirmed diagnosis for the COVID-19 MM group and at 4 th week post the second BNT162b2 dose for the vaccine MM group. NAbs against SARS-CoV-2 were measured using an FDA approved methodology (cPass™ SARS-CoV-2 NAbs Detection Kit, GenScript, Piscataway, NJ, USA). Results: We evaluated 35 patients with MM and COVID-19 (6 had smoldering MM and 29 symptomatic MM), along with 35 matched MM patients who received the BNT162b2 vaccine. Among COVID-19 MM patients, 13 were diagnosed with mild, 12 with moderate and 10 with severe disease;22/35 patients were hospitalized and 10/35 were intubated. Seven (20%) patients died due to COVID-19. During the disease course 21 patients (60%) were treated with dexamethasone. Type of treatment was not different between COVID-19 positive and vaccinated MM patients. Between the two patient groups, there was no difference in terms of age [median (IQR) 65 (59) for COVID-19 positive versus 66 (74) for COVID-19 vaccinated, respectively, p=0.76], gender [males: 19/35 (54.3%) versus 16/35 (45.7%), respectively, p=0.47), BMI (median 27 versus 26kg/m 2, respectively, p=0.56), asymptomatic disease [6/35 (18.2%) in both groups, p=1], prior lines of treatment [range: 1 to 7 versus 1 to 6, respectively, p=0.99], and type of treatment (p=0.87). Among the COVID-19 MM patients, 6 (20.7%) were in sCR/CR, 6 (20.7%) in VGPR, 12 (41.4%) patients in PR, 2 (6.9%) in MR/SD and one (3.5%) in PD at the time of confirmed infection. Among the vaccinated MM group, 10 (34.5%) patientswere in sCR/CR, 4 (13.8%) in VGPR, 11 (37.9%) in PR, one (3.5%) in MR/SD and one (3.5%) in PD at the time of vaccination (p-value=0.93 for the comparison between COVID-19 and vaccinated MM groups). No differences between COVID-19 and vaccinated MM patients were also noted regarding the median lymphocyte count (1200/μl versus 1400/μl, respectively, p=0.08) and the median immunoglobulin values (IgG 732 mg/dl versus 747 mg/dl, respectively, p=0.29;IgA 9 mg/dl versus 61 mg/dl, respectively, p=0.7;IgM 26 mg/dl versus 25 mg/dl, p=0.97). The incidence of comorbidities was also similar between the two groups (cardiovascular diseases 55.2% versus 44.8%, respectively, p=0.47;diabetes mellitus 66.7% versus 33.3%, p=0.28;chronic pulmonary disease 50% each, p=1.0). Interestingly, patients with MM and COVID-19 showed a superior humoral response compared with vaccinated MM patients. The median (IQR) NAb titers were 87.6% (IQR: 71.6-94) and 58.7% (21.4-91.8) for COVID-19 and for vaccinated MM patients, respectively (p=0.01). In both groups, 27 out of 35 patients were receiving active treatment for MM at the time of NAb evaluation. The median NAb titer was 88% (IQR 71.6%-96.3%) for COVID-19 MM patients and 35.4% (IQR 17.5%-85.5%) for vaccinated MM patients who received anti-myeloma therapy (p=0.001). Importantly, there was no difference in NAb production between COVID-19 and vaccinated MM patients who did not receive any treatment (median NAb titers, 85.1% versus 91 7%, p=0.14). Conclusion: Patients with MM and COVID-19 present a superior NAb response against SARS-CoV-2 compared with fully vaccinated patients with the BNT162b2 vaccine. This finding was more pronounced among patients receiving active treatment for MM. In this context, additional booster doses may be considered for MM patients with poor humoral response after the BNT162b2 vaccine. [Formula presented] Disclosures: Gavriatopoulou: Genesis: Honoraria;Karyopharm: Honoraria;Takeda: Honoraria;Janssen: Honoraria;Sanofi: Honoraria;GSK: Honoraria;Amgen: Honoraria. Terpos: BMS: Honoraria;Celgene: Consultancy, Honoraria, Research Funding;Sanofi: Consultancy, Honoraria, Research Funding;Takeda: Consultancy, Honoraria, Research Funding;Janssen-Cilag: Consultancy, Honoraria, Research Funding;GSK: Honoraria, Research Funding;Novartis: Honoraria;Genesis: Consultancy, Honoraria, Research Funding;Amgen: Consultancy, Honoraria, Research Funding. Kastritis: Amgen: Consultancy, Honoraria, Research Funding;Genesis Pharma: Honoraria;Janssen: Consultancy, Honoraria, Research Funding;Pfizer: Consultancy, Honoraria, Research Funding;Takeda: Honoraria. Dimopoulos: Amgen: Honoraria;BMS: Honoraria;Janssen: Honoraria;Takeda: Honoraria;BeiGene: Honoraria.
ABSTRACT
Background: The SARS-CoV-2 pandemic has caused innumerable social and economic consequences, has stressed health care systems, affecting the delivery of health care and raising concerns that many patients may have suffered delays in therapy and in the diagnosis of serious conditions, such as hematologic and other malignancies. This effect may be more pronounced in older patients, who are at higher risk for COVID-19 complications, but which may also be affected by social isolation and distancing, difficulties in reaching health care facilities and fear of acquiring the infection. Myeloma patients are a vulnerable, mostly elderly population who may have been affected in terms of diagnosis and treatment delivery during the pandemic. There is a concern that diagnosis may be delayed, potentially presenting with more advanced disease or more often with severe complications. Aims: To provide evidence for the care of patients with myeloma, during the COVID-19 era, we compared the characteristics of newly diagnosed patients during 2020 and 2019 (i.e pre COVID-19 pandemic). Methods: We compared baseline characteristics and short-term outcomes of newly diagnosed MM patients who were diagnosed and started therapy in a tertiary referral center (Department of Clinical Therapeutics, Athens) during two calendar periods, 2019 and 2020. Initial restrictive measures were first implemented in Greece in mid-February 2020 and national lockdown in mid-March. Data were collected through our prospectively maintained database that includes all patients with a diagnosis of myeloma in our center. Since the beginning of the pandemic in Greece, our department implemented preventive measures and operating procedures to ensure continuous delivery of care and reduce the risk of COVID-19 infection. Results: In 2019,125 MM patients with a new diagnosis of symptomatic disease started therapy vs101 in 2020. The distribution of new cases per month was similar between the two years (p=0.542). Gender distribution was similar, but patients diagnosed in 2020 were slightly older (median 69 vs 66 years for 2019, p=0.084). There were no differences in baseline anemia, renal function, need for dialysis or ISS stage;however, slightly more patients had high risk cytogenetics in 2020 vs 2019 (37% vs 27%, p=0.129). The median time from the first test for the diagnosis to start of therapy was15 days in 2019 vs 8 days in 2020. First line therapies were similar with the majority receiving a PI plus IMiD combination (mostly VRD: 70% in 2019 vs 76% in 2020). Radiotherapy due to MM-related complications was required in 2.4% vs 4% of patients in 2019 and 2020 respectively. Early mortality (death <3 months from start of therapy) was 2.4% in 2019 and 5% in 2020 (p=0.314). The number of autologous transplants was slightly smaller in 2020 vs 2019 (54 vs 61). Infection rates during induction, which may have been affected by the use of social distancing and protective measures, was similar (15% vs16%);however, less patients required hospitalization for infection management in 2020 (in 8% vs16% in 2019). Very few cases of COVID-19 occurred among our MM patients and in only one newly diagnosed MM patient. Summary/Conclusion: Despite the pandemic, we did not observe significant delays or changes in the characteristics of patients that were diagnosed with myeloma between 2019 and 2020 in our center, neither in the short-term outcomes of our patients. Despite the pandemic it is possible to maintain delivery of high-quality specialized care in patients with myeloma.