Immunogenicity of Covid-19 Vaccine Among Multiple Myeloma Patients Post Autologous Stem Cell Transplant

Background:

mRNA vaccines against SARS-CoV-2 have proven to be safe and effective and have been widely administered. Multiple myeloma (MM) is a disease of plasma cells and is known to weaken the host immunity leading to ineffective vaccine response there by increasing the risk of contracting severe disease. Anti-MM therapy can further suppress the immune system and consequently worsen vaccine response. Autologous stem cell transplant (ASCT) is the standard of care for fit MM patients and leads to prolonged immunosuppression. The effect of ASCT on vaccine response has not been well studied. In an effort to elucidate optimal timing and number of vaccines post ASCT we investigated the seroconversion rate among MM patients who received at least one vaccination post ASCT

Methods:

We conducted a single center retrospective analysis in patients at the University of Arkansas Medical Center (UAMS) who underwent ASCT for MM and subsequently received at least one dose of either available mRNA vaccine (Pfizer or Moderna). Antibody titers against SARS-CoV-2 spike glycoprotein were checked at various timelines post vaccination. Testing was performed using Roche Elecsys Anti SARS CoV-2 reagent assay from Roche diagnostics. We categorized the patients into two groups: complete responders with titers levels more than 250 U/ml and partial responders/non-responders with titers levels less than 250 U/ml. Covariates used were age, sex, race, MM isotypes, vaccine count, time from last transplant to first dose of vaccine and maintenance therapy post ASCT. Welch's t-test and Wilcoxon rank-sum test were used for continuous variables, while Fisher's exact test was used for categorical variables.

Results:

A total of 64 patients were analyzed. The mean age was 62.5 years (Range:35-81), with 39.1% (25/69) being female. The most common isotype was IgG and the most common free light chain was kappa, comprising 73.1% (38/53) and 68.8% (44/64) respectively. All patients initiated maintenance after ASCT consisting of daratumumab (30/64, 47.6%), proteosome inhibitors (47/64, 74.6%), immunomodulators (50/64, 78.7%) and steroids (58/64, 92.1%). The first vaccine dose was given at a minimum of 70 days after ASCT and for vaccinations that were given during the maintenance period, treatments were held one week prior and after each vaccine dose. The median follow up duration in days from 1st transplant to last follow-up was [Median, Inter quartile range (IQR)]: 152.0 (68.8, 254.3). At time point of data collection 25/64 (39.1%) had received at least 3 vaccines prior to titer assessment. Of those, 18/25 (72%) were complete responders compared to 7/25 (18%) partial/non-responders, p=0.02. In total, we observed 53.1% of subjects in the entire cohort mounted a complete response (>250 U/ml). Within the complete responders, there were significantly more patients who had received at least 3 vaccines post ASCT having higher chances of a complete response compared to those who received less vaccines, regardless of how many vaccines were given prior to ASCT, 76.5% vs 23.5%, p=0.03. There was a trend towards more time from transplant to first vaccine being associated with a complete antibody response (median days of 171 for complete responders vs 128 days for non/partial responders), albeit that was not significant, p=0.3. Factors that adversely impacted antibody response were higher age (>65), p=0.02 and daratumumab containing maintenance, p=0.04. Intriguingly, we observed significantly better antibody response in patients with IgA MM isotype compared to IgG Isotype, p=0.03, albeit the numbers were small for this analysis (IgA n=14/65). No significant difference was noted between complete and partial/non responders in regard to sex, race, light chain type, IVIG administration and other maintenance regimens. At the time point of data collection, a total of three patients developed symptomatic Covid infections, all of which were in the non-responders/partial responders' group; none of them required hospitalization.

Conclusion:

The administration of at least 3 mRNA Covid vaccines post ASCT leads to significantly improved antibody titers and should be the minimum standard in this patient population. Higher age (>65 years), IgG subtype and daratumumab based maintenance were associated with suboptimal response to Covid vaccine among post ASCT and those MM patients should have high priority to receive additional prophylactic measures.

van Rhee:Janssen Pharmaceuticals: Research Funding; Takeda: Consultancy; Karyopharm: Consultancy; GlaxoSmithKline: Consultancy; EUSA Pharma: Consultancy; Bristol Myers Squibb: Research Funding. Schinke:Janssen: Honoraria.