COVID-19 Humoral Immunity Improves with Third and Subsequent Vaccine Doses in Patients with Plasma Cell Dyscrasias, Particularly in Those Receiving antiCD38 Therapy
Authors: Bhella Sita D. , Wilkin Allison M. , Hueniken Katrina , Vijenthira Abi , Sebag Michael , Wang Peng , Hicks Lisa K , Hay Annette E. , McCurdy Arleigh , Hosseini-Moghaddam Seyed , Reece Donna , Assouline Sarit E. , Fraser Graeme Andrew McCrae , Balitsky Amaris K , Mangel Joy , Owen Carolyn , Reiman Anthony , Sehn Laurie H. , Sutherland Heather J. , Arnold Corey , Leite Tamara , McCarthy Erinn , Cooper Curtis , Langlois Marc-Andre , Buchan C. Arianne 
Published: December 2024

Background
Immune response to COVID-19 vaccine is diminished in patients (pts) with plasma cell dyscrasias (PCD). An emphasis has been placed on completing repeated doses of vaccine in this population but limited data regarding response to serial vaccine dosing exist.
Purpose
To quantify the humoral immune response engendered by 3rd and subsequent doses of SARS-CoV-2 vaccination as measured by anti-Spike (anti-S) antibody levels, based on dried blood spot (DBS) testing, in pts with PCD.
Methods
We conducted a prospective study of pts with hematologic malignancies between August 2021 and January 2023 at 12 Canadian sites. Participants were followed longitudinally and submitted finger-prick DBS cards at set intervals associated with vaccination. Samples were processed via high throughput ELISA assay to detect serum antibodies against nucleocapsid (N) and spike (S) proteins. We explored seroresponse from anti-S- to anti-S+ with subsequent vaccine dosing through paired DBS samples pre- and post-dose 3,4,5. Pre-dose samples were taken &lt;60 days before vaccination and post dose samples were taken 7-42 days after vaccination.
Results
Out of this cohort's 791 pts with hematologic malignancies, we obtained 1033 samples from 277 pts with PCD [median age was 65 years, 53% female]. Sixty-nine pts (26%) underwent autologous stem cell transplant (ASCT), 6 (2%) received immune effector cell therapy. 259,260, 186, 75 and 15 pts received 2,3,4,5 and 6 vaccine doses respectively. At study initiation, 5.6% (95% CI 2.9, 8.3) were anti-N positive, increasing to 21.1% (95% CI 14.6, 27.5) at study end. 67.3% (95% CI 58.6, 76.0) were anti-S positive at study initiation increasing to 93.6% (95% CI 90.2, 96.9) at study end.
The percentage of pts with an anti-S+ at one month after 3rd dose was 83.7% (95% CI 77.5,90.0), which decreased to 70.6% (95% CI 62.9,78.4) at six months. Similarly, anti-S+ seroresponse after the 4th dose decreased from 85.8% (95% CI 80.1,91.4) at one month to 82.5% (95% CI 74.4, 90.6) at six months.
We analyzed paired samples from pts who submitted DBS samples pre- and post-vaccine doses. For dose 3, 6/23 (26.1%) of pts with a negative anti-S pre-dose converted to positive anti-S after receipt of the 3rd dose. For dose 4, 7/75 (9.4%) converted from a negative anti-S pre-dose to a positive result post-dose. Although 20 paired samples were available for analysis pre-post dose 5, no pt was anti-S negative before the dose.
Anti-S+ seroresponse was explored post dose 3,4, and 5 by current type of myeloma therapy. Pts were categorized as receiving anti-CD38 mAb (antiCD38) versus no anti-CD38 mAb (no mAb) treatment. 78 pts had DBS samples post dose 3, 14 antiCD38, 64 no mAb. Post dose 3, 87%,50% and 95% of the whole cohort, antiCD38 and no mAb respectively were anti-S +. 117 pts had DBS samples post dose 4, 41 antiCD38, 76 no mAb. Post dose 4, 86%,68% and 96% of the whole cohort, antiCD38 and no mAb cohorts were anti-S + respectively. 58 pts had DBS samples post dose 5, 16 antiCD38, 42 no mAb. Of the full cohort post dose 5, antiCD38 and no mAb, 97%,100% and 95% were anti-S + respectively.
We analyzed paired samples from pts who submitted DBS samples pre-and post-vaccine and explored by treatment group. 20 paired samples among no mAb pts were available pre-post dose 3 and 6/20 pts had a seroresponse from anti-S - to anti-S+. No seroconversion was noted pre-post dose 3 among 2 paired anti-S- samples in the antiCD38 group.
27 paired samples were in the antiCD38 group pre-post dose 4 and there was seroresponse of 2/27 pts and no seroresponse of the 10/27 remaining anti-S-pts post dose 4. In the no mAb group, 44 paired samples were available, 6/44 were anti-S negative and 4/6 (66.7%) demonstrated seroresponse post dose 4.
Of 277 pts, we examined the presence of COVID-19 infection by follow up questionnaire and chart review. 70/243 (29%) self-reported a COVID-19 infection. 48/189 (25%) and 4/189(2%) were noted to have a COVID-19 infection and hospital admission on chart review respectively. There were no recorded deaths from COVID-19.
Conclusion
This prospective cohort study demonstrated that humoral immune response improved with subsequent doses of COVID-19 vaccines for PCD pts. Pts receiving antiCD38 therapy had lower proportions of anti-S positivity, which improved with subsequent vaccines. Seroresponse to subsequent vaccinations were noted with conversion to anti-S +. Low hospitalization and mortality rate in this at-risk population is noteworthy.