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286 COVID-19 Humoral Immunity Improves with Third and Subsequent Vaccine Doses in Patients with Plasma Cell Dyscrasias, Particularly in Those Receiving antiCD38 Therapy

Program: Oral and Poster Abstracts
Type: Oral
Session: 907. Outcomes Research: Plasma Cell Disorders: Quality Matters and Key Outcomes in Multiple Myeloma
Hematology Disease Topics & Pathways:
Clinical Practice (Health Services and Quality), Plasma Cell Disorders, Diseases, SARS-CoV-2/COVID-19, Infectious Diseases, Lymphoid Malignancies
Saturday, December 7, 2024: 2:45 PM

Sita D. Bhella, MD1, Allison M. Wilkin, PhD2*, Katrina Hueniken3*, Abi Vijenthira, MD, SM4, Michael Sebag, MD, PhD5, Peng Wang, MD, PhD6*, Lisa K Hicks, MD7, Annette E. Hay, MD, FRCPath, FRCPC8, Arleigh McCurdy, MD9, Seyed Hosseini-Moghaddam10*, Donna Reece, MD1, Sarit E. Assouline, MD11, Graeme Andrew McCrae Fraser, MD, MSc, FRCPC12, Amaris K Balitsky, MD, MSc, FRCPC13, Joy Mangel, MD, FRCPC14, Carolyn Owen, MD, FRCPC15, Anthony Reiman, MD16, Laurie H. H. Sehn, MD17, Heather J. Sutherland, MD, PhD, FRCPC18, Corey Arnold19*, Tamara Leite20*, Erinn McCarthy21*, Curtis Cooper22*, Marc-Andre Langlois23* and C. Arianne Buchan24*

1Princess Margaret Cancer Centre, Toronto, ON, Canada
2Ottawa Health Research Institute, Ottawa, ON, Canada
3Department of Biostatistics, University Health Network, Toronto, ON, Canada
4Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada
5McGill University, Montréal, QC, Canada
6Department of Medicine, University of Alberta, Edmonton, AB, Canada
7Division of Hematology/Oncology, St. Michael's Hospital, Toronto, ON, Canada
8Division of Hematology, Department of Medicine, Queen's University, Kingston, ON, Canada
9The Ottawa Hospital, Ottawa, ON, Canada
10University Health Network/Toronto General Hospital, Toronto, ON, CAN
11Jewish General Hospital, McGill University, Westmount, QC, Canada
12Department of Oncology, McMaster University, Hamilton, ON, Canada
13Juravinski Cancer Centre, Department of Oncology, McMaster University, Hamilton, Canada
14Department of Medicine, Division of Hematology, University of Western Ontario, London, ON, Canada
15Tom Baker Cancer Centre, Alberta Health Services, Calgary, AB, Canada
16Department of Oncology, Saint John Regional Hospital, Saint John, NB, Canada
17Division of Medical Oncology, University of British Columbia, Vancouver, BC, Canada
18Vancouver General Hospital, Vancouver, BC, Canada
19Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada
20The Ottawa Hospital Research Institute (OHRI), Ottawa, Canada
21Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada
22Ottawa Hospital Research Institute, Ottawa, ON, Canada
23University of Ottawa, Ottawa, ON, CAN
24The University of Ottawa, Ottawa, Canada

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 <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.

Disclosures: Bhella: Kite/Gilead: Consultancy, Honoraria. Sebag: GSK: Honoraria; Takeda: Honoraria; Karyopharm: Honoraria; Janssen: Honoraria, Research Funding; Sanofi: Honoraria; BMS: Honoraria; Amgen: Honoraria. Hay: Merck, Seattle Genetics, Janssen, Incite, Roche, AbbVie, Karyopharm: Research Funding. Reece: Janssen, BMS, Sanofi, ORIC, Princess Margaret Cancer Centre: Other: Grants; BMS, Janssen, Sanofi, GSK, Pfizer: Consultancy; BMS, Janssen, Takeda, Pfizer: Honoraria; BMS: Membership on an entity's Board of Directors or advisory committees. Assouline: AstraZeneca: Consultancy, Honoraria; Novartis Canada Inc.: Research Funding; BeiGene: Consultancy, Honoraria; Genentech/Roche: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; F. Hoffman-La Roche Ltd.: Consultancy, Honoraria; Ipsen: Consultancy; Gilead: Honoraria; Pfizer: Consultancy. Balitsky: Sobi: Consultancy; BMS: Consultancy; Novartis: Research Funding; Beigene: Honoraria; Kite/Gilead: Honoraria. Owen: Janssen, Roche, Merck, Gilead, Servier, Seattle Genetics, Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie, AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaker; Beigene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Sehn: Teva: Other: Research Grants; Roche, Seattle Genetics: Speakers Bureau; AbbVie, Acerta, Apobiologix, AstraZeneca, Celgene, Debiopharm, Genentech, Genmab, Gilead Sciences, Incyte Corporation, Janssen, Karyopharm Therapeutics, Kite Pharma, Lundbeck, Merck, MorphoSys, Novartis, Sandoz, Takeda, TG Therapeutics, Verastem Oncology: Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd; Genentech, Inc.; Teva: Research Funding; AbbVie; Amgen; AstraZeneca; Beigene; BMS/Celgene; Genmab; Kite/Gilead; Incyte; Janssen; Merck; Seagen; F. Hoffmann-La Roche Ltd; Genentech, Inc.: Honoraria; AbbVie; Amgen; AstraZeneca; Beigene; BMS/Celgene; Genmab; Kite/Gilead; Incyte; Janssen; Merck; Seagen; F. Hoffmann-La Roche Ltd; Genentech, Inc.: Consultancy. Sutherland: GSK: Research Funding; Sanofi: Consultancy; Karyopharm: Research Funding; Amgen: Consultancy; Celgene: Consultancy; Janssen: Consultancy, Research Funding.

*signifies non-member of ASH