Response to COVID-19 Vaccination Post-CAR T Therapy in Patients with Non-Hodgkin Lymphoma and Multiple Myeloma

ABSTRACT

Background:COVID-19 adversely affects individuals with cancer. Several studies have found that seroconversion rates among patients with hematologic malignancies are suboptimal when compared to patients without cancer. Among patients with hematologic malignancies, seroconversion rates also appear to be influenced by recent treatment and the type of treatment they have received. Patients with non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) are immunocompromised due to impaired humoral and cellular immunity in addition to prescribed immunosuppressive therapy. Chimeric antigen receptor T-cell (CAR T) therapy is now widely used for NHL and MM, but little is known about seroconversion rates after COVID-19 vaccination among these populations. Current national guidelines recommend COVID-19 vaccination to be offered to CAR T recipients as early as three months thereafter. We retrospectively evaluated SARS-CoV-2 spike-binding IgG antibody levels following COVID-19 vaccination among NHL and MM CAR T therapy recipients. Methods:This retrospective study was conducted at three Mayo Clinic sites on NHL and MM patients that received CAR T infusions from Sept 2016 to June 2021. Baseline characteristics were ascertained from medical records. All NHL and MM patients who had received CAR T at any point and were alive at the time that the COVID-19 vaccine first became available were eligible for inclusion for antibody response evaluation. For antibody response to vaccination, antibody spike values > 0.80 U/mL were considered positive. Results: Out of 104 CAR T infusions, 73 patients are alive at the time of this submission. We have had 7 patients with known COVID-19 pre-CAR T and all 7 are currently alive (5 have antibody titers and 2 have not been tested yet). Nineteen patients developed known COVID infection post-CAR T (13 alive and 6 deceased). The mortality of COVID post-CAR T in our sample was 31.5%. Furthermore, of the 13 patients that survived COVID-19, they received CAR T an average of 416 days prior to COVID-19 infection (median = 337, range = 54 - 1406);the 6 patients who died from COVID-19 had received CAR T an average of 250 days prior to COVID-19 infection (median = 164, range = 7 - 846). All 6 deceased patients did not receive COVID-19 vaccination pre-CAR T. Out of 17 CAR T patients tested for antibody spike titers post COVID-19 vaccination, 76.4% were able to mount an antibody response. More patients with MM had a higher titer response to the vaccine (>250 U/mL) compared to the NHL counterparts (0.80-249 U/mL). All patients that received the vaccine, regardless of antibody response, were alive at the time of this submission. Conclusions:The majority of CAR T recipients with NHL and MM are able to mount an antibody response following COVID-19 vaccination in our relatively small sample. The frequency of seroconversion among CAR T recipients seems to be similar to patients with hematologic malignancy who had received a hematopoietic cell transplant reported elsewhere. These findings are limited by our small sample size and may be influenced by the timing of vaccination relative to CAR T. Furthermore, almost half of our patients received IVIG post CAR T which could potentially cause false positive antibody results as pooled immunoglobulin preparations may contain COVID-19 antibodies from vaccinated healthy donors. To better understand the characteristics of the immunologic response against SARS-CoV-2 in patients post-CAR T, larger multicenter studies exploring both humoral and cellular immunity will be needed. JEWN, MI and JM are co-first authors and PV, HM and AR are co-senior authors. [Formula presented] Disclosures Munoz Physicians' Education Resource Honoraria;Seattle Genetics Honoraria;Bayer Research Funding;Gilead/Kite Pharma Research Funding;Celgene Research Funding;Merck Research Funding;Portola Research Funding;Incyte Research Funding;Genentech Research Funding;Pharmacyclics Research Funding;Seattle Genetics Research Funding;Janssen Research Funding;Millennium Research Funding;Gilea /Kite Pharma, Kyowa, Bayer, Pharmacyclics/Janssen, Seattle Genetics, Acrotech/Aurobindo, Beigene, Verastem, AstraZeneca, Celgene/BMS, Genentech/Roche. Speakers Bureau;Pharmacyclics/Abbvie, Bayer, Gilead/Kite Pharma, Pfizer, Janssen, Juno/Celgene, BMS, Kyowa, Alexion, Beigene, Fosunkite, Innovent, Seattle Genetics, Debiopharm, Karyopharm, Genmab, ADC Therapeutics, Epizyme, Beigene, Servier Consultancy;Targeted Oncology Honoraria;OncView Honoraria;Kyowa Honoraria. Bergsagel Oncopeptides Consultancy, Honoraria;Novartis Consultancy, Honoraria, Patents & Royalties human CRBN mouse;Pfizer Consultancy, Honoraria;Celgene Consultancy, Honoraria;Janssen Consultancy, Honoraria;Genetech Consultancy, Honoraria;GSK Consultancy, Honoraria. Wang Incyte Membership on an entity's Board of Directors or advisory committees, Research Funding;LOXO Oncology Membership on an entity's Board of Directors or advisory committees, Research Funding;Genentech Research Funding;InnoCare Research Funding;Novartis Research Funding;MorphoSys Research Funding;Eli Lilly Membership on an entity's Board of Directors or advisory committees;TG Therapeutics Membership on an entity's Board of Directors or advisory committees. Fonseca Juno Consultancy;Kite Consultancy;Aduro Consultancy;OncoTracker Consultancy, Membership on an entity's Board of Directors or advisory committees;GSK Consultancy;AbbVie Consultancy;Patent Prognosticaton of myeloma via FISH Patents & Royalties;Caris Life Sciences Membership on an entity's Board of Directors or advisory committees;Scientific Advisory Board Adaptive Biotechnologies Membership on an entity's Board of Directors or advisory committees;BMS Consultancy;Amgen Consultancy;Sanofi Consultancy;Merck Consultancy;Mayo Clinic in Arizona Current Employment;Celgene Consultancy;Takeda Consultancy;Bayer Consultancy;Janssen Consultancy;Novartis Consultancy;Pharmacyclics Consultancy. Palmer Sierra Oncology Consultancy, Research Funding;CTI BioPharma Consultancy, Research Funding;Protagonist Consultancy, Research Funding;Incyte Research Funding;PharmaEssentia Research Funding. Dingli Novartis Research Funding;GSK Consultancy;Apellis Consultancy;Alexion Consultancy;Sanofi Consultancy;Janssen Consultancy. Kapoor Sanofi Research Funding;AbbVie Research Funding;Takeda Research Funding;Karyopharm Consultancy;Cellectar Consultancy;BeiGene Consultancy;Pharmacyclics Consultancy;Sanofi Consultancy;Amgen Research Funding;Ichnos Sciences Research Funding;Regeneron Pharmaceuticals Research Funding;Glaxo SmithKline Research Funding;Karyopharm Research Funding. Kumar Roche-Genentech Consultancy, Research Funding;Oncopeptides Consultancy;Abbvie Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;BMS Consultancy, Research Funding;Beigene Consultancy;Celgene Membership on an entity's Board of Directors or advisory committees, Research Funding;Novartis Research Funding;Adaptive Membership on an entity's Board of Directors or advisory committees, Research Funding;Astra-Zeneca Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Tenebio Research Funding;Merck Research Funding;Carsgen Research Funding;KITE Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Janssen Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Takeda Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Amgen Consultancy, Research Funding;Bluebird Bio Consultancy;Antengene Consultancy, Honoraria;Sanofi Research Funding. Paludo Karyopharm Research Funding. Bennani Kymera Other Advisory Board;Vividion Other Advisory Board;Kyowa Kirin Other Advisory Board;Daichii Sankyo Inc Other Advisory Board;Purdue Pharma Other Advisory Board;Verastem Other Advisory Board. Ansell Bristol Myers Squibb, ADC Therapeutics, Seattle Genetics, Regeneron, Affimed, AI Therapeutics, Pfizer, Trillium and Takeda Research Funding. Lin Kite, a Gilead Company Consultancy, Research Funding;Merck Research Funding;Gamida Cell Consultancy;Takeda Research Funding;Juno Consultancy;Bluebird Bio Consultancy, Research Funding;Celgene Consultancy, Research Funding;Novartis Consultancy;Janssen Consultancy, Research Funding;Sorrento Consultancy;Legend Consultancy;Vineti Consultancy. Murthy CRISPR Therapeutics Research Funding.