COVID-19 Severity and Survival over Time in Vaccinated Patients with Hematologic Malignancies

Introduction. The incidence, severity and mortality of coronavirus disease-2019 (COVID-19) has changed over time. The complex relations between new coronavirus variants and advances in detection, prevention and treatment impacted on patient characteristics and outcomes is unknown in hematological patients. Nonetheless, in unvaccinated patients with hematologic malignancies (HM), these rates were much higher than in the general population. We documented the COVID-19 pandemic dynamics in a previous population-based study performed in the Madrid region, Spain, in 1166 consecutive patients, and reported 30 and 60-day survival rates of 68% and 56% in unvaccinated patients with HM. In the present study we aimed to describe patient characteristics, severity and mortality in patients with HM and COVID-19 infection following vaccination roll-out.

Methods. Data from adult patients with HM and COVID-19 infection in the 16 months period from 2021, March 1^st to 2022, July 15^th were included in this observational study. Confirmed infection cases were reported by the Departments of Hematology of 10 Hospitals, members of the Madrid Regional Health Service (SERMAS) and affiliated with the Madrid Society of Hematology. The key data extracted for the purposes of this analysis were pre-infection patient characteristics, cancer type and treatment, and information on COVID-19 management. The key end points of the study were hospital admission, clinical severity of COVID-19, mortality (30-day mortality and 30- and 60-day survival probability estimates). Patients were analyzed according to time of COVID-19 diagnosis in three periods; those diagnosed from 1^st March 2021 through 30^th November 201, were defined as the delta cohort; patients diagnosed from December 1, 2021, to February 28, 2022, were defined as the early omicron cohort, and patients diagnosed from 1 March 2022 and 15 July 2022 were defined as the late omicron cohort.

Results. 346 out of 436 cases reported were included in this analysis. Median age was 66 years (IQR, 55 to 77), 47% were women and 17% had 2 or more comorbidities. The two most frequent HM were Non-Hodgkin Lymphoma (37%) and Multiple Myeloma (25%), and 18% myeloid neoplasms; 18% of patients received autologous or allogenic stem cell transplantation and 92% were on active cancer therapy in the 30-days prior to COVID-19 infection. None of the above patient characteristics showed significant (P <0.05) differences between periods [first period, n=42 (12%); second, n=123 (36%); and third, n=181 (52%)].

Overall, 94% of patients received at least one dose of COVID-19 vaccine. In the third period, 31% of patients were treated with Paxlovid.

Hospital admissions decreased in the second and third periods (34%) compared to the first period (57%), odds ratio 0.37 (0.19 to 0.72); clinical severity also decreased over time, severe and critical cases were respectively 4% and 21%, odds ratio 0.28 (0.14 to 0.56). 30, 60 and 90-day survival estimates were respectively 85%, 80% and 80% in the first period and 93%, 90% and 87% in the second and third period, hazard ratio 0.64 (0.30 to 1.33). None of the above comparisons between the second and third periods showed significant (P <0.05) differences. These estimated survivals were considerable higher regarding pre-vaccination periods 66% and 58% survival at 30 and 60 days. Increasing age over 60 years and having three or more comorbidities were the two patient characteristics we identified associated with higher clinical severity and lower survival. In the 70-79 age group, 30/60/90-day survival was 91% / 87% and 84%, hazard ratio 4.9 (1.1 to 22) compared to under 60 years old age group; > 80 years old survival was reduced to 80% (69 to 93), hazard ratio 7.2 (1.6 to 32).

Conclusions: Almost all patients with HM and COVID-19 have started a COVID-19 vaccination scheme. Since the vaccination roll-out was launched for patients with HM 15 months ago, more than half of the COVID-19 infection cases in patients with HM occurred in the last four months. We identified no cancer therapies feature associated with clinical outcomes. Clinical severity decreased over time; 30 and 60-day survival estimates were higher than in previously reported unvaccinated patients with HM. An ongoing overall analysis over time, since the start of the pandemic, is needed to fully assess the impact up to now of the COVID-19 pandemic in the highly vulnerable patients with HM.

Hernandez:Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Beigene: Membership on an entity's Board of Directors or advisory committees; Lilly: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz: Membership on an entity's Board of Directors or advisory committees; Rovi: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees. Alegre:Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Sanofi: Research Funding. Jiménez-Yuste:Roche, NovoNordisk, Sanofi, Sobi, Takeda, Grifols, Bayer, Pfizer, Octapharma, CSL Behring: Research Funding; Roche, Novo Nordisk, Sanofi, Sobi, Takeda, Grifols, Bayer, Pfizer, Spark, BioMarin, Octapharma, CSL Behring: Consultancy; Roche, NovoNordisk, Sanofi, Sobi, Takeda, Grifols, Bayer, Pfizer, Spark, Octapharma, CSL Behring: Honoraria.