The Effectiveness of Bivalent mRNA Omicron Containing Booster Vaccines Among Patients With Hematological Neoplasms

Results and Discussion

The total cohort included 10770 patients with hematological malignancies (active, in watch and wait, or remission). Of those, 1988 patients (18.5%) received the Omicron booster. During the study period, 485 patients were infected with Omicron. Thirteen out of 485 patients were tested positive while hospitalized, and, therefore, excluded from the cohort. Out of 472 patients in the cohort, only 70 patients received the bivalent mRNA booster. Table I presents the characteristics of the study cohort. The participants in the bivalent recipient group tended to be older, had a higher socioeconomic status score [ranging from 1 (lowest) to 10 (highest)], and previously received more doses of COVID-19 vaccines. The socioeconomic status score is based on several parameters including household income, educational qualifications, household crowding, material conditions, and car ownership. The type of hematological neoplasms has not affected the vaccine uptake (except for patients with mycosis fungoides that tend to have a higher vaccination rate), nor did the comorbidities.

The association between bivalent vaccine and COVID-19–related hospitalization was tested using a multivariable Cox proportional-hazards regression model and is presented in Table II. According to the results, fewer bivalent recipients needed COVID-19–related hospitalization [2 of 70 (2.9%)] than non-bivalent recipients [42 of 402 (10.4%)] with p-value=0.0304. This represents an 89% relative risk reduction in COVID-19–related hospitalization.

It should be noted that the number of doses of previous COVID-19 vaccines was not found to be statistically significant nor the time passed since the last COVID-19 mRNA vaccine booster (not including the bivalent mRNA booster examined here). This may be explained by the fact that the median time since the last mRNA vaccine booster was 340 days and vaccine waning was already seen in previous research (6).

However, an older age, being treated for hematological neoplasms in the last 12 months, and comorbidities of renal failure or chronic heart failure were all associated with a higher rate of COVID-19–related hospitalization (see p-values in Table II). One infected and unvaccinated patient received Anti-CD20 monoclonal antibodies during the study period. This patient was admitted to the hospital four days post-infection and was discharged 10 days later. The median duration of hospitalization was 7 days for the non-vaccinated group and 4 for the vaccinated group.

B-cell lymphoproliferative disorders are associated with a 46% higher risk for COVID-19 related hospitalization. However, it was not statistically significant (p-value=0.066; >0.05) according to the Cox model after adjustment for confounding factors. Bivalent vaccination was effective among patients with B-cell lymphoproliferative disorders and reduced the risk of COVID-19–related hospitalization by 87%. In addition, the risk reduction among non-B-cell lymphoproliferative disorders was 94%.

Figure 2 shows the mortality curve: eight patients (2%) from the non-vaccinated group and one patient (1.4%) from the vaccinated group deceased. However, the number of deceased was too small to be statistically significant. The median age of the deceased patients was 86 years. Six patients were hospitalized for COVID-19 before death. The deceased from the vaccinated group was not hospitalized before death, and he was the oldest patient who passed away (age=91 years).

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Figure 2.

Cumulative hazard ratio for Covid-19 hospitalization and mortality following infection. A) Cumulative hazard ratio for COVID-19-related hospitalization among vaccinated and non-vaccinated patients. Statistical significance was calculated using the Log Rank test. B) Cumulative hazard ratio for mortality due to any reason during 30 days follow-up since infection.

In addition, treatment with nirmatrelvir+ritonavir within five days from infection reduced the risk of hospitalization by 76%. These results support our previous report on patients with Chronic Lymphocytic Leukemia (CLL) and the protective role of anti-viral therapy (13).

We examined the safety concern for ischemic stroke that was recently raised by Food and Drug Administration (FDA), and Centers for Disease Control and Prevention (CDC) in our cohort (14). In total, 12 events of ischemic stroke were recorded in our database. One ischemic stroke occurred within 30 days after vaccination (1 out of 1,988 vaccinated patients, crude risk of 0.05%). Four ischemic strokes occurred in the first 30 days period in the unvaccinated group (4 out of 8,782, crude risk of 0.046%). We could not confirm a statistically significant increase in ischemic stroke rates due to vaccination.

Our study has several limitations. Because this is a retrospective cohort study, various confounders may have contributed to bias in the observed results. Specifically, unmeasured confoundings might exist, such as access to vaccination. Only a small portion of the patients received the bivalent vaccination. Bivalent administration was significantly higher among older patients. As Pfizer-BioNTech was the primary supplier in Israel during the study period, we only analyzed their mRNA bivalent vaccine and ignored the very few patients that received Moderna bivalent booster. The study ignored patients with positive rapid antigen test, that were not followed by a positive PCR. The study captured only relatively few mortality events, with very wide confidence intervals, thus we could not confirm the usefulness of the bivalent vaccine in reducing mortality. Nevertheless, our results suggest that the bivalent Omicron-containing vaccine mRNA booster effectively prevents hospitalization in patients with hematological malignancies.