Nirmatrelvir/Ritonavir in Patients With Hematologic Malignancies Improves COVID-19 Outcomes

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Early treatment administration with this regimen also promoted a faster decrease in viral load and shorter viral shedding in patients with hematologic diseases who were positive for COVID-19.

Patients who have hematologic malignancies, whether they received hematopoietic stem cell transplantation or not, have been significantly impacted by COVID-19. Patients who receive anti-CD38 or anti-BCMA therapies experience an impairment in immune cells, which results in an inability to produce sufficient cellular and humoral responses to COVID-19 vaccination. A study published in Influenza and Other Respiratory Viruses compared the clinical characteristics, viral load, and outcomes in patients infected with non-severe COVID-19 infection (Omicron variant) with hematologic malignancies who were treated with either remdesivir (Veklury; Gilead Sciences) or nirmatrelvir with ritonavir (Paxlovid; Pfizer).

Antiviral oral drug -- Image credit: shidlovski | stock.adobe.com

Image credit: shidlovski | stock.adobe.com

This observational cohort study enrolled 83 adult patients with high-risk hematologic malignancies who were diagnosed early with COVID-19 and who received treatment with an antiviral regimen. Early diagnosis of COVID-19 was defined by a cycle threshold (Ct) value lower than 28 in real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) or a Ct value that ranges between 28 and 30 with positive sub-genomic RNA. Further, all patients included did not have supplemental oxygen therapy at virus onset.

High-risk hematologic malignancies included acute leukemia under intensive chemotherapy; lymphoma either in treatment or in remission with rituximab therapy; multiple myeloma under active treatment; chronic lymphocytic leukemia with targeted therapies; high-risk myelodysplastic syndrome in active treatment; and primary high-risk myelofibrosis. In addition, patients were also considered to be high risk of they had received a chimeric antigen receptor (CAR) T-cell therapy either within the first year of an allogenic hematopoietic stem cell transplantation (allo-HSCT) or the initial 6 months of an autologous stem cell transplant (ASCT).

All enrolled patients had a confirmed COVID-19 diagnosis by either a rapid antigen test or rRT-PCR (performed 5 days after antivirals were administered to both treatment groups) on both nasal and oropharyngeal throat swabs. In addition, patients with a positive rRT-PCR and Ct value greater than 26 underwent viral subgenomic RNA (sgRNA) testing. If rRT-PCR testing was not available, rapid antigen tests were performed on patients who received nirmatrelvir with ritonavir at the end of a 5-day antiviral regimen to assess the persistence of viral shedding. All patients with hematologic malignancies underwent continuous testing until negativization—when rRT-PCR showed either a Ct equal to or greater than 40 or a rRT-PCR Ct greater than 26 with a negative viral sgRNA—was achieved to determine the duration of viral shedding.

Antiviral regimens were administered to all patients with high-risk hematologic malignancies and a SARS-CoV-2 infection who demonstrated either a Ct less than 28 in rRT-PCR or positive sgRNA at diagnosis, or infection duration of 10 days or less of symptom onset. Between December 2021 and April 2022, regimens were remdesivir-based, and between May 2022 and August 2022 were nirmatrelvir and ritonavir-based. In addition, patients who were seronegative with either a Ct less than 26 or a positive sgRNA also received convalescent plasma with or without sotrovimab.

According to the analysis, approximately 39.8% of the 83 patients were older than 65 years, and most patients (94%) had received a prior COVID-19 vaccine, and 15 (18.1%) had a previous positive COVID-19 diagnosis. Approximately 44.6% of patients had a positive serology at diagnosis and most (90.4%) were symptomatic with symptoms such as fever, cough, pharyngitis, and rhinorrhea. The median (IQR) duration of symptoms prior to a positive test result was 0 days (0-2 days), while median time from diagnosis to treatment onset was 1 days (0-4 days), 2 days (1-5 days) in remdesivir-based regimen, and 1 days (0-3 days) in the nirmatrelvir with ritonavir-based antiviral regimen.

Key Takeaways

  1. Impact of COVID-19 on Patients with Hematologic Malignancies: Patients with hematologic malignancies, regardless of whether they underwent stem cell transplantation, face significant challenges when infected with COVID-19. The impairment in immune cells due to anti-CD38 or anti-BCMA therapies contributes to inadequate immune responses to COVID-19 vaccination, posing a risk to these patients.
  2. Treatment Strategies and Outcomes: The study compared the clinical characteristics, viral load, and outcomes of patients with high-risk hematologic malignancies infected with the Omicron variant of COVID-19. Patients received either remdesivir or nirmatrelvir with ritonavir as antiviral treatment. The analysis focused on early-diagnosed cases with specific criteria for eligibility, including Ct values from PCR testing and absence of oxygen therapy at virus onset.
  3. Comparison of Treatment Regimens: The findings revealed differences in patient characteristics and treatment outcomes between those who received remdesivir and those who received nirmatrelvir with ritonavir. Notably, patients treated with remdesivir tended to be younger, have acute leukemia, and receive different adjunctive therapies compared to those treated with nirmatrelvir with ritonavir. Despite similar Ct values prior to treatment initiation, the duration of active SARS-CoV-2 was longer in the remdesivir group compared to the nirmatrelvir with ritonavir group, suggesting potential differences in treatment efficacy or viral clearance.

Of the enrolled patients, 42 received treated with the remdesivir-based antiviral regimen, and the remaining 41 received the nirmatrelvir with ritonavir-based regimen. According to the analysis, patients in the remdesivir group were more likely to be younger, have acute leukemia, were less frequently vaccinated (3 doses), and had received prior treatment with corticosteroid less frequently than the nirmatrelvir with ritonavir group. In addition, patients in the remdesivir group were also more likely to receive corticosteroids, hyperimmune plasma, and sotrovimab.

Further, median Ct values prior to antiviral treatment were similar between both groups (remdesivir: 19 [17-23]; nirmatrelvir with ritonavir: 21 [17-24]), however, there was a greater difference in 5-day median Ct values (remdesivir: 26 [23-29]; nirmatrelvir with ritonavir: 33 [30-37]). Median duration of active SARS-CoV-2 documented by rRT-PCR, antigen testing, or sgRNA were 18 (13-23) days and 11 (8-11) days in the remdesivir and nirmatrelvir with ritonavir groups, respectively. According to the investigators, only 1 patient died during the trial, but the patient was in palliative care and the death was likely a result of Hodgkin lymphoma and end-stage renal cell carcinoma.

Limitations include the trial’s design (not a randomized, double-blind study), missing Ct values in some patients, and the trial was limited to enrolling patients from 1 medical center. Further, the authors note that vaccination rates were similar across the 2 cohorts with only 46.3% and 66.7% of patients in the remdesivir and nirmatrelvir with ritonavir groups, respectively, presenting positive SARS-CoV-2 serology at admission. The authors suggest that this is likely due to the underlying hematologic diseases in patients, thus hindering viral clearance.

Reference
Aiello, TF, Peyrony, O, Chumbita, M, et al. (2024), Real-Life Comparison of Antivirals for SARS-CoV-2 Omicron Infection in Patients With Hematologic Malignancies. Influenza Other Respi Viruses, 18: e13264. doi:10.1111/irv.13264
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