COVID-19 Mortality Rates Rise With Hospitalization and Rituximab Treatment in MCL

The overall mortality rate for patients with mantle cell lymphoma (MCL) who contract COVID-19 is high, and mortality rates rise significantly in patients who are hospitalized or enter intensive care units (ICUs), according to findings from a retrospective study that were published in Hemasphere.

The findings indicated that, of 63 patients with MCL with evidence of a COVID-19 infection, the overall mortality rate was 44.4%. Of the 46 patients who were hospitalized because of COVID-19, the mortality rate was 61%. And, of the 16 hospitalized patients who needed ICU care, the mortality rate was 93.8%.

Additionally, patients who received rituximab (Rituxan), a CD20-directed antibody, as part of MCL treatment, exhibited poorer survival than those who did not receive rituximab (P = .04).

Since the advent of the global COVID-19 pandemic, patients with cancer are among those at increased risk of severe disease or death from the SARS-CoV-2 virus. Patients with lymphoma are often immunosuppressed by their active disease. Additionally, many standard treatment options for MCL, including chemotherapy and immunotherapy, are immunosuppressive, and other disease factors, such as neutropenia, lymphopenia, and hypogammaglobulinemia, may also contribute to immune deficiency in this population.

Specific information on the outcomes of patients with MCL who contract COVID-19 is currently limited, and data regarding immune recovery after prolonged immunosuppression from therapy is unclear. This retrospective, multicenter, international study aimed to identify potential mortality risk factors from COVID-19 in patients with MCL and gain insight on the potential effects of MCL treatments on patients with COVID-19.

Data were collected from 63 patients with MCL with a median age of 64 years (interquartile range, 44-84) at the time of COVID-19 infection from 9 countries of the European MCL (EMCL) network. Eligible patients showed evidence of a COVID-19 infection between February 2020 and October 2021. Mild COVID-19 infection was defined as the need for ambulatory care or hospitalization without the need for oxygen therapy. Severe COVID-19 infection was defined as hospitalization requiring oxygen therapy or admission to an ICU.

Of these studied patients, 87% (n = 55) were receiving some form of MCL treatment at the time of their COVID-19 infection. Of those 55 patients, 36.5% (n = 23) were receiving induction/consolidation therapy, 24% (n = 15) were receiving rituximab maintenance therapy, 24% (n = 15) were receiving novel drugs, and 9.5% (n = 6) were receiving no therapy. In total, 45 of these patients (71%) continued treatment throughout their COVID-19 infection.

Of the ambulatory patients (n = 17), 47% were receiving induction or consolidation therapy at the time of COVID-19 infection, 23.5% were not receiving treatment, 18% were receiving rituximab maintenance, and 12% were receiving therapy with novel drugs. A total of 65% (n = 11) of these patients were responding to MCL therapy, and 23.5% (n = 4) had active disease.

In terms of remission status, 70% (n = 44) of all patients studied had a complete remission (CR; 48%; n = 30) or partial remission (PR; 22%; n = 14), and 21% (n = 13) had stable disease (SD; 8%; n = 5) or progressive disease (PD; 13%; n = 8). A total of 77% (n = 34) of the patients in remission received a treatment regimen containing rituximab.

Regarding COVID-19 vaccination status, 14% of the studied population was vaccinated (n = 9), with 2 patients becoming infected with COVID-19 after vaccination and 7 patients receiving vaccination following recovery from COVID-19 infection. Of these 9 patients, 7 were receiving rituximab-based therapy, and 2 were not receiving any treatment at the time of vaccination. A total of 55% of vaccinated patients were hospitalized compared with 73% of the entire study cohort. Among these hospitalized patients, all were discharged, and no deaths were reported.

Seventy-three percent (n = 46) of all studied patients were hospitalized due to COVID-19 infection at a median 1.5 days (range, 0-365) following COVID-19 diagnosis. Of these patients, 20% (n = 9) did not require oxygen therapy, and 74% (n = 34) had severe COVID-19 infection. A total of 35% (n = 16) of patients were admitted to the ICU.

In terms of COVID-19–specific treatment, 43% (n = 27) of hospitalized patients received corticosteroids, 29% (n = 18) received antibiotics, 24% (n = 15) received remdesivir (Veklury), and 19% (n = 12) received convalescent plasma. Fourteen patients received mechanical ventilation. Notably, treatments were often combined. Of the 27 patients who received corticosteroids, 52% also received antibiotics, 48% also received remdesivir, and 37% also received convalescent plasma. Of the patients who received mechanical ventilation, 93% received corticosteroids, 57% received antibiotics, 50% received remdesivir, and 35% received plasma. All but 3 (17.6%) of the ambulatory patients were not treated with any COVID-19–specific therapies.

At a median follow-up of 26 days (range, 1-344), 28 patients had died, with 71.4% of these deaths occurring within the first 30 days of COVID-19 infection. The median age at COVID-19–related death was 65.8 years. However, the age of 65 years or greater was not significantly associated with increased mortality (hazard ratio [HR], 1.26-6.07; P = .89), although this conclusion may be influenced by the study’s small sample size.

Of these patient deaths, 86% (n = 24) were related to COVID-19 infection. Additionally, 11% (n = 3) of patient deaths were due to MCL, and 1 was due to other causes.

The mortality rate was 70.6% in patients classified with severe COVID-19 infection. Of the 14 patients requiring a ventilator, 13 died.

All 17 patients who were not hospitalized for COVID-19 survived the infection, displaying superiority in terms of overall survival (OS) compared with hospitalized patients. Of patients who were not hospitalized, 11 were in remission at the time of infection. Of the patients who were responding to treatment at the time of COVID-19 infection, 19 died of the infection. By contrast, the poorest survival outcomes were seen in patients with PD. A total of 54% (n = 7) of patients with active disease died of the infection.

Patients not undergoing active treatment at the time of COVID-19 infection did not have significantly superior outcomes compared with patients receiving induction, consolidation, maintenance, or novel drug therapies. However, patients who received regimens containing rituximab within 6 months of COVID-19 infection had a significantly lower OS than those who had not received rituximab within 6 months of infection (HR, 0.35; 95% CI, 0.129-0.9; P = .04). Of the 15 (24%) patients who had received rituximab, 7 died of COVID-19 infection.

In patients who survived COVID-19 infection, the observed long COVID-19 syndrome persisting symptoms included fatigue (43%; n = 15), reduced bone marrow function (20%; n = 7), and pulmonary symptoms (10%; n = 4). These symptoms often affect hematological patients receiving treatment regardless of COVID-19 infection. Patients with MCL typically need to achieve normal pulmonary capacity and adequate bone marrow function before beginning many lymphoma treatments. These results indicate that even if patients survive a COVID-19 infection, their long COVID-19 syndrome symptoms may prevent them from receiving subsequent MCL treatment.

The results of this study confirm the importance of COVID-19 prevention strategies for patients with MCL and highlight the need for early and diligent vaccination in this vulnerable population. In particular, the data regarding OS related to rituximab treatment highlight the potential negative effect of CD20 inhibition on immune strength and survival. Additionally, the prevalence of long COVID-19 in this population indicates potential barriers to subsequent MCL treatment, leading to higher mortality rates in patients who become infected with COVID-19.

Additional studies are needed to more accurately determine the effects of COVID-19 on vaccinated patients with MCL.

Reference

Tilch MK, Visco C, Kinda S, et al. Outcome of COVID-19 in patients with mantle cell lymphoma—report from the European MCL registry. Hemasphere. 2022;6(5):e0711. doi:10.1097/HS9.0000000000000711