Risk is equally high for patients in ’watch and wait’ mode after prior treatment

The risk of death from Covid-19 in patients with chronic lymphocytic leukemia (CLL) is high, whether patients are receiving active therapy at the time of infection, have previously received CLL treatment, or are being treated with a “watch-and-wait” approach, a multicenter, an international descriptive study found.

At a median follow-up of only 16 days (range, 1-43 days), the mortality rate for patients on active CLL-directed therapy at the time of Covid-19 diagnosis was 28%, Anthony Mato, MD, Memorial Sloan Kettering Cancer Center, New York City, and multi-center colleagues reported in Blood. Case fatality rates were similar for patients who had ever received CLL-directed therapy at 32% and for watch-and-wait patients at 37%, they added.

The overall-case fatality rate for the current series of 198 patients was 33%, but it was 37% among patients requiring hospital admission. However, as investigators pointed out, this is likely an under-estimation of the true case fatality rate for those hospitalized with Covid-19, as 49 patients who had been admitted to hospital because of the infection remained as inpatients at the time of analysis, Mato and colleagues noted. For the 129 patients who had been discharged or who had died at the time of the analysis, the case fatality rate was 50%.

“CLL patients have impaired humoral and cellular immune function, [so] we hypothesized that this cohort might be at particular risk of severe Covid-19 with its associated morbidity, including superimposed infections, and mortality,” the authors explained. “These data suggest that the subgroup of CLL patients admitted with Covid-19, regardless of disease phase or treatment status, are at high risk of death.”

International Centers

CLL patients who were diagnosed with symptomatic Covid-19 from 43 different international centers were included in the analysis and had the following characteristics:

  • The median age at initial diagnosis of CLL was 63 years (range, 35-92 years) while the mean age at the time of Covid-19 diagnosis was 70.5 years (range, 38-98 years).
  • Ninety percent of patients in the analysis required admission to the hospital.
  • The majority of the group (61%) had previously received at least one line of CLL therapy, and 45% were on active CLL therapy when diagnosed with the infection.
  • Approximately three-quarters of those on active therapy at the time of diagnosis were receiving a Bruton tyrosine kinase (BTK) inhibitor.

“Many patients had a significant burden of comorbidities, with a median CIRS (cumulative illness rating score) of 8 (range, 4-32),” the research team observed. Specifically, among patients with CLL included in this study:

  • Approximately half of the group had hypertension.
  • 44% had hypogammaglobulinemia.
  • 20% had a history of arrhythmia.
  • 20% had diabetes.
  • 17%% had either asthma or chronic obstructive pulmonary disease.
  • 17% had chronic renal disease.

On presentation, 88% of patients had fever, 85% of patients had cough, and more than 70% of patients reported fatigue and dyspnea, while 36% complained of myalgia or arthralgia. Mato and colleagues noted that the rates of hospital admission, ICU admission, and intubation were very similar between patients who had previously received treatment for CLL and the watch-and-wait group.

Of the 178 patients who required hospital admission, 92% required supplemental oxygen, 38% required admission to the intensive care unit (ICU), 27% needed IV vasopressor support, and 11% required dialysis.

As has been seen in other Covid-19 cohorts, death rates for patients who required supplemental oxygen, intubation, and mechanical ventilation were 39%, 43%, and 55%, respectively, and all were higher than they were for those who did not require the same level of intensive care.

The authors had anticipated that BTK inhibitor use might favorably affect overall survival (OS). However, in this particular cohort, BTK inhibitors did not appear to affect survival outcomes, although the majority of those who were receiving BTK inhibitor therapy at the time of diagnosis had their drug withheld.

The authors also found that, within their CLL-specific inpatient group, individual risk factors associated with a poor prognosis included advanced age of 75 years and older, a CIRS score in excess of 6, chronic renal disease, and asthma.

“These data show that known risk factors from non-cancer population-based data also modulate outcomes in CLL patients,” Mato and colleagues observed.

Indeed, the mortality rates observed in this particular cohort of CLL patients appeared to be at least similar to those from a large series of “all comer” symptomatic Covid-19 patients requiring hospitalization, as they pointed out.

The authors acknowledged that the follow-up of this particular patient group is short and will require a longer interval to better appreciate the impact of Covid-19 infection on patients with CLL.

Management of the infection was also variable across the different international settings.

Given that there was (and still is) no established standard of care for Covid-19 management, investigators could not comment on the optimal management strategy for patients infected with Covid-19.

Commenting on the study, Emili Montserrat, MD, University of Barcelona, Spain, underscored the fact that the case fatality rate of patients requiring hospital admission (37%) in the current study was “remarkably similar” to the case fatality rate of 36.4% reported among a cohort of symptomatic CLL patients in Europe.

“Not surprisingly,” Montserrat noted, the death rate was higher in patients with severe Covid-19 (over 60%) than in those with milder course of infection (38.5%) in the same CLL study group. Interestingly, the death rate in patients with any type of cancer was much lower (5.6%) in a large series of Covid-19-infected patients from China.

“These data support the notion that some patients with CLL are at increased risk to develop severe/critical Covid-19,” Montserrat noted. “However, this should not be interpreted as the destiny of [all] CLL patients,” he said. He also cautioned that physicians need to carefully weigh the risks and benefits of continuing CLL treatment among patients receiving treatment at the time of Covid-19 diagnosis — “keeping in mind that active, uncontrolled CLL with severe Covid-19 is the worst possible scenario.”

In patients who do require treatment, Montserrat recommended the use of ibrutinib as the best treatment option.

“An important caveat is that patients may die not because of Covid-19, but with Covid-19,” he pointed out. “Meanwhile, and as long as the Covid-19 outbreak persists, patients with CLL should maintain standard preventive measures… and be managed, wherever possible, in CLL reference centers with Covid-19-free facilities and telemedicine resources,” Montserrat advised.

  1. Case fatality rates among CLL patients infected with Covid-19 were high regardless of treatment status.
  2. Risk factors for illness severity and mortality from Covid-19 appear to be shared between CLL patients and Covid-19 patients without cancer.

Pam Harrison, Contributing Writer, BreakingMED™

The study was supported in part by the National Institutes of Health and the National Cancer Institute.

Mato reported receiving grants, personal fees, or other funds from TG Therapeutics, Pharmacyclics, Janssen, Genentech, AbbVie, Adaptive, Astra Zeneca, Celgene, Loxo, Sunesis, Regeneron, and BeiGene.

Montserrat had no competing financial interests to declare.

 

Cat ID: 118

Topic ID: 78,118,118,466,935,190,926,192,927,925,934