Impact of disease treatment on the outcome of patients with chronic lymphocytic leukemia (cll) with covid‐19: a multicenter study on behalf of gellc

Introduction: Patients (pts) with CLL are at risk of more severe COVID-19 clinical forms and worse survival compared to general population. Besides age and comorbidities, CLL treatments can aggravate an immune status otherwise impaired by the disease itself, which could also influence COVID-19 outcome. The aim of our study was to focus on COVID-19 outcomes according to CLL treatment at the time of COVID-19. Patients and Methods: 321 pts with CLL and COVID-19 from 52 Spanish centers were included. Pts were classified in two cohorts according to time of COVID. First cohort were pts from the first wave (1W) of COVID and included 166 pts infected from March 1 to May 31, 2020; the second wave (2W) included 155 patients infected from August 1 to January 31, 2021. Clinical characteristics, CLL treatment status and COVID outcomes were analyzed and reported from the whole series, and from the two cohorts separately. Finally, we collected data referred to SARS-CoV-2 infection status and response, including Polymerase Chain Reaction (PCR) negativity for COVID19 and presence of serum neutralizing antibodies. Results: Median age was 73 years (37-94) and 65% (n = 210) were male. A total of 160 (50%) were on watch and wait (W&W) approach, 61 (19%) were previously treated [26 of them (43%) ended treatment <12 months before COVID], and 100 (31%) were on active CLL treatment at the time of COVID diagnosis (72 BTKi, 16 BCL-2i, 9 alkylating drugs and 3 others). 1W cohort presented with more pneumonia (87% vs. 72%, p = 0.001), supplemental oxygen requirements (82% vs. 70%, p = 0.018) and admissions (92% vs 71%, p < 0.01) than those from 2W. Conversely, no significant differences in overall survival (OS) were found between the two cohorts. Considering the whole series, age and D-dimer levels were statistically associated with OS (p < 0.01). In addition, W&W patients presented better OS compared to patients on active or previous CLL treatment finished <12 months prior COVID infection (HR 1.7 [95% CI 1.09-2.81], p = 0.02). Finally, median time to PCR negativity was 33 days for W&W patients compared to 55 days for treated patients (p = 0.01) (Figure 1). Serological test was performed in 84 out of 321 cases (26%), with 47 patients (56%) becoming positive (IgG+). No significant differences in terms of seroconversion were found according to CLL treatment status. With a median follow-up of 60 days (range 0-320), no SARS-CoV-2 reinfections were reported and, among IgG+ cases, none of the patients became seronegative. Conclusions: CLL remains a high-risk disease for COVID-19 regardless of best understanding of SARS-CoV-2 management and improved health-care conditions during the 2W. Of note, patients in W&W have better OS compared to those previously treated or in active treatment at COVID diagnosis, suggesting that CLL treatment is worsening COVID-19 outcomes. Finally, PCR clears earlier in W&W patients than in treated cases. Time to PCR negativity according to CLL status Keywords: Chronic Lymphocytic Leukemia (CLL) No conflicts of interest pertinent to the abstract.