ABSTRACT
High morbidity and mortality due to COVID-19 were described in the pre-vaccination era in patients with chronic lymphocytic leukemia (CLL). To evaluate COVID-19 morbidity after the SARS-CoV-2 vaccine, we carried out a prospective study in 200 CLL patients. The median age of patients was 70 years; 35% showed IgG levels ≤ 550 mg/dL, 61% unmutated IGHV, and 34% showed TP53 disruption. Most patients, 83.5%, were previously treated, including 36% with ibrutinib and 37.5% with venetoclax. The serologic response rates to the second and third dose of the vaccine were 39% and 53%, respectively. With a median follow-up of 23.4 months, 41% of patients experienced COVID-19, 36.5% during the Omicron pandemic, and 10% had subsequent COVID-19 events. Severe COVID-19 requiring hospitalization was recorded in 26% of patients, and 4% died. Significant and independent factors associated with the response to the vaccine and vulnerability to COVID-19 were age (OR: 0.93; HR: 0.97) and less than 18 months between the start of targeted agents and vaccine (OR: 0.17; HR: 0.31). TP53 mutation and ≥two prior treatments also emerged as significant and independent factors associated with an increased risk of developing COVID-19 (HR: 1.85; HR: 2.08). No statistical difference in COVID-19 morbidity was found in patients with or without antibody response to the vaccine (47.5% vs. 52.5%; p = 0.21). Given the persistent risk of infection due to the continuous emergence of SARS-CoV-2 variants, our results support the importance of new vaccines and protective measures to prevent and mitigate COVID-19 in CLL patients.
ABSTRACT
The GIMEMA phase II LLC1518 VERITAS trial investigated the efficacy and safety of frontline, fixed-duration venetoclax and rituximab (VenR) combination in young (≤65 years) and fit patients with chronic lymphocytic leukemia (CLL) and unmutated IGHV and/or TP53 disruption. Treatment consisted of the Ven ramp-up, six-monthly courses of the VenR combination, followed by six monthly courses of Ven single agent. A centralized assessment of measurable minimal residual disease (MRD) was performed on the peripheral blood (PB) and bone marrow (BM) by ASO-PCR at the end of treatment (EOT) and during the follow-up. The primary endpoint was the complete remission (CR) rate at the EOT. Seventy-five patients were enrolled; the median age was 54 years (range 38-65), 96% had unmutated IGHV, 9 (12%) had TP53 disruption, and 4% were IGHV mutated with TP53 disruption. The overall response rate (ORR) at the EOT was 94.7%, with a CR rate of 76%. An undetectable (u) MRD was recorded in 69.3% of patients in the PB and 58.7% in the BM. The 12-month MRD-free survival in the 52 patients with uMRD in the PB at the EOT was 73.1%. After a median follow-up of 20.8 months, no disease progressions were observed. Three patients have died, two due to Covid-19 and 1 to tumor lysis syndrome. The first report of the VERITAS study shows that frontline VenR was associated with a high rate of CRs and durable responses with uMRD in young patients with CLL and unfavorable genetic characteristics.