Treatment of cll relapsed/refractory patients in covid-19 pandemic: A real-life experience with venetoclax-rituximab combination in southern Italy
Authors: S. Molica, P. Sportoletti, B. Martino, C. Patti, G. Mineo, D. Mannina, V. Leone, M. Musso, S. Siragusa, G. Palumbo, V. Minardi, P. Scalzulli, G. Tarantini, A. Maggi, I. Angeletti, A. Greco, L. Levato, M. Rossi, M. Gentile, C. Stelitano, C. Califano, C. Selleri, A. Rocino, A. M. Risitano, F. Chiurazzi, G. Farina, A. M. Giordano, A. L. Chiarenza, P. Musto, N. Direnzo, F. Pane, F. Diraimondo
Journal: HemaSphere (2021)

Background: Given the multifactorial immune defect characterizing chronic lymphocytic leukemia (CLL), it appears conceivable that these patients have risk factors that increase their likelihood of complications and death from COVID-19. Aims: To evaluate incidence and severity of COVID-19 cases in a well-defined cohort of patients with CLL receiving venetoclax-based combinations. Methods: We administered a survey to a cohort of CLL treating hematologists from hematological centers in southern Italy. Participants were asked: a) to indicate whether they had offered a test for detection of COVID-19 infection (mainly nasopharyngeal swabs) only to CLL patients who reported symptoms or universally;b) to provide information on the incidence of COVID-19 infection and its severity;c) to specify reasons of possible treatment modifications. The survey was restricted to relapsed-refractory (R/R) CLL patients treated from Feb 1st to Dec 31th 2020 with time-limited venetoclax/rituximab (VR) combination as recommended by MURANO protocol (venetoclax for up to 2 years plus rituximab for the first 6 months), within their clinical practice. Results: A specific questionnaire was sent to 30 CLL hematologists, but only 26 responded to all questions. We considered suitable for the present analysis the 24 questionnaires compiled by hematologists who declared to have treated at least one patient with VR combination in the observation period. Of those, 20.8% worked in academic hospitals. Overall, the survey allowed to collect data on 124 patients who were treated with VR combination. The median number of patients treated in each center was 5 (range,1-15).COVID-19 surveillance tests consisted of viral RNA reverse transcriptase PCR (RT-PCR) on nasopharyngeal swabs. Generally, a policy of universal SARS-CoV-2 testing to be performed on patients at different time-points of therapy was used. Most patients (83/124, 66.9%) were tested before beginning the ramp-up with venetoclax;moreover 66/124 (53.2%) were regularly tested before each rituximab infusion (Fig 1).Reasons for potential change of the schedule of treatment were also investigated. The survey revealed that adherence to treatment was relatively high (70.8%). Only 29.1% physicians modified the therapeutic program mainly because of grade 3 neutropenia. Changes consisted of transient interruption of venetoclax, reduction of doses, and delay of rituximab infusion.Only 2/124 patients (1.6%) had a symptomatic RT-PCR proven diagnosis of COVID-19 infection and required hospitalization. Both patients needed oxygen therapy and admission into an intensive care unit. Of those, 1 patient who was receiving VR combination at the time of COVID infection, eventually died. The second patient developed COVID-19 infection while receiving venetoclax monotherapy (after the VR combination period). He recovered from COVID-19 infection and after 21 days of treatment interruption, he was able to restart venetoclax. Summary/Conclusion: Results of the present survey provide information, thus far lacking, on the use in real-world clinical practice of VR combination during the COVID19 pandemic in 2020. Current literature on the prevalence of COVID-19 infection in CLL, has some limitations (i.e., small size sample, heterogeneity of treatment, restriction to only the first pandemic wave);this survey, performed on a large number of CLL patients treated with VR combination only seems to provide additional information on safe management of CLL treatment during the COVID19 pandemic.