Clinical Lymphoma, Myeloma & Leukemia, Vol.21, Suppl.1 - September 2021

S137 In general, prophylactic antibiotics are not recommended for patients with CLL. However, pneumocystis prophylaxis with, e.g., cotrimoxazole, should be considered for patients treated with purine analogues or Pi3K  inhibitors, while herpes prophylaxis with, e.g., acyclovir, should be considered for patients with a prior history of herpes upon treatment. Furthermore, patients should be tested for chronic hepatitis B infection prior to any therapy, as reactivation of hepatitis B infection poses significant risks for patients with CLL upon treatment. 11 For patients experiencing neutropenia during therapy with chemoimmunotherapy and targeted treatment, granulocyte colony-stimulating factor (G-CSF) should be considered. Prediction of Infections in CLL Attempting to identify patients with CLL at the highest risk of serious infections, we have recently developed the machine learning algorithm CLL-TIM.org (CLL Treatment Infection Model). 7 By combining standard diagnostic workup in CLL, including IGHV status, with routine laboratory tests and medical history, in terms of pathology and microbiology diagnoses, CLL-TIM can identify approximately 20% of newly diagnosed patients with CLL as at high risk of serious infections and/or need for CLL treatment within two years of diagnosis. No similar algorithms have yet been developed for the prediction of risk of infections upon therapy for CLL. Recent work has suggested that certain recurrent mutations in CLL may be associated with a higher risk of fatal infections upon chemoimmunotherapy. 22 We are currently working on incorporating OMICs data with the CLL-TIM algorithm to provide ongoing risk assessments for infections during the different stages for treatment-naïve and treated patients with CLL. Changing the Natural History of Immune Dysfunction in CLL Employing the CLL-TIM algorithm, patients with a high (>65%) risk of infection and/or need of CLL treatment within 2 years of diagnosis are currently enrolled for the phase II, randomized, investigator-initiated clinical trial PreVent-ACaLL (ClinicalTrials. gov: NCT03868 7 22). 23 The primary endpoint of the trial is grade  3 infection-free survival for patients in the treatment arm compared to the observation arm after 24 weeks (12 weeks after end of treatment). Thus, the aim of the trial is to improve immune function for patients with CLL by short-term (12 weeks) treatment with the BTK inhibitor acalabrutinib and the BCL-2 inhibitor venetoclax. Other clinical trials, such as the CLL12 and EVOLVE trials, are currently testing preemptive treatment for patients with high-risk CLL, as assessed by CLL-IPI; 24,25 but, to our knowledge, PreVent-ACaLL is the first clinical trial aiming at improving the natural history of immune dysfunction in CLL. References 1. Herndon TM, Chen SS, Saba NS, et al. Direct in vivo evidence for increased proliferation of CLL cells in lymph nodes compared to bone marrow and peripheral blood. Leukemia. 201 7 ;31(6):1340-134 7 . 2. da Cunha-Bang C, Simonsen J, Rostgaard K, Geisler C, Hjalgrim H, Niemann CU. Improved survival for patients diagnosed with chronic lymphocytic leukemia in the era of chemo-immunotherapy: a Danish population-based study of 10455 patients. Blood Cancer J. 2016;6(11):e499. 3. Andersen MA, Rostgaard K, Niemann CU, Hjalgrim H. Antimicrobial use before chronic lymphocytic leukemia: a retrospective cohort study. Leukemia. 2021;35(3): 7 4 7 - 7 51. 4. Andersen MA, Eriksen CT, Brieghel C, et al. Incidence and predictors of infection among patients prior to treatment of chronic lymphocytic leukemia: a Danish nationwide cohort study. Haematologica. 2018;103( 7 ):e300-e303. 5. Aarup K, Rotbain EC, Enggaard L, et al. Real-world outcomes for 205 patients with chronic lymphocytic leukemia treated with ibrutinib. Eur J Haematol. 2020. 6. Fischer K, Al-Sawaf O, Bahlo J, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019;380(23):2225-2236. 7 . Agius R, Brieghel C, Andersen MA, et al. Machine learning can identify newly diagnosed patients with CLL at high risk of infection. Nat Commun. 2020;11(1):363. 8. Svanberg R, Janum S, Patten PEM, Ramsay AG, Niemann CU. Targeting the tumor microenvironment in chronic lymphocytic leukemia. Haematologica. 2021. 9. Andersen MA, Moser CE, Lundgren J, Niemann CU. Epidemiology of bloodstream infections in patients with chronic lymphocytic leukemia: a longitudinal nation-wide cohort study. Leukemia. 2019;33(3):662-6 7 0. 10. Andersen MA, Niemann CU, Rostgaard K, et al. Differences and temporal changes in risk of invasive pneumococcal disease in adults with hematological malignancies: Results from a nationwide 16-year cohort study. Clin Infect Dis . 2021; 7 2(3):463-4 7 1. 11. Eichhorst B, Robak T, Montserrat E, et al. Chronic lymphocytic leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2021;32(1):23-33. 12. Scarfo L, Chatzikonstantinou T, Rigolin GM, et al. COVID-19 severity and mortality in patients with chronic lymphocytic leukemia: a joint study by ERIC, the Figure 1 Chronic lymphocytic leukemia (CLL) gradually develops from the premalignant state of monoclonal B lymphocytosis (MBL), with a formal cutoff at 5 billion clonal CLL cells per liter peripheral blood. Immune dysfunction and, thus, increased risk of infections (red arrows) can be demonstrated prior to diagnosis of CLL for treatment naïve patients and upon treatment.