Cytomegalovirus‐specific T‐cell immunity and DNAemia in patients with chronic lymphocytic leukaemia undergoing treatment with ibrutinib

Assessment of the potential value of plasma Torque Teno virus DNA load monitoring to predict Cytomegalovirus DNAemia in patients with hematological malignancies treated with small molecule inhibitors: A proof-of-concept study

“…Nevertheless, the low number of patients developing CMV DNAemia from whom TTV DNA load measurements at day +15 were available (n=3) limits the soundness of our observation. The apparent lack of association between the magnitude of TTV DNA loads and CMV DNAemia risk in both patient groups is consistent with our previously reported data on CMVspecific T cell immunity in these patients 19,20 , showing no correlation between TTV DNA loads and CMV pp65/IE-1 IFN-γ-producing CD8 + and CD4 + T cell counts. Of note, peripheral blood levels of both CMVspecific functional T cell subsets were predictive of the risk of CMV DNAemia in SOT 29 and allo-HSCT settings 22 , but not in ibrutinib or ruxolitinib-treated patients 19,20 .…”

“…Third, as a proof-of-concept approach, we sought to determine whether the occurrence of CMV DNAemia could be anticipated via TTV DNA load measurements carried out at different time points after treatment inception. In this context, we previously demonstrated that hematological patients undergoing treatment with molecular targeting agents are at increased risk of developing low-level CMV DNAemia 19,20 . Since CMV DNAemia was detected at a median of +45 and +30 days after ibrutinib and ruxolitinib administration, respectively, we focused on TTV DNA loads quantified at baseline, and days +15 and +30.…”

“…All patients were CMVseropositive (at baseline) with hematologic malignancies that were treated with ibrutinib (n=20, all with B cell chronic lymphocytic leukemia; median age, 70 years; range, 48-86) or ruxolitinib (n=21; median age, 65 years; range, 22-93) as first-line therapy or after conventional chemotherapy. Relevant patient characteristics were previously reported 19,20 and are summarized in Table 1. The study period comprised the first 180 days after treatment initiation.…”

“…To our knowledge, there is no published information regarding the potential clinical value of TTV DNA load monitoring to anticipate the development of infectious events in patients treated with molecular targeting agents. Here, we profiled plasma TTV DNA load kinetics in hematological patients treated with ibrutinib or ruxolitinib and assessed whether TTV DNA load monitoring in these patients could predict the occurrence of Cytomegalovirus (CMV) DNAemia, an event frequently developed in these patients 19,20 , as may be the case in SOT and allo-HSCT recipients 12,21 .…”

Effects of B-Cell Lymphoma on the Immune System and Immune Recovery after Treatment: The Paradigm of Targeted Therapy

“…Finally, the emergence of infectious complications during ibrutinib therapy appears to be concentrated especially in the first 6–12 months of treatment [ 87 , 88 , 89 ]. In patients with CLL, cytomegalovirus end-organ disease has been anecdotally reported [ 90 ]. In a prospective study, plasma cytomegalovirus (CMV) DNAemia was detected in 30.4% of cases, but no patients developed either recurrent CMV DNAemia or CMV-related organ disease during the 180 days after starting ibrutinib.…”