The actual incidence of HBV reactivation following ruxolitinib therapy is unknown, because most clinical trials excluded the enrollment of patients with active HBV. coadministration of bleomycin, so that this combination has become contra-indicated [9]. Large phase 3 studies did not show pulmonary toxicity when BV was not combined with bleomycin [21, 23]. Varicella Zoster Virus (VZV) and Herpes Simplex Virus (HSV) infections are described as common side effect of BV, with an incidence of 1 1?10% [149]. Extensive or disseminated diseases have been reported [26, 27]; however, a clear causal relationship is usually doubtful because of the impact of many other risk factors in affected patients. Although not described in pivotal studies, two case series of cytomegalovirus (CMV) reactivation under BV have been published, questioning the true incidence of this event and a possible causal relationship. In allogeneic stem cell recipients, 5 CMV viremias among 25 patients treated with BV for HL recurring after allogeneic HSCT were reported. Three patients required treatment and one died in the setting of CMV reactivation [28]. Another report described three cases of CMV reactivation with retinitis among 32 lymphoma patients treated with BV. Patients responded to therapy, but two out of three relapsed after BV rechallenge [29]. Concerns about a risk of JC virus (John Cunningham polyoma virus) contamination in patients treated with BV have been raised early after the approval of BV. A boxed warning was inserted in the drug label in 2012. At that time, two confirmed and one probable case of progressive multifocal leukoencephalopathy (PML) had been reported among 2000 patients treated worldwide [30]. Additional cases have been described since then [31], with a total of 15 cases OCLN reported until July 2015 to the FDAs Adverse Event Reporting System. The case fatality rate was 33.3% [32]. It must be kept in mind that those reported cases do not prove a causal relationship, as lymphoid malignancy, multiagent chemotherapy or hematopoietic cell transplantation are PML risk ARV-825 factors [33]. While there is no estimated PML incidence known for patients with HL, the rate for ARV-825 those with NHL is usually estimated to be 8.3 (95% CI 1.71C24.24) per 100,000 person-years [34]. For clinical practice, no specific recommendation can be made with regards to antimicrobial prophylaxis. G-CSF prophylaxis should be considered when BV is used in combination with chemotherapeutic brokers. PcP prophylaxis is not required, if BV is usually given without concomitant treatment [35]. The same rule applies to HSV and VZV prophylaxis [36]. CMV should be taken into consideration in case of symptoms compatible with contamination, but no prophylaxis, routine monitoring or preemptive therapy can be recommended for patients undergoing treatment with BV. For JC virus, no prophylaxis is usually available, but clinicians should be alert and prompt a complete work-up in case of new-onset neurological symptoms suggestive of PML. BV should be withheld until PML has been excluded. In case of confirmation, BV should be discontinued with the aim to restore immunity against JC virus. In some cases this may be complicated by an immune reconstitution inflammatory syndrome [37]. However, in the case of BV-associated PML, due to underlying disease and previous or concurrent treatments, immune recovery is usually uncertain and the clinical course is usually unpredictable. PML cases should be notified to local competent authorities, in order to document this rare possible association. Immune checkpoint inhibitors Immune checkpoint inhibition (ICI) has introduced a new era of cancer therapy [38]. It represents a novel therapeutic concept, as the primary target is the crosstalk between immune cells and cancer cells in the tumor microenvironment. Two immune checkpoints are currently targeted by approved drugs: the programmed death 1 (PD-1)/PD-ligand 1 (PD-L1) axis ARV-825 as well as cytotoxic T-lymphocyte antigen-4 (CTLA-4). Blockade of the PD-1 or PD-L1 pathway has.