**9.1 Venetoclax**

*Multiple Myeloma*

treatment [58].

observed [61].

of their thrombotic risk [8, 63].

**8. Follow-up and monitoring**

should be circumvented [8].

renal impairments [56, 57].

achieved [54, 55]. Denosumab doses can be administered at home if nursing facility is available or the patient should be trained for self-administration. Long-term discontinuation of denosumab treatment is associated with rebound effect and thus

Sufficient data are available that prohibits the use of bortezomib-based regimens in patients with baseline clinical renal impairments. However, evidences are lacking supporting the discontinuation of therapy in patients who develop drug induced

Severely anemic patients who do not respond to the conventional anemia management or deteriorating should be urgently switched to erythropoiesis stimulating agents (ESAs) in order to prevent the need for blood transfusions and frequent hospital visits. At present, the whole blood supplies has been extensively restricted due to the COVID-19 lockdown [8]. There are only few data advocating the use of ESAs in patients with persistent symptomatic anemia (hemoglobin <10 g/dL) where other causes of anemia have ruled out. Hence, ESAs should be discontinued after 6–8 weeks of therapy in patients' who fail to respond adequately to anemia

Immunization against influenza is recommended for specific infections caused by streptococcus pneumonia and hemophilus influenza, but sufficient data are lacking supporting the efficacy of the vaccination due to the fact that suboptimal

If patients are receiving PIs & ASCT, the prophylactic use of antiviral agents such as acyclovir (or valacyclovir) are highly recommended [8, 60]. Acyclovir should be prescribed according to local protocols. Immunoglobulin administration may be given in an individualized basis, depending on the depth of suppression of polyclonal immunoglobulins and patient history of recurrent infections [34].

Antiviral prophylaxis has to be recommended in drugs associated with increased risk of herpes zoster reactivation such as Daratumumab and PIs. The prophylaxis is recommended for at least 3 months after exposure if no contraindications are

Routine prophylaxis immunization should be considered with a series of pneumococcal conjugate vaccine 13 and pneumococcal polysaccharide vaccine, as well as annual influenza immunization [62]. Drugs such as IMiDs enhance the risk of venous thromboembolism, so preventive measures should be considered during active therapy [61], and the antithrombotic prophylaxis should be considered according to local or international guidelines. For countries with high incidence of COVID-19, low-molecular-weight heparin (LMWH) has to be preferred over aspirin as thromboprophylaxis in MM patients under IMiD administration, irrespective

Patients with a history of neutropenias and/or recurrent infections should receive

prophylactic G-CSF injections. Co-trimoxazole prophylaxis for Pneumocystis jirovecii for all patients and levofloxacin prophylaxis for the first three months of

Patients should be followed-up and monitored for complete blood counts (CBC), serum and urine electrophoresis with or without the use of serum-FLC determination, and also for serum calcium and creatinine measurements; at least in 2–3 months interval. In patients are complaining of bone pain, skeletal X-ray, MRI or CT scan should be carried out to detect and rule out new bone

treatment for NDMM patients are also highly recommended [8, 55].

immune responses are fairly seen after management [59].

**36**

lesions [64].

Venetoclax is an orally bioavailable selective B-cell lymphoma 2 (Bcl-2) inhibitor. Bcl-2 and cyclin D1 are over expressed in MM patients with a translocation of (11;14), which is present in approximately 20% of patients with MM [65]. Venetoclax is an antiapoptotic protein and an emerging and effective treatment for relapsed or refractory MM [66, 67], and also being tried for treatment of chronic lymphocytic leukemia (CLL) cells [66] and non-Hodgkin lymphoma (NHL) [65]. Although response rates with venetoclax-dexamethasone are impressive in patients with t(11;14), PIs, which inhibit induced myeloid leukemia cell differentiation protein (Mcl-1), have synergistic activity when combined with venetoclax [27].

Currently the venetoclax is suspended by the Food and Drug Administration (FDA) because of a report obtained from the BELLINI trial, which stated an increased relative risk of death in the venetoclax group. As more recent data are being collected to have a better understanding of the safety concerns raised by the BELLINI trial [27, 68].
