LAUSR

Multiple myeloma (MM) is the second most common blood cancer caused by the uncontrolled proliferation of clonal plasma cells. Despite recent advances in treatment, a majority of patients eventually relapse and die because of progressive disease (PD). Thus, the development of modern molecules with novel mechanisms of action is needed. The overexpression of antiapoptotic proteins (ie, Bcl-2, BclXL, Mcl-1) represents one of the hallmarks of cancer that favors tumor cell survival. It has been demonstrated that a subset of MM is Bcl-2 dependent. These are especially those harboring the t(11;14)— molecular subgroup which is associated with a high expression of Bcl-2 and a low expression of Bcl-XL and Mcl-1. 1,2 The presence of translocation t(11;14) is present in 15%-20% of newly diagnosed MM and even up in 50% of primary plasma cell leukemia. Venetoclax (ABT-199, Venclexta), a selective orally bioavailable Bcl-2 inhibitor, is one of the real game changers in cancer therapy. Venetoclax has demonstrated unprecedented efficacy across a majority of hematological malignancies. Venetoclax as a single agent has proved to be active in human MM cell lines, primary patient samples and RRMM patients, especially those positive for t(11;14). Triplet combination of venetoclax, bortezomib, and dexamethasone (Ven-VD) was examined in a phase 1b clinical trial enrolling 66 RRMM patients with a median of three previous therapies. The ORR was 65% in patients without t(11;14) and 78% in patients with t(11;14). Interestingly, ORR was 31% in patients refractory to prior bortezomib, and 11% in patients with more than six previous therapies. Relapsed refractory MM patients with exhausted treatment options were offered to receive venetoclax which was provided as part of a preapproval access program by Abbvie. A total of 11 patients were treated by Ven-VD regimen between December 2017 and September 2019 after IRB approval at University Hospital Ostrava (Table 1). All 11 patients were highly pretreated with a median of 7 (range 4-10) previous lines of therapy. Thirty-six percent (4/11) harbored high-risk cytogenetic abnormalities and all patients were t (11;14) negative. The median time from diagnosis to initiation of treatment was 6.1 years (range 3-12.8 years), the calculated median follow-up was 23 months. Venetoclax was administered orally at a dose of 800 mg/day. Bortezomib 1.3 mg/m was given on days 1, 4, 8, 11 and dexamethasone (20 mg orally) was given on days 1, 2, 4, 5, 8, 9, 11, 12. Patients were treated in 21-day cycles until disease progression or unacceptable toxicity. All patients had undergone bone TABLE 1 Baseline demographic and clinical characteristics of patients