Low-Dose Venetoclax Under Study in Myeloma Harboring t(11;14) Translocation
Posted: Wednesday, June 30, 2021
Heavily pretreated patients with multiple myeloma and AL (amyloid light-chain) amyloidosis whose disease is marked by t(11;14) translocation responded to low-dose venetoclax monotherapy (400 mg daily), with manageable adverse effects, according to the results of a 25-patient study reported in the American Journal of Hematology. Evren Alici, MD, PhD, of Karolinska Institutet, Stockholm, and colleagues noted that the response rate, including partial responses or better, with the BCL2 inhibitor was 71% in AL amyloidosis (5 of 8 patients) and 33% in multiple myeloma (6 of 17 patients).
What’s more, the study authors believe that using “immunohistochemistry on bone marrow samples, at any stage of the disease and before the exposure to venetoclax, can provide clinicians with a simple tool to predict responses in multiple myeloma patients with t(11;14).” That tool is composed of BCL2/MCL1 and BCL2/BCL2-XL ratios.
Specifically, the ratio of the frequency of BCL2- and MCL1-expressing cells across all analyzed multiple myeloma samples was significantly higher (P = .031) in patients who later achieved a partial response or better with venetoclax versus those who did not (average ratio = 2.7 vs. 1.0, respectively). The ratios of the frequency of BCL2 and BCL-XL positive cells were also significantly higher (P = .021) at diagnosis in responders than in nonresponders (4.0 vs. 2.0, respectively).
The median time on treatment for the study’s 25 patients, all of whom had disease that was refractory to standard therapies, was 7.2 months; the median follow-up from the start of venetoclax treatment was 9 months. Patients who achieved a partial response or better remained on venetoclax treatment for more than 15 months and have not yet reached the “median of events.”
According to a press release from the Karolinska Institutet, 20 patients (80%) experienced some adverse events, although they were all considered to be manageable, and no deaths associated with venetoclax treatment were reported.
Disclosure: The study authors reported no conflicts of interest.
