Blood Cancer J 2021 Jan 11
Venetoclax induces deep hematologic remissions in t(11;14) relapsed/refractory AL amyloidosis.
Abstract
Venetoclax is efficacious in relapsed/refractory t(11;14) multiple myeloma, thus warranting investigation in light-chain amyloidosis (AL). This retrospective cohort includes 43 patients with previously treated AL, from 14 centers in the US and Europe. Thirty-one patients harbored t(11;14), 11 did not, and one t(11;14) status was unknown. Patients received a venetoclax-containing regimen for at least one 21- or 28-day cycle; the median prior treatments was three. The hematologic response rate for all patients was 68%; 63% achieved VGPR/CR. t(11;14) patients had higher hematologic response (81% vs. 40%) and higher VGPR/CR rate (78% vs. 30%, odds ratio: 0.12, 95% CI 0.02-0.62) than non-t(11;14) patients. For the unsegregated cohort, median progression-free survival (PFS) was 31.0 months and median OS was not reached (NR). For t(11;14), median PFS was NR and for non-t(11;14) median PFS was 6.7 months (HR: 0.14, 95% CI 0.04-0.53). Multivariate analysis incorporating age, sex, prior lines of therapy, and disease stage suggested a risk reduction for progression or death in t(11;14) patients. Median OS was NR for either subgroup. The organ response rate was 38%; most responders harbored t(11;14). Grade 3 or higher adverse events occurred in 19% with 7% due to infections. These promising results require confirmation in a randomized clinical trial.
Related Questions
What options are available for patients with relapsed/refractory AL amyloidosis after Dara-CyBorD, other than clinical trial?
No great answers, unfortunately. Lenalidomide still tends to make me a bit nervous in AL amyloidosis, as does carfilzomib in patients with known cardiac involvement. But pom-based regimens are an option, or carfilzomib-based in the appropriate population.If the patient's BMBx shows t(11;14) by FISH,...
How would one alter therapy in a transplant-ineligible AL amyloidosis with less than a complete response to six cycles of Dara-CyBorD?
If the patient has achieved deep VGPR (but perhaps not CR due to interference of dara), it is probably reasonable to continue dara maintenance as per ANDROMEDA as long as the patient is also clinically improving. If the response has not reached this level or the patient has not had evidence of impro...