Venetoclax induces deep hematologic remissions in t(11;14) relapsed/refractory AL amyloidosis

Vikram J. Premkumar, Suzanne Lentzsch, Samuel Pan, Divaya Bhutani, Joshua Richter, Sundar Jagannath, Michaela Liedtke, Arnaud Jaccard, Ashutosh D. Wechalekar, Raymond Comenzo, Vaishali Sanchorawala, Bruno Royer, Michael Rosenzweig, Jason Valent, Stefan Schönland, Rafael Fonseca, Sandy Wong, Prashant Kapoor

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number10
JournalBlood cancer journal
Volume11
Issue number1
DOIs
StatePublished - Jan 2021

ASJC Scopus subject areas

  • Hematology
  • Oncology

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