Translocation t(11;14) Associated With Poorer Outcome in Bortezomib-Treated Newly Diagnosed Amyloid Light-Chain Amyloidosis


Key Points

  • Patients with the t(11;14) translocation who were receiving bortezomib-dexamethasone for newly diagnosed amyloid light-chain amyloidosis had poorer hematologic event-free and overall survival.
  • The multiple myeloma high-risk aberrations t(4;14), t(14;16), del(17p), and gain of 1q21 were not associated with worse outcome. 

In a single-institution study reported in the Journal of Clinical Oncology, Bochtler et al found that presence of the t(11;14) translocation on interphase fluorescence in situ hybridization (iFISH) was associated with poorer hematologic event-free and overall survival in patients receiving bortezomib (Velcade)-dexamethasone for newly diagnosed amyloid light-chain amyloidosis.

The study involved 101 consecutive patients receiving bortezomib-dexamethasone at University Hospital Heidelberg. Patients were ineligible for high-dose chemotherapy due to increased risk for cardiac or renal failure.

Poorer Outcomes

The t(11;14) translocation was present in 63% of patients and was associated with reduced hematologic event-free survival (median, 3.4 vs 8.8 months, P = .002), overall survival (median, 8.7 vs 40.7 months,  P = .05), and remission rate (≥ very good partial remission in 23% vs 47%, P = .02). On multivariate analysis including established hematologic and clinical risk factors, presence of the translocation was associated with significantly reduced hematologic event-free survival (hazard ratio [HR] = 2.94, P = .006) and overall survival (HR = 3.13, P = .03), but not reduced rate of remission (P = .22).

The multiple myeloma high-risk iFISH aberrations t(4;14), t(14;16), del(17p), and gain of 1q21 were not associated with adverse prognosis.

The investigators had previously reported a trend toward improved overall survival with melphalan-dexamethasone treatment in t(11;14)-positive patients at their institution.

The investigators concluded: “iFISH results are important independent prognostic factors in [amyloid light-chain] amyloidosis. In contrast to our recently published results with melphalan and dexamethasone standard therapy, bortezomib is less beneficial to patients harboring t(11;14), whereas it effectively alleviates the poor prognosis inherent to high-risk aberrations. Given the discrepant response to different treatment modalities, iFISH may help to guide therapeutic choices in these poor-risk patients requiring rapid hematologic response.”

Stefan O. Schönland, MD, of University Hospital Heidelberg, is the corresponding author for the Journal of Clinical Oncology article.

The study was supported by the Dietmar-Hopp Foundation “Heidelberger Konzept zur Optimierung der Diagnostik und Therapie des Multiplen Myeloms,” Bundesministerium für Bildung und Forschung, and Janssen-Cilag.

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