Treatment of Multiple Myeloma with high-risk cytogenetics: a consensus of the International Myeloma Working Group
Sonneveld P (1), Avet-Loiseau H (2), Lonial S (3), Usmani S (4), Siegel D (5), Anderson KC (6), Chng WJ (7), Moreau P (8), Attal M (9), Kyle RA (10), Caers J (11), Hillengass J (12), San Miguel J (13), van de Donk NW (14), Einsele H (15), Bladé J (16), Durie BG (17), Goldschmidt H (18), Mateos MV (19), Palumbo A (20), Orlowski R (21).
The International Myeloma Working Group consensus updates the definition for high-risk multiple myeloma based on cytogenetics Several cytogenetic abnormalities such as t(4;14), del(17/17p), t(14;16), t(14;20), non-hyperdiploidy and gain(1q) were identified that confer poor prognosis.
The prognosis of patients showing these abnormalities may vary with the choice of therapy. Treatment strategies that have shown promise for high risk cytogenetic diseases, such as proteasome inhibitor in combination with lenalidomide/pomalidomide, double autologous stem cell transplant plus bortezomib, or combination of immunotherapy with lenalidomide or pomalidomide.
Careful analysis of cytogenetic subgroups in trials comparing different treatments remains an important goal. Cross trial comparisons may provide insight in the effect of new drugs in patients with cytogenetic abnormalities. However, in order to achieve this, consensus on definitions of analytical techniques, proportion of abnormal cells and treatment regimens is needed.
Based on data available today, bortezomib and carfilzomib treatment appear to improve complete response, progression-free survival and overall survival in t(4;14) and del(17/17p), while lenalidomide may be associated with improved progression-free survival in t(4;14) and del(17/17p). Patients with multiple adverse cytogenetic abnormalities do not benefit from these agents. FISH data are implemented in the revised International Staging System for risk stratification.
CITATION Blood. 2016 Mar 21. pii: blood-2016-01-631200