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).
(1) Erasmus MC, Rotterdam, Netherlands
(2) University of Toulouse, Toulouse, France;
(3) Emory University Medical School, Atlanta, GA, United States;
(4) Levine Cancer Institute/Carolinas Healthcare System, Charlotte, NC, United States;
(5) Hackensack University Medical Center, Hackensack, NJ, United States;
(6) Dana-Farber Cancer Institute, Boston, MA, United States;
(7) National University Health System, Singapore;
(8) University Hospital, Nantes, France;
(9) Purpan Hospital, Toulouse, France;
(10) Department of Laboratory Med. and Pathology, Mayo Clinic, MN, United States;
(11) Centre Hospitalier Universitaire de Liege, Liege, Belgium;
(12) University of Heidelberg, Heidelberg, Germany;
(13) Clinica Universitaria de Navarra, CIMA, Pamplona, Spain;
(14) VU University Medical Center Amsterdam, Amsterdam, Netherlands;
(15) Universitaetsklinik Wuerzburg, Wuerzburg, Germany;
(16) Hospital Clinic, IDIBAPS, University of Barcelona, Spain;
(17) International Myeloma Foundation, North Hollywood, CA, United States;
(18) University Hospital Heidelberg and National Center for Tumor Diseases Heidelberg, Heidelberg, Germany;
(19) University of Salamanca, Spain;
(20) University of Torino, Torino, Italy;
(21) MD Anderson Cancer Center, Houston, TX, United States.
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