Complex karyotype in patients with mantle cell lymphoma predicts inferior survival and poor response to intensive induction therapy.
BACKGROUND
Risk stratification of newly diagnosed patients with mantle cell lymphoma (MCL) primarily is based on the MCL International Prognostic Index (MIPI) and Ki-67 proliferative index. Single-center studies have reported inferior outcomes in patients with a complex karyotype (CK), but this remains an area of controversy.


METHODS
The authors retrospectively reviewed 483 patients from 5 academic centers in the United States and described the effect of a CK on survival outcomes in individuals with MCL.


RESULTS
A CK was found to be associated with inferior overall survival (OS) (4.5 vs 11.6 years; P<.01) and progression-free survival (PFS) (1.9 vs 4.4 years; P<.01). In patients who underwent high-intensity induction followed by autologous stem cell transplantation (ASCT) in first remission, a CK was associated with poor OS (5.1 vs 11.6 years; P = .04) and PFS (3.6 vs 7.8 years; P<.01). Among patients with a CK, high-intensity induction had no effect on OS (4.5 vs 3.8 years; P = .77) nor PFS (2.3 vs 1.5 years; P = .46). Similarly, ASCT in first remission did not improve PFS (3.5 vs 1.2 years; P = .12) nor OS (5.1 vs 4.0 years; P = .27). On multivariable analyses with Ki-67 and MIPI, only CK was found to be predictive of OS (hazard ratio [HR], 1.98; 95% confidence interval [95% CI], 1.12-3.49 [P = .02]), whereas both CK (HR, 1.91; 95% CI, 1.17-3.12 [P = .01]) and Ki-67 >30% (HR, 1.86; 95% CI, 1.06-3.28 [P = .03]) were associated with inferior PFS. Multivariable analysis did not identify any specific cytogenetic abnormalities associated with inferior survival.


CONCLUSIONS
CK appears to be independently associated with inferior outcomes in patients with MCL regardless of the intensity of induction therapy and receipt of ASCT. Cytogenetics should be incorporated into the workup of a new diagnosis of MCL and novel therapeutic approaches should be investigated for patients with CK. Cancer 2018;124:2306-15. © 2018 American Cancer Society.
['Greenwell|I Brian|IB|0000-0003-2752-8078', 'Staton|Ashley D|AD|', 'Lee|Michael J|MJ|', 'Switchenko|Jeffrey M|JM|', 'Saxe|Debra F|DF|', 'Maly|Joseph J|JJ|', 'Blum|Kristie A|KA|', 'Grover|Natalie S|NS|', 'Mathews|Stephanie P|SP|', 'Gordon|Max J|MJ|', 'Danilov|Alexey V|AV|', 'Epperla|Narendranath|N|0000-0002-8216-3457', 'Fenske|Timothy S|TS|', 'Hamadani|Mehdi|M|0000-0001-5372-510X', 'Park|Steven I|SI|', 'Flowers|Christopher R|CR|0000-0002-9524-3990', 'Cohen|Jonathon B|JB|']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D000971:Antineoplastic Combined Chemotherapy Protocols D002869:Chromosome Aberrations D003131:Combined Modality Therapy D005260:Female D005500:Follow-Up Studies D005820:Genetic Testing D018380:Hematopoietic Stem Cell Transplantation D006801:Humans D059785:Karyotype D007621:Karyotyping D019394:Ki-67 Antigen D020522:Lymphoma, Mantle-Cell D008297:Male D008875:Middle Aged D011237:Predictive Value of Tests D011379:Prognosis D000077982:Progression-Free Survival D012074:Remission Induction D012189:Retrospective Studies D018570:Risk Assessment D014182:Transplantation, Autologous D014481:United States
complex karyotype mantle cell lymphoma (MCL) cytogenetics chemotherapy prognostic markers