High-risk cytogenetic abnormalities in multiple myeloma: PETHEMA-GEM experience

Area of Science:

• Hematology
• Oncology
• Genetics

Background:

• Multiple myeloma (MM) is a hematologic malignancy characterized by genetic complexity.
• Cytogenetic abnormalities play a crucial role in MM pathogenesis and patient prognosis.
• Understanding the impact of specific genetic alterations and their co-segregation is vital for accurate risk stratification.

Purpose of the Study:

• To investigate the prognostic significance of individual and co-segregating cytogenetic abnormalities in newly diagnosed multiple myeloma (MM) patients.
• To evaluate the impact of specific genetic alterations, including t(4;14), t(14;16), del(17p), +1q, and del(1p), on progression-free survival (PFS) and overall survival (OS).

Main Methods:

• Analysis of 1304 newly diagnosed MM patients from four GEM-PETHEMA clinical trials.
• Fluorescence in situ hybridization (FISH) was used to detect genetic alterations in CD38 purified plasma cells.
• Statistical analysis was performed to assess the impact of cytogenetic abnormalities and their co-segregation on PFS and OS.

Main Results:

• The study identified frequencies of del(17p) (8%), t(4;14) (12%), t(14;16) (3%), +1q (43%), and del(1p) (8%).
• t(4;14) and gain(1q) were associated with shorter PFS and OS. Del(17p) showed poor prognosis with a cut-off of ≥20% positive cells.
• Co-segregation of abnormalities worsened prognosis in t(4;14) patients, while del(17p) retained its adverse effect independently. The detrimental effect of +1q or del(1p) was diminished when co-segregation was excluded.

Conclusions:

• High-risk cytogenetic abnormalities are confirmed as significant prognostic factors in MM.
• The co-occurrence of cytogenetic abnormalities significantly influences MM patient outcomes.
• Accurate prognosis assessment in MM requires consideration of both individual genetic alterations and their co-segregation patterns.