Gene expression profiling (GEP) in multiple myeloma (MM): Distinguishing relapses with high-risk transformation from those with sustained low risk.

Abstract

8122 Background: GEP-defined high-risk identifies ∼15% of untreated patients with a dismal outcome. Among the 85% with low-risk MM, high-risk transformation can be observed at the time of relapse. The purpose of this investigation was to determine whether, among patients relapsing on Total Therapy 2 (TT2) and TT3, baseline features existed that could distinguish patients with sustained low-risk (LOLO) from those with high-risk progression (LOHI) versus those with HIHI. Methods: Of 351 TT2 and 510 TT3 patients with baseline (BL) GEP information, a total of 237 have relapsed with relapse GEP available in 127. We are reporting here on the frequency of LOHI transformation relevant to baseline characteristics and treatment details (TT2 control v thalidomide arm, TT3), timeliness of completion of therapy (CT), duration of disease control antedating relapse (DDC). Results: From our MM data base, we identified 60 LOLO, 26 LOHI and 34 HIHI. Distinguishing BL GEP features included higher median GEP risk score (RS) values in HIHI (1.136) v LOHI (0.289) v LOLO (-0.270) (p<0.001); delTP53 was more prevalent in HIHI (27%) v LOHI (8%) v LOLO (7%) (p=0.017); concomitancy of amp1q21/del1p was more frequent in HIHI (36%) than LOHI (17%) than LOLO (9%) (p=0.005). Among non-GEP BL parameters, CA-13/CA- hypo, high LDH (≥300 and ≥ 500 U/L), low albumin (<3.5 g/dL) and high B2M (> 5.5 mg/L) also were significantly more common in HIHI than LOHI and LOLO. Applying logistic regression, LOLO could be distinguished from LOHI by the presence metaphase cytogenetic abnormalities (CA) of the del13 variety (CA13; OR=0.37, p=0.055). Conclusions: Although HIHI is readily distinguishable from LOHI and LOLO by several baseline parameters, the absence of CA13 was the only baseline variable with near-significance in predicting, in low-risk myeloma, low- from high-risk relapse, attesting to the far- reaching power of metaphase karyotyping. No significant financial relationships to disclose.