Metaphase Cytogenetic Abnormalities (M-CA) and Interphase FISH for Deletion 13 (FISH 13) in Total Therapy 2 (TT 2): Follow up Observation among? 380 Patients with Newly Diagnosed Multiple Myeloma (MM).

We have previously reported on the adverse prognostic implications m-CA, present in ~ 33% of newly diagnosed patients especially when involving del 13 (~ 20%). To overcome the proliferation dependency of m-CA, FISH has been applied detecting abnormalities in virtually all patients with MM; FISH 13, detected in ~ 50% has been associated with poor outcome with both standard and high dose therapies. Of a total of 668 patients accrued to Total Therapy 2, 380 had baseline evaluations for m-CA and FISH 13. We examined 2 different cut-points of FISH 13 deletion, the traditional ≥ 20% (FISH 13–20) and an 80% cut-off (FISH 13–80). In case of FISH 13–20, major differences in both EFS and OS were noted among those exhibiting CA, with an adverse effect of FISH 13–20, whereas there was no difference among the majority of patients exhibiting no CA (Figure 1). However, using FISH 13–80, adverse effects of FISH 13 were observed for both no CA and CA subgroups (FISH 2). Indeed, 4-yr estimates of EFS/OS were highest at 73%/85% among 204 patients in the no CA/FISH 13–80-negative group compared to 54%/69% among the 42 with no CA and FISH 13–80-positive group. Similarly, among 134 patients with CA, those with FISH 13–80-positive disease had 4-yr EFS/OS of only 23%/22% compared 44%/58% among the 103 without FISH 13–80. Our data confirm the overriding importance of m-CA for prognosis and, in addition, reveal the importance of the proportion of plasma cells revealing del 13 as an additional key parameter in both no CA and CA subgroups. Biologically, these data would suggest a marked clinically relevant heterogeneity of FISH 13 that deserves further evaluation.