Gain of Chromosome 1q Portends Worse Prognosis in Multiple Myeloma Patients with Treated with Novel Agent Based Induction Regimens Even after Autologous Transplantation

Background: Gain of chromosome 1q (+1q) is a frequent abnormality that has been associated with resistance to treatment and shorter survival in MM. We describe the impact of autologous transplantation (auto) on survival after treatment with novel agent based induction regimens.

Methods:  We identified 135 newly diagnosed symptomatic MM patients who had FISH performed on pre-treatment bone marrow specimens at our institution between 1/2009 and 12/2012. Standard karyotype and FISH were performed as previously described (Gerritsen et al. Blood 1992), and the copy number and percentage of cells involved was collected. Progression free survival (PFS) and overall survival (OS) were calculated based on IMWG criteria from diagnosis and transplant and estimated by Kaplan-Meier A log-rank test was used to compare survival based on +1q, and Cox proportional-hazards regression was used to further adjust for standard MM risk factors.

Results: 25/135 (19%) had +1q.  Median age was 60 with the majority of patients being male (76% in with+1q vs 57% without, p=0.112) and Caucasian (76 vs 73%). Median follow-up was 3.2 years (yrs) (range 0.13-5.5). When compared to patients without +1q, 40 vs 49% had International Staging System (ISS) Stage I disease, while 28 vs 25% had Stage II, and 32 vs 26% had Stage III (p=0.63). Complex karyotype was seen in 52% with +1q vs 15% without (p=0.002).  64 vs 43% (p=0.075) had extramedullary disease and 96 vs 78% (p=0.045) had lytic lesions at diagnosis. Copy number of +1q ranged from 3-5 with a median of 17% of cells involved (range 2-98%). Induction regimens included combination lenalidomide(R), bortezomib (V), cyclophosphamide (C), & dexamethasone (D), with 31% receiving RD, 12% VD, 30% RVD, and 16% VCD. Best response to induction was >very good partial response in 40 vs 54% (p=0.27).  80 vs 68% underwent auto, and 32 vs 5% both auto and allo. Median PFS was 2.13 years (1.71- not reached (NR)) with +1q vs 3.87 years (3.21- NR) without (Figure 1), while median OS was 4.4 years (2.93-NR) with +1q and was not reached in those without (Figure 2). After an auto, median PFS and OS were lower with +1q (p=0.006, p=0.006) (Figure 3). On univariate and multivariate analysis, +1q and ISS stage were significantly associated with worse PFS. For OS, both ISS and +1q were significant on univariate, but only ISS on multivariate analysis.

Conclusion:  Patients were more likely to have complex karyotypes and lytic lesions at diagnosis. Response to novel agent induction regimens was high and similar in both groups. Overall, gain of 1q portends worse PFS and OS which is not negated by auto transplant.

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