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ASCO 2012: Dr. Papanikolaou - Metronomic therapy for heavily pretreated relapsed/refractory multiple myeloma (RRMM)

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Xenofon Papanikolaou, MD
Myeloma Institute for Research and Therapy
Little Rock, Arkansas, USA
06.26.12

Poster Discussion Abstract 8041

Author(s):
Xenofon Papanikolaou, Jackie Szymonifka, Alan Mitchell, Jason Keller, Christoph Johann Heuck, Sarah Waheed, Saad Zafar Usmani, Bijay Nair, Frits Van Rhee, Stephen Charles Medlin, Clyde Bailey, Nathan Petty, Antje Hoering, John Crowley, Bart Barlogie; Myeloma Institute for Research and Therapy, Little Rock, AR; Cancer Research and Biostatistics, Seattle, WA

ABSTRACT

Background:
RRMM represents a true challenge in MM therapy. Based on the effectiveness of metronomic therapy in solid tumors, we developed a treatment of metronomically scheduled therapy (MT) for RRMM (Hollmig, ASH 2004). We are now updating our experience with a median follow up of 25.6 months.

Methods:
We identified 187 patients treated with MT from 03/2004 to 11/2011.

Results:
The median age was 61 years (range 36-83); the median number of prior therapies was 14 (range 1-51). 79% of patients had prior HDT, 99% had a prior exposure to bortezomib, 98% to an IMiD, and 95% to their combination . The median number of completed MT cycles was 1 (range 1-5). 63% of patients had a response of MR or better (6% CR ,7% VGPR, 36% PR, 16% MR). The median overall (OS) and progression free (PFS) survivals were 11.3 and 3.7 months respectively. 91 of 187 patients had gene expression profiling (GEP) prior to initiation of MT, of which 53% were high risk according to the 70-gene (GEP70) risk model. OS was affected by elevated CRP (> 8mg/L, HR=1.71, p=0.009) and cytogenetic abnormalities within 6 months of initiation of MT (HR=2.45, p<0.001). For the 91 patients with GEP data available, OS was correlated with elevated CRP > 8mg/L (HR=2.11, p=0.009) and GEP70 high-risk (HR=2.65, p<0.001), which also showed a trend towards shorter PFS. Hematological toxicity grading was difficult as 69% of patients presented with grade >=3 thrombocytopenia within 90 days prior to starting MT. Grade 4 leucopenia , anemia thrombocytopenia due to MT occurred in 74%, 17%, 89% of patients respectively. Incidence of grade 4 neutropenic fever was 1%. Grade 4 or worse incidence of all non-hematological toxicities was below 9%. Most patients were treated in the outpatient setting (95%) and secondary admissions due to regimen toxicity occurred in 20%.

Conclusions:
MT is an effective salvage treatment in RRMM, with a high ORR and a favorable toxicity profile.


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