Program: Oral and Poster Abstracts
Session: 653. Myeloma: Therapy, excluding Transplantation: Poster I
We sought to analyse the line of therapy in RRMM after Pom-Dex treatment, the response to further treatment line and survival post pomalidomide era.
Methods. We included 134 patients from the 2 IFM studies (IFM2009-02 in end stage RRMM, n=84, median therapy 5 lines and IFM2010-02 in del17p and/or t(4;14) RRMM, n=50, median therapy 2 lines) treated with Pom-Dex. In both studies, patients received pomalidomide (oral 4mg daily) given either 21 days out of 28 or continuous and dexamethasone (oral 40mg weekly, but 20mg if >75 years old in the IFM 2010-02), given until progression. Overall, 95/135 patients (70%) received further therapy post Pom-Dex, 57/84 (68%) and 38/50 (76%) in IFM2009-02 and IFM2010-02 studies, respectively; the remaining patients had palliative care.
Results. As a whole for the 95 patients, the median age was 60 (range 31-82), the M/F ratio was 1.5, t(4;14) was observed in 26/50 (52%) and del17p in 14/47 (30%). The post Pom-Dex regimens were very diverse, and varied significantly across the 2 trials; however, the regimens contained alkylating agents in 54% and 60% of patients in IFM2009-02 and IFM2010-02, respectively. The most prescribed alkylator was cyclophosphamide (60%) in IFM2010-02 while similar prescription of cyclophosphamide and bendamustine was observed in about 40% of patients in the IFM2009-02 study (p=0.032). Alkylating agents were administered primarily in a 3 drugs-based combination (or more) in IFM2010-02, 70%, versus in combination solely to dexamethasone for most patients in IFM2009-02, 60% (p=0.034). Amongst the combinations of alkylating agents, novel agents were considered in 55% versus 17.5% in the 2 studies, as expected considering that IFM2010-02 included patients exposed but not refractory to lenalidomide, while IFM2009-02 recruited essentially patients double refractory to lenalidomide and bortezomib (p<0.0001). Interestingly, in 57% of cases the novel agent used was bortezomib, often associated to thalidomide.
When no alkylating agent was used, bortezomib plus dexamethasone, dexamethasone alone, or clinical trials were favoured, the latter in a lesser instance. An intensification was proposed in 8% of patients (n=8), with allogeneic transplantation in 3 patients.
27% and 29% responded to the post Pom-Dex regimen, with an extra 35% and 34% having stable disease in the 2 studies, respectively.
With a median follow-up of 49 months (IFM2009-02) and 24 months (IFM2010-02), 77% and 52% of patients have died. The median PFS on Pom-Dex was approximately 5 months (CI95% 2.5;6.5) across the studies, with 20% of patients free of relapse beyond a year, similar to the post Pom-Dex phase, 5 months (2.9;7.0) and 4 months (2.2;5.7) in 2010-02 and 2009-02, with 29% and 13% of patients progression-free beyond one year, respectively.
Importantly, the median OS of IFM2009-02 study (end stage RRMM, median 5 lines) for patients that had a post pomalidomide regimen was 20 months (14;26), with 30% of patients beyond 3 years, versus 13 months for the study as a whole (Leleu et al. Blood 2013) including patients considered in palliative care after Pom-Dex was stopped. This difference was not observed in IFM2010-02 to the same extent, in patients treated earlier with Pom-Dex but characterized with poor risk cytogenetic features, del17p and/or t(4;14), median OS of 14 months (9;18) across the 2 subgroups versus a median OS of 12 months and 9.8 months for the 2 subgroups in the study as a whole (Leleu et al. Blood 2015).
Conclusion. Pom-Dex changed the paradigm in advanced RRMM with a prolonged PFS that translated into a prolonged OS. Importantly, OS was further improved when patients were offered a post pomalidomide therapy particularly in advanced RRMM with no poor risk cytogenetic features. Future studies might confirm the survival impact of pomalidomide used earlier in the disease course.
The IFM2009-02 and 2010-02 trials were conducted with the support of Celgene
Disclosures: Karlin: BMS: Honoraria ; Janssen: Honoraria ; Amgen: Honoraria ; Sandoz: Honoraria , Membership on an entity’s Board of Directors or advisory committees ; Celgene: Honoraria . MACRO: celgene: Membership on an entity’s Board of Directors or advisory committees ; jansen: Membership on an entity’s Board of Directors or advisory committees ; millenium: Membership on an entity’s Board of Directors or advisory committees . Arnulf: Celgene: Membership on an entity’s Board of Directors or advisory committees ; Janssen: Membership on an entity’s Board of Directors or advisory committees . Stoppa: Amgen: Consultancy , Honoraria ; Celgene: Consultancy , Honoraria , Research Funding ; Novartis: Consultancy , Honoraria ; Janssen: Consultancy , Honoraria . Legros: BMS: Speakers Bureau ; Novartis: Research Funding , Speakers Bureau ; ARIAD: Speakers Bureau . Garderet: Bristol-Myers Squibb: Consultancy . Moreau: Celgene: Honoraria , Membership on an entity’s Board of Directors or advisory committees ; Janssen-Cilag: Honoraria , Membership on an entity’s Board of Directors or advisory committees ; Millennium: Honoraria , Membership on an entity’s Board of Directors or advisory committees ; Novartis: Honoraria , Membership on an entity’s Board of Directors or advisory committees ; Bristol-Myers Squibb: Honoraria , Membership on an entity’s Board of Directors or advisory committees . Avet-Loiseau: Janssen: Research Funding ; Celgene: Research Funding ; Takeda: Research Funding . Attal: jansen: Honoraria ; celgene: Membership on an entity’s Board of Directors or advisory committees . Facon: Janssen: Membership on an entity’s Board of Directors or advisory committees , Speakers Bureau ; Celgene: Membership on an entity’s Board of Directors or advisory committees , Speakers Bureau ; BMS: Membership on an entity’s Board of Directors or advisory committees ; Onyx: Membership on an entity’s Board of Directors or advisory committees ; Millenium: Membership on an entity’s Board of Directors or advisory committees ; Novartis: Membership on an entity’s Board of Directors or advisory committees ; Amgen: Membership on an entity’s Board of Directors or advisory committees ; Pierre Fabre: Membership on an entity’s Board of Directors or advisory committees . Leleu: Pierre Fabre: Honoraria ; BMS: Honoraria ; Novartis: Honoraria ; TEVA: Honoraria ; Amgen: Honoraria ; Takeda: Honoraria ; Celgene: Honoraria ; Janssen: Honoraria ; LeoPharma: Honoraria ; Chugai: Honoraria .
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