ALBERT

Description: Abstract 3951 Aim: The aims of this study were on one hand, to evaluate the significance of achieving molecular response (MR) by fluorescent-PCR (F-PCR) of Ig genes in a prospective way, particularly in patients with singular cytogenetics' features. On the other hand, to compared MR with immunophenotypic response (IR) and complete remission by immunofixation (CR). Patients: 130 new MM patients who had achieved CR or VGPR were analyzed by PCR, multiparametric flow cytometry (MFC) and immunofixation at diagnosis, and after induction therapy or transplantation: 48 patients received conventional chemotherapy as induction therapy followed with ASCT and were included in the GEM2000 trial and the other 82 patients were enrolled in the GEM2005 clinical trials in which the induction and maintenance therapy were based on Bortezomib and/or Thalidomide. Methods: The molecular analysis of Immunoglobulin (Ig) gene rearrangements at diagnosis was carried out by fluorescent PCR in DNA from bone marrow samples according to the Biomed-2 protocols. Briefly three different multiplex PCRs: DHJ; Ig Kappa light chain (IGK) rearrangements K-VJ and Kappa deleting element (KDE). DHJ and light chain rearrangements detected at the diagnosis were used in the follow-up. The sensitivity of PCR was between 1/103 and 1/104 as Martínez P. et al previously published in BJH, 2008. Regarding MFC the following monoclonal antibody combinations (FITC/PE/PerCP-Cy5.5/APC) were used at the diagnosis to identify different aberrant plasma cells phenotypes which were used as patient-specific probes for Minimal Residual Disease. Results: 64 patients had negative F-PCR and 66 patients had positive F-PCR after induction therapy. The OS was 77.32% and 59.18%, respectively and the medians OS were 116 and 67 months for each group (P= 0.03). Regarding the PFS, 28 of the 64 F-PCR negative patients relapsed while there were 44 relapses in the group of positive F-PCR. The 5y PFS was 56.44% and 27.43% respectively; the medians PFS were 60 and 36 months respectively (P= 0.0005). The multivariate analysis showed that achieving molecular response by F-PCR had a independent prognostic value in PFS (P=0.003, HR 2.3). Interestingly amongst patients who achieved CR, F-PCR identified a population of patient with a better PFS, figure A (P= 0.04, HR 2.179).The applicability of the F-PCR was almost equivalent to that observed by MFC (91.5 vs. 92%). Nevertheless we found discordant results between these two response criteria. Approximately the 20% of patients who had achieved a MR no obtained IR. The opposite pattern also was observed (IR/noMR) in 10% of the patients. In order to see if the PCR showed differences in terms of survival in patients with high or low risk cytogenetics features at the diagnosis, we made two independent analysis: in one hand we analyzed 14 patients with high-risk cytogenetics [t(4;14), t(14;16) and/or del(17p)] and on the other hand 72 patients with standard-risk cytogenetics. In the former analysis, 4 of the 8 who had negative F-PCR relapsed after the induction therapy while the totality of the other six with positive F-PCR did. The medians PFS were 32 and 17 months respectively (P= 0.0002). In connection with the 72 patients with standard-risk cytogenetics, 13 of the 34 who had negative F-PCR relapsed while 24 of the 38 with positive F-PCR did. The medians PFS times were 75 and 38 months respectively, figure B (P= 0.01). Conclusion: F-PCR of IgH rearrangements is a simple, cheap and feasible method for evaluating response in MM patients after induction therapy or transplantation. Additionally achieving MR provides a similar prognostic value to IR in patients differentially treated, and particularly in patients with singular cytogenetics' features as well as in patients with CR by immunofixation. Disclosures: Paiva: Jansen-Cillag: Honoraria; Celgene: Honoraria. Rosiñol:Janssen: Honoraria; Celgene: Honoraria. Alegre:Janssen: Honoraria; Celgene: Honoraria. Blade:Centocor Ortho Biotech Research & Development: Research Funding. San Miguel:Janssen-Cilag: Honoraria; Celgene: Honoraria. Lahuerta:Celgene: Honoraria; Janssen: Honoraria.

Description: Aim: To evaluate the efficacy of Lenalidomide (Len) as compassionate use in relapsed or progressive Multiple Myeloma (MM) up to its approval in Spain. Patients and Methods: GEM-PETHEMA designed a transverse and retrospective, multicenter analysis of MM cases which Len compassionate use was requested until December, 2007. The decision to treat these patients was previous and independent from the decision to conduct the present analysis and depended only on the clinical criteria of the responsible doctors. At least, one response assessment was a must for efficacy analysis. Results: 111 MM patients have been included. Eligible patients for efficacy were 103. Mean age was 65.7 (38–85); 53 m, 50 f. Previous median lines of therapy were 3 (1–8): 92 (89.3%) have received bortezomib; 37 (35.9%) autologous PBSCT and 26 (25.2%) thalidomide. Extramedullary plasmocitomas were present in 25 (24.3%). Mean Len dose was 22.8 mg (± 4.9): 82 (79.6%) received the standard dose and schedule (25 mg d for 3 w every 4 w) and 21 (20.4%) received less dose and/or different schedule. 92 (89.3%) received Dexametasone (mean dose 58.33 mg/w) [± 35.8]). Response: 4 (3.9%) sCR, 11 CR (10.7%), 12 VGPR (11.7%), 41 PR (39.8%), 20 SD (19.4%), 13 PD (12.6%), 2 NE (1.9). Among groups, response equal or superior to PR was observed in all settings: 64.1% in prior exposed to bortezomib, 46.1% in prior exposed to thalidomide and 40.0% in patients with extramedullary plasmocitomas. Previous transplant, the number of previous lines received, renal failure, age, or cytogenetic did not affect significantly the overall response rate. Median duration of treatment was 7.7 m (1–21); median TTP was 8.3 m and median global survival since starting Len therapy was 11 m (6–22). Median survival since diagnostic was 49 m (40–60). At the time of analysis, 46 (45.5%) patients were still on Len therapy, and 72 (79.6%) were alive. Toxicity: ≥ grade II: neutropenia, 51 (46.4%); thrombocytopenia, 39 (35.5%); DVT, 5 (4.5%); rash, 3 (2.7%); neutropenic fever, 8 (7.3%); others, 13 (11.8%). DVT/PE prophylaxis was used in 89 (86.4%) patients: LWMH in 43.8 % and low dose aspirin in 48.3 %. No PE was reported. Conclusions: Lenalidomide is effective in this heavily pre-treated MM population-progressive or refractory to standard therapy-even in different clinical settings. The most frequent association to Len was intermediate dose of Dex. Although response rate was superior in patients exposed previously to bortezomib, no differences on duration and survival were observed. Patients with extramedullary plasmocitomas showed also response. Toxicity, mainly myelosupression was predictable and manageable with dose adjustments and cytokine support.