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As therapy for MM improves, methods more sensitive than conventional serum/urine electrophoresis/immunofixation are required to optimally evaluate response. Our phase 2 multi-center clinical trial, conducted in 10 Canadian centers, utilized serial bone marrow aspirate (BMA) samples for MRD analysis by 8-color multiparameter flow cytometry (MFC), along with serum Hevylite assay of the involved heavy light chains (HLC), to assess responses after ASCT and during maintenance therapy. After btz-based induction therapy (usually CyBorD), pts without progression received enhanced conditioning with BuMel (IV busulfan 3.2 mg/kg days -5 to -3 or days -6 to -4 + melphalan 140 mg/m2 day -2 or day -3) followed by ASCT on day 0. On day 100 post-ASCT, lenalidomide (len) 10 mg/day was commenced, escalated to 15 mg/day after 3 cycles if appropriate, and continued until progression. BMA and serum samples were shipped centrally for MRD and Hevylite analysis before induction therapy, before ASCT, on day 100 post-ASCT, every 3 mos for the 1st year and every 6 mos until progression. From 03/2013 - 07/2015, 122 newly diagnosed pts provided BMA samples for MRD analysis. To date, 70 pts (target 78), have completed induction therapy and undergone ASCT; 8 others provided pre-induction samples and are expected to be enrolled. 44 of the 122 (36%) who provided BMA samples did not proceed to BuMel due to: poor samples-4 pts (3.2%); MM not confirmed-3 pts (2.5%); prior therapy-1 pt (0.8%); death during induction-1 pt (0.8%); consent withdrawal/opted for standard conditioning-19 pts (15.6%); and no ASCT-16 pts (13.1%; 8 were unfit, 4 had comorbidities, 2 progressed, 1 failed mobilization and 1 received tandem ASCT for high-risk MM). Median follow-up is 17.4 mos (range: 6.3-25.6). Median age is 57 (34-69); 64% are male. Median serum β2-microglobulin level is 3.07 mg/L (1.5-20) and albumin 37 g/L (2.8-48.1); 31 pts have ISS stage I; 18 stage II; 15 stage III MM and 6 have missing data. Ig subtype includes IgGκ in 30 (43%), IgGλ in 14 (20%), IgAκ in 8 (12%), IgAλ in 9 (13%), κ in 5 (7%); λ in 1 (1%) and missing data in 3 pts (4%). Post-ASCT, 14 SAEs have occurred: Grade 3 atrial fibrillation (2), acute kidney injury (3), increased creatinine (1), upper respiratory infection (2), febrile neutropenia (2), bacteremia (1), hypoxia (1) and lung infection (1) and Grade 4 sepsis (1). There have been no ASCT-related deaths; 4 pts have progressed. The best conventional Ig response post-induction in the 66 pts with available data is CR in 5 (7.6%), VGPR in 25 (38%), PR in 31 (47%), MR in 4 (6%) and SD in 1 (1.5%). The Ig response at day 100 in the 60 evaluable pts includes CR in 10 (17%), VGPR in 30 (50%), PR in 18 (30%), MR in 1 (1.5%) and SD in 1 (1.5%). MRD negativity improved from 18/67 (27%) after induction to 22/60 (37%) at day 100 (Table 1). Among evaluable pts, 83.3% of those after induction and 68.2% of those at day 100 who were MRD-negative had normal involved HLC ratios, while 42.6% and 51.5% of those who were MRD-positive, respectively, had normal ratios. | | | | MRD Negativity by Conventional Ig Response | | ----------------- | -------------------- | -------------------------------------------------------------------------- | --------------------------------------------- | ----- | | | # Evaluable | Normal Hevylite ratio (# normal /evaluable) (%) | # MRD Negative (%) | CR | VGPR | PR | MR | SD | Missing | | Total | MRD(-) | Total | MRD(-) | Total | MRD(-) | Total | MRD(-) | Total | MRD(-) | Total | MRD(-) | | After Induction | 67 | 15/18 (83.3%) | 18 (27%) | 5 | 4 | 25 | 9 | 31 | 5 | 4 | | 1 | | 1 | | | Day 100 Post-ASCT | 60 | 15/22 (68.2%) | 22 (37%) | 10 | 4 | 30 | 16 | 18 | 2 | 1 | | 1 | | | | Table 1. Response Rates by Conventional Serum/Urine Parameters and Marrow Flow Cytometry for MRD Conclusions : 1) IV BuMel conditioning + ASCT was well-tolerated with few SAEs and no ASCT-related deaths; 2) at day 100 post-ASCT, 97% had achieved ≥ PR (≥ VGPR in 67% and CR in 17%); 3) MRD negativity rates improved from 27% to 37% after ASCT; 3) conventional Ig and MRD responses were often discordant as only 40% of CR pts were MRD-negative at day 100; 4) the majority of MRD-negative patients also had normalization of their involved HLC ratios; 5) further F/U is required to determine the rate of achievement of MRD negativity during maintenance therapy; relationships between conventional Ig response, MRD status and involved HLC ratio; and long-term outcomes with this approach. Disclosures Reece: Janssen: Consultancy, Honoraria, Research Funding; Osuka: Honoraria, Research Funding; Merck: Research Funding; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Millennium: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding. Off Label Use: Lenalidomide maintenance after autologous stem cell transplantation. White: Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Venner: Amgen: Honoraria; Celgene: Honoraria, Research Funding; JJ Janssen: Honoraria; Novartis: Honoraria. Song: Celgene: Honoraria; Otsuka: Honoraria; Janssen: Honoraria. Tay: Celgene: Honoraria; Janssen: Honoraria. Kukreti: Janssen: Honoraria; Celgene: Honoraria. Trudel: Amgen: Honoraria, Speakers Bureau; Oncoethix: Research Funding; BMS: Honoraria; Novartis: Honoraria; Celgene: Equity Ownership, Honoraria, Speakers Bureau; Trillium Therapeutics Inc.: Research Funding. Anca: Janssen: Honoraria; Celgene: Honoraria. Tiedemann: Janssen: Honoraria; Celgene: Honoraria. Chen: Celgene: Honoraria, Research Funding; Millennium: Research Funding; Janssen: Honoraria.