PF770 OUTCOMES FOR MELPHALAN‐VELCADE BASED AUTOGRAFT IN HIGH RISK MULTIPLE MYELOMA PATIENTS: A SINGLE‐CENTRE EXPERIENCE
Authors: D. Routledge, T. Joyce, C. Wood, S. Harrison
Journal: HemaSphere (2019)

Background: Despite the accepted utility of autologous stem cell (AuSCT) transplantation for multiple myeloma, the outcomes for ‘High Risk’ patients remain poor. Based on the original French study reports it has been our practice to add velcade to the melphalan conditioning in this difficult patient group to improve outcomes. However, the recent Phase 3 trial by the IFM Network did not show any benefit of this regime in high‐risk patients (ISS Stage III, del17p or t(4;14) and response rate PR or worse). Here we report our single‐centre experience of high risk myeloma patients who underwent Melphalan‐Velcade (Mel‐Vel) AuSCT. Aims: To assess the reponse rates of patients undergoing Mel‐Vel AuSCT for high risk multiple myeloma compared to an historical cohort of Mel AuSCT patients at our centre Methods: A retrospective case note audit identified 54 patients undergoing Mel‐Vel AuSCT for high risk multiple myeloma between 2009 and 2018 at the Clinical Haematology Department of Peter MacCallum and Royal Melbourne Hospital, Australia. An historical cohort of 83 high risk melphalan only AuSCT were also identified as a comparator arm. High risk patients were defined by the presence of ISS Stage III disease, an adverse cytogenetic marker or those undergoing a second AuSCT. Results: Median age at transplant was 62 years (range 40 to 79 years). 61% of patients were male (n = 33) and 39% female (n = 21). 29 patients had IgG Myeloma (54%), 14 IgA Myeloma (26%), 1 patient IgM Myeloma (2%) and 10 had light chain myeloma (18%). High risk features included 12 patients with ISS Stage III Disease (22%), 28 a high risk cytogenetic abnormality (52%), 32 had undergone &gt;1 Autograft (59%), 1 had early progression (2%). Additionally, 33% of patients had &gt;1 high risk feature present (n = 18). 39% received an iMiD (n = 21), 61% a Proteasome Inhibitor (n = 33) and 20% PACE based chemotherapy (n = 11) as part of their induction regime. 23 of these patients had not previously undergone an autograft, 27 a previous autograft and 4 patients had 2 previous autografts. 3 patients received a tandem autograft. Responses post induction were sCR = 1 (2%), VGPR = 8 (15%), PR = 27 (44%), SD = 4 (7%) and PD = 14 (25%). Conditioning regimes included Melphalan ≤140 mg/m2+Velcade (n = 19; 35%) and Melphalan &gt;140 mg/m2+Velcade (n = 35; 65%). Velcade was given at a dose of 1.3 mg/m2 on D‐1 and D+2. Median stem cell dose was 4.14 x 106/kg. Median time to neutrophil engraftment and platelet engraftment was 11 and 12 days respectively. 7 patients received consolidation chemotherapy and 24 underwent maintenance therapy. Responses at 3 months post autograft were sCR = 4 (7%), CR = 7 (13%), VGPR = 9 (17%), PR = 9 (17%), SD = 1 (2%), PD = 11 (20%) and 3 died during autograft (6%). Median PFS post AuSCT was 15 months (range 0 to 88) and Median OS was 30 months (range 0 to 112). Of the 183 high risk patients identified in the historical comparator Melphalan only arm 83 had high risk features including poor response (&lt;PR: n = 13; 16%), Stage III disease (n = 15; 18%) and adverse cytogenetics (n = 55; 66%). Of those who had a response assessment done at 3 months 29 had achieved ≥VGPR (34%). Summary/Conclusion: Use of Melphalan‐Vel conditioning did not improve response rates at 3 months compared to the comparator Melphalan only arm (≥VGPR = 37% vs 34%) in keeping with the results from the IFM trial. However caution should be expressed in directly comparing patient groups due to different induction regimes, high risk features, multiple AuSCT, as well as variable consolidation and maintenance regimens in this patient cohort.