Autologous Stem Cell Transplant Has a Role In Consolidating Chemotherapy Given At First Disease Progression In Multiple Myeloma Treated Exclusively With Novel Agents
Authors: Kishore Bhuvan , Paneesha Shankaranarayana , Bokhari Syed W , Pillai Shrinivas , Sangha Jason , Nagra Sandeep , Nikolousis Emmanouil , Eden Dewi Tomos , Crowther Mark , Mahendra Prem , Ewing Joanne , Pratt Guy , Smith Neil , Murthy Vidhya , Gardner Clare , Lovell Richard , Karunanithi Kamaraj , Chasty Richard Christopher , Yarwood Karen , Bratby Lynn , Holder Kathy , Lynda Baker , Suhr Julie , Nicolson Pip , Cook Mark 
Published: October 2019

Abstract

Introduction
Up-front autologous stem cell transplantation (ASCT-1) post front line therapy with novel agents is standard of care in newly diagnosed multiple myeloma. The role for salvage transplantation (ASCT-2) in relapsed patients after retreatment remains unclear in the era of the novel agents. Majority of published studies include patients treated in pre-thalidomide era. Our retrospective study investigates the safety and efficacy of ASCT-2 in patients exclusively treated with novel drugs both at upfront and at relapse. Primary end point was non relapse mortality (NRM) at day 100. Secondary end points were progression free survival from ASCT-2 (PFS-2) and overall survival (OS)

Patients and Methods
Thirty-nine patients (21 female and 18 male) underwent ASCT-2 at 4 centres between 2008 and 2013. At initial presentation all received thalidomide based treatments pre ASCT-1. Therapy at progression was bortezomib based in 92% and thalidomide in 8%. Melphalan 200 mg/m2 was used as conditioning for 90% of patients, 140 mg/m2 in 10%. OS and PFS-2 were calculated from ASCT-2. Statistical analysis was carried out using IBM SPSS 19 for Windows.

Results
Median progression free survival (PFS-1) post ASCT-1 was 35 (10-90) months with 4 patients receiving thalidomide maintenance. Median age at ASCT-2 was 60 (37-68) years with a median stem cell dose of 2.7×106 (2-7) CD34 cells /kg body weight. All patients engrafted with median times to neutrophil (>0.5) and platelet (>20) engraftment of 12 days each with a day+100 and 1 year NRM of 0%. With a median follow up from ASCT-2 of 18 (3-52) months, the median PFS-2 was 18 (12-24) months and OS was 42 (33-50) months. PFS-1 of greater than 18 months was associated with prolonged PFS-2 (19 vs. 6 months, p=0.001, log rank), however there was no statistical difference observed for PFS-1 beyond 24 months. Similarly PFS-1 >18 months predicted for improved OS (39 vs. 14 months, p=0.007, log rank). Age at ASCT-2(>or <60yrs) had no impact on PFS-2 or OS. Patient age>60 and with PFS-1 of >24 months had a median PFS-2 of 25months as compared to 14 months in patient age <60 with a PFS-1 of >24 months.

Conclusion
In the era of novel agents ASCT-2 can be safely delivered with 0% 1 year NRM. PFS-1 greater than 18 months gives better PFS-2 and OS suggesting a definite role of this therapy in a selected population Age greater than 60 years does not have adverse impact on either PFS or OS. Thus ASCT-2 should be considered in treatment strategies at disease progression and warrants further prospective studies

Disclosures:
No relevant conflicts of interest to declare.