Newly Diagnosed Myeloma (MM) Patients (Pts) with High-Risk (HR) Cytogenetics By FISH: Is There a Role for Tandem Autologous Stem Cell Transplantation (ASCT)?
Authors: Farshchi-Zarabi Sara , Parmar Gurdeep , Masih-Khan Esther , Farooki Sophia , Chen Christine , Kukreti Vishal , Prica Anca , Tiedemann Rodger , Trudel Suzanne , Reece Donna 
Published: October 2019

Abstract
Background: Recent analyses have suggested that newly diagnosed multiple myeloma (MM) patients with the high-risk (HR) chromosomal abnormalities del 17p and t(4;14) detected by FISH may benefit from bortezomib (BTZ)-based induction therapy and tandem autologous stem cell transplantation (ASCT) (Sonneveld P et al, J Clin Oncol 2013;31: 3279). At Princess Margaret Cancer Centre, we have offered upfront tandem ASCT for HR pts with del 17p, t(4;14) and/or t(14;16) and now retrospectively review the results of this approach.
Methods: After obtaining Institutional Research Ethics Board approval, we used Princess Margaret Myeloma Database to identify HR MM pts who underwent tandem ASCT between June 2005 and January 2015. We performed a retrospective chart review to investigate the survival outcome of this group of patients.
Results: Between 06/05 and 01/15, 52 HR pts underwent tandem ASCT at Princess Margaret Cancer Centre. 21 had del 17p, 20 had t(4;14), 5 had t(14;16), 3 had both t(4;14) + del 17p and 3 had both t(14;16) + del 17p. Median age was 56.5 yrs (range 31-71); 34 were male. ISS stage was I in 12, II in 15, III in 12 and N/A in 13 pts. The majority (42 pts) received BTZ-based induction therapy which consisted of CyBorD in 38; 11 pts required a 2nd regimen before ASCT. The median time from diagnosis to 1st ASCT was 6.7 mos (range 4.8 -45.7) and the median time between transplants was 3.7 mos (range 0.9- 6.6); 30 pts received lenalidomide (len) between ASCTs to prevent early relapse. All but 2 pts (96%) received maintenance therapy after the 2nd ASCT which included thalidomide in 7 (13%), len +/- steroids in 39 (75%) and BTZ +/- len in 4 (8%) of all pts. Thirty-six (69%) received both BTZ-based induction and len maintenance after the 2nd ASCT. No transplant-related deaths occurred. Median follow-up is 26.3 mos (range 9.1 to 104.3).
The median overall survival in all 52 pts from diagnosis was 31.1 mos (range 11.9 to 110.8) with a median PFS of 24.0 mos (9.1 to 83.6); median survival after progression was only 8.2 mos (0.1-62.8) mos in the 16 pts who relapsed after the 2nd ASCT.Table 1.HR Group#Calculated from diagnosisCalculated from 2nd ASCTMedian PFS, mos (range)Median OS, mos (range)Median PFS, mos (range)Median OS, mos (range)t(4;14)2322.4 (11.4-58.1)29.9 (17.7-84.4)7.0 (0.2-23.5)17.3 (5.4-73.6)Del 17p2724.4 (9.1-83.6)35.0 (11.9-110.8)11.2 (1.3-69.4)25.3 (3.8-99.6)t(14;16)827.4 (10.3-55.4)30.6 (11.9-55.4)16.9 (2.2-48.1)19.7 (3.8-48.1)Both BTZ-induction + len maint3622.2 (10.3-55.4)30.5 (11.9-67.5)8.1 (1.4-48.1)18.7 (3.8-57)No BTZ-induction + len maint1627.2 (9.1-83.6)49.5 (22.0-110.8)12.1 (0.2-69.4)24.5 (6.9-99.6)
Conclusions: 1) MM pts with HR cytogenetics, particularly those with t(4;14), have a short PFS and OS after tandem ASCT; 2) even following BTZ-based induction therapy and len maintenance, outcomes with tandem ASCT are suboptimal in HR pts; 3) further investigations are necessary to identify novel strategies for the management of HR MM in the era of modern therapeutic agents.

Disclosures
Chen: Celgene: Consultancy, Honoraria, Research Funding. Kukreti:Janssen Ortho: Honoraria; Roche: Honoraria; Lundbeck: Honoraria; Amgen: Honoraria; Celgene: Honoraria. Tiedemann:Janssen Ortho: Honoraria; Celgene: Honoraria; Amgen: Honoraria. Trudel:Oncoethix: Research Funding; Novartis: Honoraria; Trillium Therapeutics Inc.: Research Funding; BMS: Honoraria; Amgen: Honoraria, Speakers Bureau; Celgene: Equity Ownership, Honoraria, Speakers Bureau. Reece:Lundbeck: Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Otsuka: Research Funding; Merck: Research Funding; Millennium Takeda: Research Funding; Bristol-Myers Squibb: Research Funding; Amgen: Honoraria; Onyx: Consultancy; Janssen-Cilag: Consultancy, Honoraria, Research Funding.