An Outcome Study On Survival and Disease Control in Patients with High-Risk Multiple Myeloma (MM) for Relapse, Treated with High-Dose Melphalan Combined with Bortezomib for Autotransplant Followed by Post-Transplant Maintenance with Bortezomib and Lenalidomide.
Authors: Kee Lee Choon , Kaiser Jeff , Myint Han , Berg Mary , Kolhouse J. Fred , Robinson William 
Published: October 2019

Abstract
Abstract 3404
Poster Board III-292
Long-term survival and disease control following autotransplant have been known to be poor in symptomatic MM patients who were in relapse prior to transplant, had adverse cytogenetic abnormalities (CA) or high LDH (> 190 IU/mL) at diagnosis. In the study, we sought to improve the outcome of these patients by combining bortezomib with standard high-dose melphalan for autotransplant and implementing 3-year post-transplant maintenance with bortezomib, lenalidomide and dexamethasone. Between September 2006 and March 2009, 34 patients (median age 62, range 38 to 77 years) were accrued to the sequential regimens of 1) tandem autotransplant prepared by the MVD of ‘melphalan 200 mg/m2 (D-1) + bortezomib 1.3 mg/m2 × 2 (D-4, D-1) + dexamethasone 20 mg x 4 (D-4 through D-1)’; 2) the VLD of ‘bortezomib 1.3 mg/m2/day x 4 (D1, 4, 8, 11) + lenalidomide 10 mg/day x 14 (D1 through 14) + dexamethasone 20 mg/day x 4 (D1, 4, 8, 11)’ q 3 months for 2 years; 3) the LD of ‘monthly lenalidomide 10 mg/day x 14 + dexamethasone 20 mg q Monday in between of the VLD for the first 2 years, followed by a monthly course for the 3rd year. Of the 34 patients, 11 (32%) had unfavorable CA, 15 (44%) high LDH and 10 (29%) prior relapse. 16 patients (47%) had immunoglobulin (Ig) G, 10 (29%) Ig A, 6 (18%) light chain only and 2 (6%) nonsecretory MM. 14 patients (41%) received tandem transplant and 20 (59%) single transplant due to insurance reasons. 32 patients (94%) were able to maintain the treatment until the last follow-up on August 15, 2009 or until relapse or death. 19 patients achieved either a stringent complete remission (s-CR) (n = 16) or CR (n = 3), with an 1-year cumulative incidence (CI) of 46%. 2 additional patients achieved CR following the 2nd transplant. During the maintenance, 3 additional patients achieved s-CR (N = 1) or CR (n = 2), resulting in 71% of the 18-mo CI of response > CR. By the landmark analysis at the time of transplant, the estimated 3-year Kaplan-Meier survival, CI of relapse and event free survival (EFS) are 96% with 2 deaths (1 of MM, 1 of pulmonary embolism), 15% with 5 relapses and 70% with 6 events, respectively. Presence of CA impacted adversely the EFS: 61% of patients without CA vs. 39% of those with CA (Logrank p = 0.06). However, a history of prior relapse or high LDH was not associated with inferior EFS: 42% with prior relapse vs. 76% without prior relapse (p = 0.27); 45% with high LDH vs. 51% with normal LDH (p = 0.86). Although the current findings are limited by the small number of patients and the short duration of follow-up, the data suggests that additional bortezomib to the standard high-dose melphalan and implementation of long-term maintenance post-transplant with bortezomib and lenalidomide may overcome the adverse factors in high-risk MM patients for relapse. Further study is necessary to confirm the findings.

Disclosures:
Myint: Seattle Genetics, Inc.: Research Funding.