Induction Therapy with High-Dose Dex Alone in Newly Diagnosed Myeloma Patients Produces a 57% Partial Response and Is Predictive of Progression Free Survival.
Authors: Irvine David A. , Barnett Michael J. , Brinkman Ryan , Forrest Donna L. , Hogge Donna E. , Lavoie Julye , Lei Linda , Nantel Stephen H. , Nevill Thomas J. , Nitta Janet , Shepherd John , Song Kevin , Toze Cynthia , Sutherland Heather 
Published: October 2019

Abstract
Induction chemotherapy followed by autologous stem cell transplant (ASCT) has become standard treatment for symptomatic myeloma patients. Our strategy has been to use the Dex component of the VAD protocol alone for 2–4 cycles as induction. Between January 1998 and May 2005, 406 pts were referred to us for treatment of multiple myeloma. We retrospectively reviewed all pts in order to determine the rate and depth of response to Dex, to determine if response predicted overall survival (OS) or progression free survival (PFS) and assess factors predictive of response. Of 406 pts, 124 were excluded due to prior therapy, no treatment or lack of response data. Analysis was performed on 282 pts all of whom received single agent Dex as primary therapy for newly diagnosed myeloma given at 40mg on days 1–4, 9–12, 17–20 every 28 days for at least two cycles. 40% were female and 60% male and median age was 56. Myeloma subtypes were: IgA 21%; IgG 56%; light chain (LC) 17%, nonsecretory 2% and others 1.4%. Cytogenetic information was available in 51% of pts with 53 confirmed as having a deletion on chromosome 13 (del13q). Response to Dex induction therapy was as follows; nCR [no M protein, IF not performed] 4%, PR1 [>90% reduction in M protein/involved Ig subtype] 10%, PR2 [>50% reduction] 43%, MR [>25% reduction] 20%, no response (NR) [within 25% of base level] 14% and progressive disease (PD) [increase by >25%] 7%. 241 proceeded to transplantation; 212 underwent auto SCT with a melphalan based conditioning regimen after stem cell mobilization with cyclophosphamide and GCSF, 29 had an allo SCT. We evaluated the effect of del13q, International Staging System (ISS), b2Microglobin (b2M), sex, age, Salmon-Durie stage, hypercalcemia, Ig subtype, creatinine and hemoglobin at diagnosis (Hgbdx) on response to Dex, OS and PFS from treatment initiation. Univariate analysis showed that OS was significantly affected by Hgbdx >/≤10g/dl, ISS score and b2M >/≤3.5 while PFS was influenced by b2M <3.5, ISS score, and best response to Dex (p<0.001) with those reaching PR1 achieving a median PFS of 1181d and PR2, MR, NR and PD having median PFS of 1031d, 729d, 825d, 61d respectively. In the group proceeding to HDT similar relationships were noted with PFS post transplant (PFSB) significantly affected by ISS score (median survival for ISS I, II and III 1201d, 848d, 621d respectively) [p=0.047], b2M <3.5 (median survival 1225d vs. 621d) [p=0.013] and best response to Dex. Multivariate analysis confirmed depth of response to Dex as a prognostic factor in PFSB. Analysis of factors which might predict which patients are most likely to respond well to Dex using the chi square contingency table demonstrated that ISS score, B2M>2.5 and Ig subtype significantly influenced response (p<0.05). In conclusion; 43% of pts do not achieve at least a PR with single agent Dex induction, and 7% progress. Despite subsequent treatment with high dose Melphalan and autotransplant in most patients in this study, the depth of response to Dex remains predictive of PFS. While it is unknown whether this reflects disease biology, it seems rational to evaluate new lines of anti-myeloma therapy in an attempt to improve depth and frequency of response and evaluate whether this influences long-term PFS.