The Type of Upfront Induction Therapy for Newly Diagnosed Multiple Myeloma Patients Has No Significant Impact on Clinical Outcomes after Autologous Hematopoietic Stem Cell Transplantation.
Authors: Chung Stephen S. , Spitzer Thomas R. , Ting David T. , Dube Christine , Yee Andrew J. , Ballen Karen , McAfee Steven L. , Attar Eyal , Dey Bimalangshu R. 
Published: October 2019

Abstract
Randomized trials that incorporated high-dose chemotherapy (HDC) plus autologous hematopoietic stem cell transplantation (AHSCT) into the early treatment of patients with newly diagnosed multiple myeloma have demonstrated superior overall (OS) and progression-free survival (PFS) in patients 65 years of age or younger who received AHSCT as compared with patients who received conventional chemotherapy. Based on these results, AHSCT is recommended for patients with myeloma as part of their initial treatment. All patients in these trials received four to six months of conventional chemotherapy prior to HDC and AHSCT. In practice, however, patients are undergoing AHSCT after being treated with various first-line regimens, including chemotherapeutics, high-dose dexamethasone (HDex), immunomodulatory drugs such as thalidomide and recently, proteasome inhibitors. In this retrospective study, we examined the impact of first-line therapy on the outcomes following AHSCT. Our objective was to compare two induction treatment groups, chemotherapy versus non-chemotherapy, prior to AHSCT with respect to disease-specific survival after AHSCT. Between 1997 and 2006, 45 previously untreated evaluable patients with multiple myeloma received either chemotherapy (n=25; VAD, n=24; MP, n=1) or non-chemotherapy induction regimens (n=20; HDex, n=9; thalidomide plus HDex, n=8; bortezomib, thalidomide, and HDex, n=3), then received high dose melphalan plus granulocyte colony stimulating factor-mobilized AHSCT. Twenty-three patients in the chemotherapy group (92%) and fifteen patients in the non-chemotherapy group (75%) had stage III disease; median times from diagnosis to AHSCT were 6 months (range 4–18) and 8 months (range 5–26), respectively, in chemotherapy and non-chemotherapy groups. At day +100 after transplant, the rates of complete and near-complete response were 47% in the chemotherapy group (17 of 25 patients had adequate staging data available) and 69% in the non-chemotherapy group (16 of 20 patients had adequate staging data available) (p=0.211). The median PFS was 26 months (95% CI, 16-inf) in the chemotherapy group and 29 months (95% CI, 16-inf) in the non-chemotherapy group. The median OS from transplant was 51 months (95% CI 29–77) in the chemotherapy group and 66 months (95% CI 40–inf) in the non-chemotherapy group. The difference in PFS and OS between the two groups was not statistically significant (p=0.805 and p=0.643, respectively). PFS at two years (of whom 25 of 25 patients in chemo group but only 12 of 20 patients in non-chemo group had reached) was 56% in the chemo group and 42% in the non-chemo group. OS at two years follow-up was 76% in the chemo group and 75% in the non-chemo group. The difference in PFS and OS between the two groups was again not statistically significant (p=0.424, p=0.960, respectively). In conclusion, patients with newly diagnosed myeloma, when treated with dose-intensive chemotherapy and AHSCT, may achieve similar long-term PFS and OS regardless of the type of upfront induction therapy used.