Induction with an Oral Chemotherapy-Cyclophosphamide in Combination with Idarubicin and Dexamethasone (CID) Followed by Early Autologous Stem Cell Transplantation for Multiple Myeloma Patients.
Authors: Pati Nalini K. , Kwan Yiu-Lam , Manoharan Arumugam , Teh Michael 
Published: October 2019

INTRODUCTION: In many centers an initial period of induction treatment followed by peripheral blood stem cell (PBSC) harvest and autologous stem cell transplantation (ASCT) has become standard of care for multiple myeloma (MM) in patients =< 65 years of age. Commonly induction regimens contain intravenous cytotoxic agents and oral corticosteroids. There are interests in oral regimens, including thalidomide-containing combinations (1). Recently Spencer et al from Australia reported a small multicenter study in which the induction treatment prior to ASCT comprised an outpatient-based oral chemotherapeutic regimen CID-- cyclophosphamide, idarubicin, dexamethasone, in previously untreated MM patients (2).

AIM: To evaluate the efficacy of oral CID in MM in our own institution.

METHODS: thirteen patients with MM (relapsed n=2, previously untreated n=11) were treated with CID. Courses were repeated every four weeks, with the aim of harvesting PBSC after 3 to 6 courses, depending on response. Efficacy of treatment was assessed on the following parameters: paraprotein level, b2 microglubulin and bone marrow plasma cell content. Wilcoxon Signed Ranks Test was used to analyze treatment outcomes and Kaplan-Meier curves were used for analysis of overall survival and event free survival.

RESULTS: All 13 patients (median age 61 yrs, range-41–72 yrs; male-7, female-6) were evaluable for response, with a median follow up of 40 (12–84) weeks. In total, eleven patients (10 previously untreated, and one relapsed) were planned to have an elective ASCT. All had successful stem cell mobilization after 3–6 cycles of chemotherapy, and subsequently received an ASCT. One patient died 42 days post transplantation due to infection and ARDS. The median time between completion of CID and ABMT was 6 weeks (range 4–16).

One previously untreated patient and one relapsed patient, both aged >65, received CID only without an ASCT. Comparison of pre and post chemotherapy levels of paraprotein, b2 microglubulin and bone marrow plasma cell content showed statistically significant results with p values of 0.002, 0.001 and 0.002 respectively. According to International standard criteria, 3/13 achieved complete response (CR), 7/13 had very good partial response (VGPR) or partial response (PR), 1/13 stable disease (SD) and 2/13 had relapse or progressive disease (PD), resulting in an overall response rate (>/=SD) of 84%. The median time to maximum response was 4 months. The Kaplan-Meier estimates of event-free survival and overall survival at 1 year were 64% and 84%, respectively.

There were no major toxicities except weight gain (National Cancer Institute Common Toxicity Criteria Grade III) was seen in 23% of the patients, possibly due to the dexamethasone component in CID.

CONCLUSIONS: Our results confirm the efficacy and safety of this outpatient based all oral induction regimen for patients with MM. The favorable side effect profile, the convenience of drug delivery with oral dosing, and the ease of PBSC mobilisation are the main advantages.