The Impact of Different Pre-Transplant Regimens Including Novel Agents On Peripheral Blood Mobilization, Harvest, Response and Survival in Patients Undergoing ASCT for Multiple Myeloma. A Single-Center Experience in 210 Patients.

Abstract 2279

Poster Board II-256

High dose therapy (HDT) with autologous stem cell transplantation (ASCT) has become the standard of care for eligible patients with multiple myeloma (MM) younger than 65 years. Induction therapy with combination regimens such as VAD or single agent dexamethasone has little impact on SC mobilization and offers a PFS of 12-18 months post-ASCT. Recently, novel agents (IMiDs and bortezomib) are used in the induction regimens prior to ASCT. The aim of this study was to assess the impact of conventional and novel agent-based induction regimens on SC harvest, response and survival among patients with MM treated in the Department of Clinical Therapeutics of the University of Athens, Greece. From January 1996 to June 2009, 210 consecutive patients who underwent ASCT were classified according to the induction regimens to: those who had received conventional chemotherapy (CC) only (MP, CD or VAD) (group A); those who were treated with CC followed by novel agent-based regimens (dexamethasone plus an IMiD and/or bortezomib; group B); and patients who were treated with novel agent-based regimens only prior to SC collection (group C). Stem cells were mobilized with G-CSF alone or with cyclophosphamide and G-CSF. Group A included 102 (49%) patients, group B 72 (34%) and group C 33 (16%) patients. Induction with novel agents only (group C) yielded a significantly greater SC collection compared to induction with CC only (group A) or CC followed by novel agent-based therapies (group B) (p=0.006 and p=0.038, respectively). The mean number of collected CD34+ cells/kg was 10×10⁶ (range 2-43.2×10⁶), 10.4×10⁶ (range 2-49×10⁶) and 15.1×10⁶ (range 2-65×10⁶) for groups A, B and C, respectively. The probability to collect a number of at least 5×10⁶ CD34+ cells/kg was significantly higher in patients who received novel agents only when compared to those of groups A and B (78.8% vs. 57.5%, p=0.021). Among patients of group A, those who received induction with VAD had a significantly greater SC collection when compared to MP or CD (mean CD34+ cells/kg collected: 12.2×10⁶vs. 7.56×10⁶ /kg; p=0.031). Moreover, SC yield did not differ between patients who received VAD only or novel agent-based regimens only, as induction therapy (p=0.155). Engraftment data were comparable between the three groups. Age >55 years (p=0.039) and prior radiation therapy (p<0.0001) negatively influenced SC collection. The administration of novel agent-based regimens alone was associated with superior response rate prior to ASCT compared to CC alone as induction therapy (objective response (OR) 87.5% vs. 61.7%, p=0.007; at least vgPR 27.2% vs. 18.9%, p=0.032, for groups C and A, respectively). However, post-ASCT, patients of groups A and C achieved similar response rates (OR: 94.6% vs. 92.9%, p=0.736 and at least vgPR: 53.6% vs. 46.7%, p=0.526). The median OS, from the date of ASCT, in all patients was 74 months. Factors associated with longer OS included the achievement of CR or sCR post-ASCT (p=0.027), ISS-1 and -2 vs. ISS-3 (p=0.007), low beta2-microglobulin (<3.5 mg/mL) prior to ASCT (p=0.023), low marrow infiltration by plasma cells (<5%) prior to ASCT (p=0.016) and normal MRI pattern at diagnosis (vs. focal and diffuse, p=0.027). The use of novel agent-based regimens in induction therapy was associated with a probability of 4-year OS of 88% compared to 54% in patients of group A. There was a trend in favor of novel agent-based regimens as induction therapy in terms of OS (median 89 vs. 62 months, for patients of groups B+C and A, respectively; p=0.144). Furthermore, patients of group C had superior EFS post-ASCT compared to patients of group A (median 84 vs. 27 months; p=0.046). Other variables like mobilization regimen before HDT (cyclo 4g/m²+G-CSF vs. cyclo 2.5 g/m²+G-CSF vs. G-CSF only), high dose therapy dosage (melphalan 200 mg/m²vs. 180 mg/m²vs. 140mg/m² or less), and the interval from diagnosis to ASCT (more or less than one year) did not correlate with OS or PFS. In conclusion, our study demonstrates that patients who received induction therapy with novel agents only prior to ASCT had a higher number of CD34+ cells collected when compared to induction with CC followed by novel agent-based regimens or CC alone. Furthermore, these patients achieved a higher response rate and a better quality of response before HDT, compared to patients who received CC only, but this did not correspond to a higher response rate post-ASCT. Further follow-up is needed to fully assess the impact of novel agent induction on patient's OS.