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High dose chemotherapy (HDC) followed by autologous stem cell transplantation (ASCT) is the standard treatment approach for younger patients with multiple myeloma (MM). Since the introduction of proteasome inhibitors and immunomodulatory drugs in MM treatment more patients achieve deep and durable responses and better disease control before ASCT.

To evaluate the association between the depth of response before ASCT and survival outcomes in a cohort of patients with MM.

Retrospective analysis of patients with MM treated with HDT and ASCT between 2007 and 2016 in a single institution. All patients received peripheral blood stem cell support after conditioning with high dose melphalan (200 mg/m² and 140mg/m² for patients with renal insufficiency). Response was assessed 100 days after ASCT according to the International Myeloma Working Group response criteria. The Kaplan-Meier method was used to estimate progression free survival (PFS) and overall survival (OS) and comparison between risk groups was performed by using the log-rank test. The prognostic factors of survival were analyzed by Cox regression univariate and multivariate analysis.

We included 195 MM patients, mainly males (57.9%) with a median age at ASCT of 61 years (28-71). The most prevalent subtype was IgG k (44.1%). The median number of previous therapeutic lines was 1 (1-4) and the majority of patients (61%) received bortezomib as part of first-line regimen. Patients undergone ASCT within a median of 10 months after diagnosis. With a median follow-up time from ASCT of 28.55 months (2.8-121.4), OS at 2 and 5 years was 83.8% and 68.9% and PFS was 74.8% and 37.3%, respectively. Before ASCT, 101 patients (51.8%) achieved very good partial response (VGPR) or better (≥VGPR) and 94 patients (48.2%) a partial response (PR). The patients in ≥VGPR presented significantly longer OS (median OS not reached vs 96.9 months, p=0.023) and PFS (58.5 vs 41.2 months, p = 0.003) compared with those in PR. At 100 days after ASCT, 107 patients (54.9%) presented ≥VGPR, 79 (40.5%) PR and 7 (3.6%) progressive disease. Two patients were not assessed due to loss of follow-up. The group of ≥VGPR showed superior OS (median OS not reached vs 72.4 months, p=0.023) and PFS (58.5 vs 34.79 months, p=0.007) compared to the PR group. We did not found statistically significant differences in survival of patients who achieved ≥VGPR before or after ASCT. Univariate analysis indicates that depth of response before and after ASCT (≥VGPR vs PR) are significant predictors of OS (HR 0.49; 95% CI 0.31-0.80, p=0.004 and HR 0.49; 95% CI 0.30-0.81, p=0.005) and PFS (HR 0.50; 95% CI 0.27-0.92, p=0.026 and HR 0.49; 95% CI 0.27-0.90, p=0.021). Multivariate Cox regression model showed that these factors retain their prognostic value after adjustment for age, International Staging System stage and number of previous lines of treatment.

These findings provide evidence for quality of response as a predictor of OS and PFS after ASCT in patients with MM. Outcome after ASCT seems to be better for MM patients who achieve deep responses (at least VGPR) before or after transplant. Our results support the use of more effective induction regimens in order to improve initial response as this may correlate with higher response rates and survival post-ACST.