Long-Term Survival for Myeloma after Autologous Stem Cell Transplantation

Introduction: Multiple myeloma (MM) remains incurable with only a small proportion of patients surviving over 10 years (long-term survivors) from diagnosis. It has been more than 3 decades since the first autologous stem cell transplantation (ASCT) was performed for MM at our institution. In this study, we sought to determine baseline patient and disease characteristics that are associated with long-term survival after the ASCT.

Methods: We included all consecutive patients who received their first ASCT between January 1988 and December 2015. The primary objective was to identify the variables associated with long-term overall survival (>10 years). The control group were patients who survived less than 10 years from their diagnosis data (short-term survivors). Logistic regression models were used to evaluate the association between predictive factors and overall survival of > 10 years.

Results: Among 2176 patients who underwent their first ASCT during the study period, 1409 patients met the eligibility criteria. Overall, 392 (28%) patients were long-term survivors (>10 years) and 1017 (72%) were short-term survivors (<10 years). Table 1 shows baseline patient and disease characteristics. Only 24% and 42% of patients in the long-term and short-term survivor groups, respectively, received proteasome inhibitor-based induction therapies. Maintenance therapy was received by 49% and 45% in the short- and long-term survivor groups, respectively (p=0.19). The long-term survivor group was characterized by having higher percentage of patients younger than age 65 (86%) years, and having higher proportions of ISS Stage I (47%), standard-risk cytogenetics (96%), normal LDH (88%) and with serum creatinine <2 mg/d (87%). With a median follow-up of 13 years (range, 10-30 years), the 15-year PFS and OS survival rates in the long-term survivors were 19% (95% CI: 14% - 23%) and 62% (95%: CI 56% - 68%) (Figure 1A). The cumulative incidence rates of relapse at 1, 3, and 5 years in the short-term survival group were 9%, 63%, and 82%, respectively, compared to 2%, 20%, and 40%, respectively, in the long-term survivor group (p<0.001) (Figure 1B). All variables listed in Table 1 were assessed in univariate analysis. Seventy-six percent of patients were relapse-free at 24 months in the long-term survival group, compared to only 32% in the short-term survival group. On multivariable analysis, age, cytogenetic-risk status, race-ethnicity, and duration of remission after ASCT were significant predictors for surviving > 10 years (Table 2). ISS Stage III (vs. Stage I: OR 0.45, 95% CI 0.19-1.09; p=0.08) showed a trend towards surviving ≤ 10 years.

Conclusions: ASCT is associated with durable responses and prolonged survival in a subgroup of MM patients irrespective of type of induction therapy and/or use of maintenance therapy. Duration of remission after transplant is the strongest predictor for long-term survival. Age <65 years, being African-American, and standard-risk cytogenetics were also associated with surviving more than 10 years.