Lack of Significance of ISS Staging and Depth of Response in Predicting Overall Survival for Multiple Myeloma Patients

Introduction: Despite the advances for treating multiple myeloma (MM) patients (pts), it remains an incurable B-cell malignancy. Thus, the objective for treating these pts is to prolong overall survival (OS) and preserve quality of life. New classes of drugs in the past decade have improved OS for MM pts; however, most of the studies conducted to predict outcome and predict factors that determine OS have relied on older data sets derived from large institutions including pts not receiving treatment there and lacking accurate follow up of pts as well as information from centers in which therapeutic choices are limited. These studies have suggested that depth of response, specifically complete response (CR), and lower International Staging System (ISS) staging at diagnosis predict improved OS. We have now analyzed data on all MM pts who have received treatment in a single clinic specializing in MM.

Methods: Data was obtained from all MM pts who received treatment in a single clinic specializing in MM that was established 10 years ago. Kaplan-Meier analysis was used to generate all survival curves and the log-rank test was used to measure difference between curves, with P<0.05 representing statistical significance.

Results: Two hundred sixty-three MM patients (161 male, 102 female) with a median follow-up of 52 months were analyzed in this study. The median age at diagnosis was 63 years (range, 31 to 88). Thirty-seven pts (14%) had smoldering MM (SMM) while the remainder (n=225 [86%]) were diagnosed with active MM. For pts with active disease, ISS staging at diagnosis (n=156) included 68 (44%), 46 (29%) and 42 (27%) pts with ISS Stages I, II and III. The median OS of all patients was 118 months with a 5-year survival of 77%. The 5-year OS of SMM pts was 88% compared to 76% for those with active disease. There were no significant differences in OS between pts with different ISS stages at the time of diagnosis. Specifically, the median 5-year survival of pts with ISS Stage I, II and III disease at diagnosis were 79, 91 and 84 months, respectively.

We also analyzed OS of MM pts according to the depth of response from treatment. There were no significant differences in OS between pts who attained a CR during their first treatment regimen compared to those who achieved their first CR during subsequent regimens or those who never attained a CR. During their first treatment, pts with stable disease (SD; n=28) showed no difference in OS compared to those achieving > minimal response (MR; n=135), > partial response (PR; n=107), PR (n=72), or CR (n=35). The OS of pts who had achieved a CR with at least one regimen (n=83 [38% of pts]) was not different than among pts never achieving CR (n=135 [62% of pts]; P=0.1173). In order to further determine whether depth of response predicts OS during the patient’s course of disease, OS was determined based on the best response ever achieved to any anti-myeloma regimen. There was no significant difference in OS between patients who achieved a CR (n=84) with any treatment regimen compared to those who attained an MR or PR (n=108), PR (n=73), MR (n=35) or those who had achieved only an SD (n=11). However, OS among pts who achieved CR, > PR, ≥ MR, or > SD (SD+MR+PR+CR) was better than among those who had only demonstrated PD during their course of disease (P<0.0001).

In order to determine whether the initial treatment regimen predicted OS, we also analyzed survival of pts who received bortezomib-based therapy compared to those who received an IMiD or both drugs together as their initial treatment, and showed there was no significant differences in OS between these three upfront treatment approaches.

Conclusion: Results from an analysis of a large cohort of MM pts from a single clinic specializing in MM show that the median survival has greatly improved to nearly 10 years due to the availability of many new treatment options. Although previous studies have suggested that ISS staging at diagnosis and depth of response to anti-MM regimens predict OS for MM pts, results from our study involving analysis of a large cohort of MM pts from a single clinic specializing in MM show that these prognostic factors do not predict OS for pts with this B-cell malignancy. Differences in our results compared to other previous studies may reflect the many treatment options available in the clinical setting used to obtain our results.