Curability of Multiple Myeloma.

Among patients with multiple myeloma, superior drug combinations and the wider application of early intensive therapy (HDT) have induced more frequent partial (PR) and complete remissions (CR), with consequent longer survival. A recent multivariate analysis identified complete or partial remission status, ISS Stage I disease and HDT as independent variables for long survival and we therefore sought to examine these relationships further.

We updated our experience with 829 patients, aged <65, who had been treated between 1987- 2008 with various dexamethasone-based combinations (D).

Induction therapy was followed by early HDT within first year for 53% of patients, so that the myeloma of 21% of patients was in CR within 18 months. Frequencies of CR increased serially from 16% with primary D (alone, with interferon, melphalan or VAD), to 29% with added thalidomide (T) and to 42% with added T and bortezomib (or lenalidomide) (p<.01). Survival and complete remission times were evaluated after landmark of 18 months, thus excluding 128 patients who had died (NR 59%, PR 38%, CR 3%). Only when CR duration exceeded 2 years (106 patients) was survival (median 12.9 years) longer than those of patients with CR < 2 years (median 3.8 years), or with PR (median 4.1 years) (p<.01), supporting findings by Barlogie et al on the importance of sustained CR for long survival. Survival of 24 patients with CR achieved after primary therapy alone (median 12.9 years) was similar to that of 35 patients with added HDT for consolidation of CR (median 15.1 years), but slightly longer than that of 102 patients with conversion to CR after HDT for PR or NR (median 8.2 years, p=.12 ). In order to define favorable features associated with very long CR, we identified 11 patients with duration of CR >10 years who had been treated with primary D between 1987 -1997. Using the log rank test, the median age was less (46 vs 54, p=.04), while the chi-square test showed ISS Stage I more common (64 vs 40%, p=.11), and early HDT more frequent (73 vs 26%, p.<01), than the features of 366 other patients treated during this period without such long CR. Among the 11 patients, the myeloma of 7 patients was in CR after primary therapy of whom 4 patients also received HDT; disease in the remaining 4 patients reached CR status only after HDT for PR (3) or NR (1). The myeloma has relapsed in 2 patients (CR duration 11.3 and 11.9 years), while CR has been sustained in 9 patients without maintenance for >10-19 years (median 16.2 years). Thus, prolonged CR was more frequent with younger age, stage I disease, and early HDT.

Assuming that prolonged CR for more than 10 years translates into potential cure, we calculated a “cure fraction” of 2% for patients treated between 1987 -1997. Such favorable outcome with potential cure should be more likely with current programs associated with more frequent HDT and CR.

No relevant conflicts of interest to declare.