Complete Remission Represents the Major Surrogate Marker of Long Survival in Multiple Myeloma.

Abstract

Abstract The impact of complete remission of myeloma on long term outcome remains controversial. Between January 1987 and May 2006, we evaluated frequencies of partial and complete remission, and survival from onset of therapy, for 721 consecutive, newly diagnosed patients who received a high-dose, dexamethasone-based combination as primary treatment. Only patients <65 for whom intensive therapy was a uniform option were included; 45 patients with nonsecretory myeloma protein or with <50 mg/day of only Bence Jones protein were excluded in order to provide a valid myeloma protein marker in all patients. Criteria for partial response (PR) required reduction of serum myeloma protein level by >50% and of Bence Jones protein by >90%; complete remission (CR) was defined by negative findings on immunofixation. Among 721 previously untreated patients, the initial response rate was 57%, including 8% with CR. Within 12 months, 397 patients received intensive therapy with a high-dose, melphalan-based regimen supported by autologous stem cells. In comparison with non-transplanted patients, intensified patients were younger (median 52 vs 56 yrs), more anemic (median 10.3 vs 11.3 gms/dl), and had more patients with stage 3 disease by ISS criteria (37% vs 25%) (p<.01). Intensive therapy converted PR to CR in 34%, resistant disease (NR) to PR in 51%, and NR to CR in 14% of patients. For 209 patients with persistent resistant disease, the median survival was 2 yrs. Among 384 patients who achieved PR as maximum benefit, median survival times were significantly longer for 164 patients who received only primary treatment (4.3 yrs) and for 67 patients converted from NR to PR by intensive treatment (4.3 yrs) (p<.01); survival was even longer for 153 patients with persistent PR after intensive therapy (5.9 yrs) (p<.01), an outcome attributed to the high frequency of further moderate reduction of responsive myeloma after high-dose therapy even without CR. For 124 patients who achieved CR after only primary therapy or after intensive therapy of PR or NR, the median time to CR was 3 months (range 1–12 months) and median survival times of 10–14 yrs were similar; the median survival of 9 yrs for 32 patients intensified in CR was also similar, suggesting that high-dose therapy provided no further benefit after CR had been achieved with initial therapy. A randomized trial may be useful to clarify this question. Among the patients who died in CR, the cause of death was unrelated to myeloma in 20%, justifying future analyses of disease-related survival for such patients. Prolongation of survival was evident primarily when intensive therapy induced a major reduction of the myeloma and especially to CR. The sensitivity of myeloma to intensive therapy declined progressively for patients treated in NR, PR, or CR.