CR represents an early index of potential long survival in multiple myeloma

Abstract

To assess the impact of CR on survival in multiple myeloma. Retrospective evaluation of response and survival among 758 consecutive patients with multiple myeloma treated at a single center, of whom 395 patients received intensive therapy supported by autologous stem cells within the first year. Survival times were calculated after 1 and 2 years from the start of chemotherapy. On the basis of the response status after a 2-year landmark, the subsequent median survival was 9.7 years for patients with CR, 4.4 years for those with PR and 2.7 years for patients with NR (P<0.001). Longer survival was attributed in part to intensive therapy that converted the myeloma of 67% of patients with NR to PR or CR, and induced CR in 26% of patients with PR. Intensive therapy did not prolong survival for patients with CR after primary therapy. For patients with multiple myeloma, Cox regression analyses showed that CR was the dominant prognostic factor for long survival, followed by stage I disease, PR and intensive treatment as independent factors. A cure fraction of 2% was identified for nine patients who have remained in CR >10 years.

Figure 1

(Left panel) Survival from primary treatment for all patients who received or did not receive HDT within the first year. (Right panel) Survival from primary treatment for all patients with myeloma in CR, PR or NR as best outcome.

Figure 2

(Left panel) OS by landmark analysis for 291 patients who received chemotherapy alone based on response status at 12 months. The percentages of CR, PR and NR defined at 12 months were 9, 58 and 33%, respectively. Among 25 patients with CR, initial therapy had been dexamethasone (D) in 19, thalidomide-dexamethasone (TD) in 3, and bortezomib-thalidomide-dexamethasone (BTD) in 3; among 170 patients with PR, initial therapy had been D in 154, TD in 11 and BTD in 5. (Right panel) OS of 375 patients who received chemotherapy followed by HDT within 1 year based on response status at 12 months. The percentages of CR, PR and NR defined at 12 months were 27, 64 and 9%, respectively. Among 102 patients in CR, initial therapy had been D in 50, TD in 35 and BTD in 17; among 238 patients with PR, initial therapy had been D in 152, TD in 65 and BTD in 21.

Figure 3

(Top panel) OS by landmark analysis of 2 years for patients who achieved CR after chemotherapy alone or after added HDT. Among 23 patients with CR without HDT, initial therapy had been dexamethasone (D) in 18, thalidomide-dexamethasone (TD) in 3 and bortezomib-thalidomide-dexamethasone (BTD) in 2; among 29 patients with intensive therapy of CR, initial therapy had been D in 14, TD in 10 and BTD in 5. (Middle panel) OS by landmark analysis of 2 years for 350 patients with PR who received HDT. Among 74 patients with CR, initial therapy had been D in 46, TD in 21 and BTD in 7; among 140 patients with PR, initial therapy had been D in 81, TD in 48 and BTD in 11; among 136 patients who achieved PR after chemotherapy alone, initial treatment had been D in 125, TD in 10 and BTD in 1. (Lower panel) OS by landmark analysis of 2 years for 150 patients with NR who received HDT. Among 12 patients with CR, initial therapy had been D in 8, and TD in 4; among 48 patients with PR, initial therapy had been D in 32, TD in 13 and BTD in 3; among 24 patients who remained NR despite HDT, initial therapy had been D in 18 and TD in 6; for 66 patients who remained NR after chemotherapy alone, initial treatment had been D in 64 and TD in 2.

Figure 4

OS of patients by a landmark analysis of 1 year by ISS stage and eventual response status at 1 year. The percentages of patients with ISS I + CR, ISS II/III + CR, ISS I + PR/NR or ISS II/III + PR/NR were 10, 10, 34 and 46%, respectively.