Importance of achieving stringent complete response after autologous stem-cell transplantation in multiple myeloma

Abstract

Purpose: To study the impact of achieving stringent complete response (sCR), an increasingly attainable goal, after autologous stem-cell transplantation (ASCT) in patients with multiple myeloma (MM).

Patients and methods: Maximal response rates were determined in 445 consecutive patients who underwent ASCT within 12 months of diagnosis of MM. The patients achieving varying degrees of complete response (CR) are the focus of our study.

Results: One hundred and nine patients (25%) achieved sCR after ASCT. The median overall survival (OS) rate from the time of transplantation for patients attaining sCR was not reached (NR), in contrast to those patients achieving conventional complete response (CR; n = 37; OS, 81 months) or near CR (nCR; n = 91; OS, 60 months; P < .001). Five-year OS rates were 80%, 53%, and 47% for sCR, CR, and nCR, respectively. The median time to progression (TTP) from ASCT of patients achieving sCR was significantly longer (50 months) than TTP of patients achieving CR or nCR (20 months and 19 months, respectively). On multivariable analysis, post-ASCT response of sCR was an independent prognostic factor for survival (hazard ratio, 0.44; 95% CI, 0.25 to 0.80; versus CR; P = .008), in addition to proliferation rate, pre-ASCT cytogenetics, and performance status. OS rates of patients attaining sCR continued to remain superior at 2-year landmark (median, NR v 70 months for conventional CR group; P = .007).

Conclusion: Improved long-term outcome is seen after ASCT with achievement of sCR when compared with lesser degrees of responses. Myeloma trials reporting the response rates should identify patients achieving sCR and CR separately, owing to markedly disparate outcomes of the two categories.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.

Best responses for 445 patients after autologous stem-cell transplantation. The response categories achieved by the patients were stringent complete response (sCR; n = 109), complete response (CR; n = 37), near complete response (nCR; n = 91), very good partial response (VGPR [excluding nCR]; n = 60), partial response (PR; n = 109), stable disease (SD; n = 21), and progressive disease (PD; n = 18). The sum of percentages is slightly greater than 100 because of rounding.

Fig 2.

(A) The median time to progression (TTP) of patients achieving at least a complete response (CR; n = 146; 33%) is 39 months (95% CI, 33 to 48) compared with 20 (95% CI, 17 to 22), 17 (95% CI, 14 to 21), and 18 (95% CI, 9 to 25) months, respectively, for those achieving very good partial response (VGPR; including near complete response [nCR] as per International Myeloma Working Group definition; n = 151; 34%), partial response (PR; n = 109; 24%), and stable disease (SD; n = 21; 5%). Patients with progressive disease (PD; n = 18; 4%) had a short median TTP of 3 months (95% CI, 2.7 to 4). (B) Median TTP of patients achieving stringent complete response (sCR; n = 109) is 50 months (4.2 years; 95% CI, 36 to 63 months) compared with 20 months (1.7 years; 95% CI,15 to 36) and 19 months (1.6 years; 95% CI, 16 to 22 months) for groups attaining CR (n = 37) and nCR (n = 91), respectively (P < .001).

Fig 3.

(A) Overall survival (OS) curves against response categories. The median OS of the patients achieving at least a complete response (CR; n = 146) was 109 months (9 years; 95% CI, 94 to not reached [NR]) compared with 64 months (5.3 years; 95% CI, 53 to 78 months), 59 months (4.9 years; 95% CI, 50 to 86 months), 56 months (4.6 years; 95% CI, 40 months to NR), respectively, for those achieving very good partial response (VGPR; n = 151), partial response (PR; n = 109), and stable disease (SD; n = 21). Patients with progressive disease (PD) survived for a median of 9 months (0.8 years; 95% CI, 5 to 88 months; P < .001). (B) OS of the patients achieving varying degrees of CR. Those with stringent complete response (sCR; n = 109) had a marked improvement in OS (median OS, NR; 95% CI, NR to NR) compared with the patients achieving CR (n = 37; median OS, 81 months; 95% CI, 37 to 109 months) or near complete response (nCR; n = 91; median OS, 60 months; 95% CI, 47 to 78). The 5-year OS is 80%, 53%, and 47%, for patients achieving sCR, CR, and nCR, respectively (P < .001).

Fig 4.

(A) Landmark analysis at 2 years studying survival outcomes of patients undergoing early autologous stem-cell transplantation (ASCT) and achieving stringent complete response (sCR; n = 105) versus complete response (CR; n = 32). Median overall survival (OS) was not reached for patients with sCR, but patients achieving CR had median OS of 70 months (5.8 years; P = .007). (B) Among patients receiving early transplantations who achieved sCR (n = 109), OS of patients with sustained sCR (n = 75) at 6 months from ASCT was not reached (7-year OS, 86%) versus median OS of 66 months or 5.5 years for those who had nonsustained-sCR (n = 34) after ASCT (7-year OS, 37%; P < .001).