Abstract

Introduction: Quality of response to treatment in relapse/refractory MM, especially complete response (CR) or near complete response (nCR), has been reported to correlate with better PFS and OS in the past (

Hussein MA, et al.
Mayo Clin Proc
2006
;
81
:
889
–95
). In this report, we provide an update on long-term survival from two multicentre phase II trials using thalidomide +/- IFNα2B (MM-thal) and combination celecoxib-thalidomide (Cel-thal) in relapsed or refractory MM, and identify predictors of progression-free survival (PFS) beyond 24 months (m).

Method: In 1998 and 2001, two prospective multicentre phase-II trials in relapsed or refractory MM were performed to assess the efficacy of thalidomide +/- IFNα2B (MM-thal), and combination celecoxib-thalidomide (Cel-thal), respectively. Both studies were previously reported (

Blood
2003
;
102
:
69
;
Clin Can Res
2005
;
11
:
5504
). The analysis of progression free survival (PFS) has been updated using the Kaplan-Meier method. Baseline characteristics were compared between patients having PFS ≥ 24m and < 24m using fisher’s exact test or the Cochran-Armitage test, to identify predictors of long-term disease control.

Result: Median follow up for MM-thal (n=75) and Cel-thal (n=66) trials were 73m and 47m respectively. Median PFS in the MM-thal trial was 5.5m, with estimated PFS of 9% at 3 years (95%, CI:5-18%), and 5% at 5 years (95%, CI:2-13%). In the Cel-thal trial, median PFS was 6.8m, with estimated PFS of 21% at 3 years (95% CI: 13-33%) and 16% at 5 years (95% CI:9-27%). Overall, 27 out of 141 patients (10 from MM-thal, 17 from Cel-thal) had PFS beyond 24m. The majority of these long term responders (70%) achieved only a PR as the best response to thalidomide-based treatment;15% achieved complete response (CR), and 15% had stable disease (SD). The most significant predictors for prolonged PFS of ≥24m was β2M ≥3mg/l (p<0.0005), stage ≥2 disease (p=0.001), and non-refractory disease to previous therapy (p=0.03). Bone marrow plasma cell infiltrate following thalidomide did not predict for outcome.

Conclusion: Thalidomide, and in particular combination celecoxib-thalidomide has substantial activity in relapsed MM with prolonged PFS beyond 24m in approximately 19% of patients. The strongest predictor of prolonged PFS is β2M. The depth of response to thalidomide had little influence on predicting remission duration.

Author notes

Disclosure: No relevant conflicts of interest to declare.