Superior 12-yr Survival (66% vs 30%) with 5-yr Continuous (Rc) vs “Discontinuous” Remission (Rd): Results of Total Therapies 1 & 2 (TT1,2) for Multiple Myeloma (MM).

Background: The extension of overall survival (OS) in MM has been partly linked to increasing CR rates especially with high-dose melphalan. Data bases of TT1 and TT2 were examined to determine whether 5-yr Rc was key to prolonged OS.

Patients and Methods: TT1 enrolled 231 and TT2 668 patients (median follow-up, 4 years). Pre-study characteristics of Rc vs Rd patients surviving >= 5yrs were compared. Furthermore, subsequent OS was examined in the context of pre-treatment variables, TT2 vs TT1 and Rc vs Rd. Only those Rd patients who were event-free (CR or PR) at least 1 year prior to the 5-yr landmark were included in this analysis.

Results: Among 231 TT1 + TT2 patients surviving >= 5yrs, more TT2 patients were Rc compared to Rd (60% vs 19%, p<0.001) and more older patients were Rc (at least 65: 13% vs 3%, p=0.019). Importantly, baseline LDH, B2M, CRP, albumin, presence of cytogenetic abnormalities (CA) and whether thalidomide was part of TT2 were evenly distributed among Rc and Rd groups. Furthermore, the 5-yr risk profile of Rc patients was lower than that of Rd patients: lower bone marrow plasma cell % (at least 33%: 0% vs 14%, p=0.003), higher albumin (less than 3.5g/dL: 7% vs 16%, p=0.047), higher Hb (less than 10g/dL: 4% vs 16%, p=0.023), less frequent CA13 (1% vs 11%, p=0.007). Rc patients had significantly longer subsequent survival than those with Rd (12-year survival from enrollment and 7 yrs post-landmark: 66% vs 30%, p<0.001) (Figure). In addition to Rc, univariately significant factors for post 5-year OS were data at 5 years on CA, albumin, B2M, CRP and creatinine. Rc and no CA at 5yrs were the key factors favoring long subsequent survival; thus, 12-yr OS rates decreased from 57% in the 94 patients with Rc/noCA to 44% in 44 with noRC/noCA; 8 of 9 noRc/CA patients have died by year eight; 1 of the 8 Rc/CA patients has died.

Conclusion: 5-yr Rc appears to be an important prerequisite for prolonged subsequent OS, which could be significantly increased with better therapy (TT2 vs TT1). Post-5-yr favorable survival predictors included several laboratory data at 5yrs, especially absence of CA.

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Overall Survival from 5 Years Post Enrollment by Remission Status at 5 Years (Interrupted vs Continuous Remisssion)

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Overall Survival from 5 Years Post Enrollment by Remission Status at 5 Years (Interrupted vs Continuous Remisssion)

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