Thalidomide-Dexamethasone (Thal-dex) vs Interferon-α-Dexamethasone (IFN-dex) as Maintenance Treatment after ThaDD Induction for Multiple Myeloma (MM): First Analysis of a Prospective Randomized Study.

Despite the improvements in the treatment of MM patients, they ultimately progress and die of their disease since all attempts to control residual disease with a maintenance therapy have substantially failed in providing significant results. Nevertheless, maintenance therapy may still be an appealing approach.

We treated 120 de novo or relapsed/refractory MM patients with Thalidomide, Dexametasone and peghilated liposomal Doxorubicin (ThaDD) as induction treatment of de novo or relapsed/refractory MM. All patients achieving at least minor response were randomized to receive Thalidomide 100 mg continuously or IFN-α 3 MU three times per week subcutaneously until the occurrence of relapse or major toxicities. Both drugs were combined with oral 20 mg Dexamethasone for 4 days monthly. In the original protocol an interim analysis was planned after a median follow-up of two years in order to assess a unacceptable imbalance between the two treatment arms leading to a premature interruption of protocol.

At this moment, 74 patients are evaluable for maintenance therapy, 36 in the Thal-dex arm and 38 in the IFN-dex arm. The two groups of patients were matched on the basis of the main prognostic factors as age, serum β2-microglobulin, serum albumin, ISS score, CRP, cytogenetics and response to therapy. IFN-dex and Thal-dex improved response in 13% and 17% of patients, respectively (p=0.532) whereas rate of progression (58% vs 36%; p=0.0061) and mortality (42% vs 19.5%; p=0.035) were significantly higher in the IFN-dex arm. After a median 24 months follow-up, median TTP was 21 months and 2 years TTP was 45% in the IFN-dex arm vs Thal-dex arm whereas median was not reached and 2 years TTP was 59% (p=0.0139). A clear better OS trend was observed in the Thal-dex arm when compared with IFN-dex arm (2-yrs OS 84% vs 71%; p=0.0821). Multivariate analysis found serum CRP ≤ 3 mg/l, not unfavourable cytogenetics, response to induction ≥ VGPR and maintenance with Thal-dex significantly associated with better TTP. Both treatment arms were overall well tolerated: fever, anorexia, weight loss, fatigue, liver and heart function abnormalities and hematologic toxicities were significantly more frequent in the IFN-dex arm whereas neurotocity (somnolence, constipation and peripheral neurophaty) were somewhat more frequent in the Thal-dex arm. This turned into a rate of therapy reduction and interruption significantly higher in the IFN-dex arm than in the Thal-dex one (23% vs 5%; p=0.0231).

In conclusion, our data show that in MM patients the combination Thal-dex administered as maintenance therapy after thalidomide, dexamethasone and chemotherapy combination, although it does not significantly improve the quality of response obtained after induction therapy, is significantly better in controlling residual disease than the IFN-dex combination which, on the other hand, leads more frequently either to systemic side effects or organ toxicity.