Outcomes Analysis of Doublets of Novel Agents with Corticosteroids Versus Regimens with 3 or More Agents for Multiple Myeloma (MM): A Retrospective Analysis

Lenalidomide (Len) and bortezomib (Bort) have been shown to improve the outcomes of patients with MM. These novel agents have been used in combination with corticosteroids as doublets but also in combination with alkylating agents, anthracyclines and each other in more complex regimens of 3 or more agents. While more complex regimens have shown improved response rates and progression free survival compared to doublets using either of these two novel agents, it remains unclear if there is a survival advantage to the use of 3 or more agents in combination.

Patients with MM who received both Bort and Len non concurrently at our institution between January 2004 and August 2010 were included in this analysis. Patients were stratified according to whether they had received Len+/−Dexamethasone or Len in combination with 2 or more agents into Len A and Len B respectively. Similarly, Bort based therapy was stratified according to whether it was Bort+/−dexamethasone or Bort + 2 or more agents into Bort A or Bort B respectively. Finally, patients who received only doublets or single agents were thought to receive Non Intensive (NIT) therapy. Those who received 3 more agents in combination at some point were labeled to have received Intensive therapy (IT). High risk cytogenetics included deletion 13q, 17p, t(4:14), t(14;16) or hypodiploidy. The primary outcome measure was overall survival (OS) from initial diagnosis.

208 patients were confirmed to have received both Bort and Len. The median age was 60 years (range 33–80), 59% were males. Len A included 177 patients, Len B 21 patients. Bort A included 158 patients, while Bort B 49 patients. NIT included 132 patients, and IT 59 patients. No differences were noted in baseline characteristics including age, ISS and Durie/Salmon stage, baseline β2microglobulin or renal function, presence of poor risk cytogenetics, frequency of high dose therapy between Bort A and B, Len A and B or the IT arm or NIT groups respectively. Bort B patients were more likely to have bone disease (82 versus 65%, p=0.03) than Bort A patients. Len A patients had a trend toward improved OS as compared to Len B (median OS 72 vs 57 months, p=0.07). Bort A patients had an improved OS compared to Bort B (median OS 72 vs 45 months, p= 0.02). Similarly NIT patients had improved OS compared to IT (median OS 74 vs 57 months, p=0.03). In addition, patients without poor risk cytogenetics, did not have differences in OS regardless of whether they belonged to the IT or NIT groups. However patients who had poor risk cytogenetics, had a worse survival if they belonged to the IT group compared to the NIT (median OS 46 vs 71 months, p=0.01). On multivariable analysis, only the presence of renal failure at baseline and the IT group were negative prognostic factors.

This retrospective analysis suggests that a sequence of doublets is associated with improved survival among patients with myeloma as compared to regimens with 3 or more agents in patients with high risk cytogenetics. While the limitations of this retrospective study limit drawing definitive conclusions, it appears that poor cytogenetics and disease biology trumps treatment intensification.

Baz:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millenium: Research Funding. Alsina:Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Allergan: Research Funding. Djulbegovic:Millenium: Research Funding.