Lenalidomide ‘best maintenance option’ for multiple myeloma

Lenalidomide maintenance improved PFS and OS among patients with newly diagnosed multiple myeloma compared with other maintenance treatments, according to results from a network meta-analysis.

“The continuous therapy approach has been evaluated extensively in patients with newly diagnosed multiple myeloma, across age groups and treatment strategies upfront, in several trials with different designs,” Francesca Gay, MD, PhD, hematologist at the myeloma unit of the Azienda Ospedaliero-Universitaria Città della Salute e della Scienza in Italy, and colleagues wrote. “It generally consists of multiagent chemotherapy for a fixed time, followed by a less intensive but prolonged maintenance treatment.

“Despite the well-recognized importance of maintenance, there is no evidence demonstrating the overall superiority of regimen over the others, owing to the lack of direct or indirect comparisons,” they added.

To assess the best maintenance treatment, Gay and colleagues performed two searches in PubMed and Cochrane databases and identified 11 phase 3 randomized trials published from 1999 to November 20, 2017. The trials evaluated at least two novel agent-based maintenance treatments among patients with newly diagnosed multiple myeloma.

Comparators in the trials included placebo and no maintenance; however, to allow comparison of all treatments, researchers selected no maintenance as the common comparator, assuming the effect of placebo was the same as no treatment.

Researchers excluded trials in which patients who received two different maintenance treatments underwent different and noncomparable premaintenance therapies and trials that enrolled

only patients who did not receive novel agents during induction.

The 11 trials evaluated eight maintenance options, including no maintenance/placebo, interferon, thalidomide alone, thalidomide-bortezomib, thalidomide-interferon, lenalidomide (Revlimid, Celgene) alone, lenalidomide-prednisone and bortezomib-prednisone.

The analysis included 5,073 patients with newly diagnosed multiple myeloma.

Lenalidomide-based regimens appeared to have the best outcomes on PFS analysis (lenalidomide-prednisone, HR = 0.39; 95% CI, 0.28-0.53; lenalidomide alone, HR = 0.47; 95% CI 0.39-0.55).

These treatments showed a median ranking distribution of one for lenalidomide-prednisone and two for lenalidomide alone out of all the maintenance regimens. They resulted in being the best treatment options in 74% of simulations.

Thalidomide-interferon, thalidomide-bortezomib, bortezomib-prednisone and thalidomide alone all showed HRs in favor of PFS benefit as maintenance therapies (HR range, 0.5-0.73). Interferon alone did not show any benefit.

When evaluating OS, lenalidomide alone appeared to be the best treatment option (HR = 0.76; 95% CI, 0.51-1.16). Lenalidomide alone had a median ranking distribution of one and a 38% probability of being the best treatment.

Bortezomib-thalidomide and bortezomib-prednisone appeared to be the next best treatment options. Investigators did not observe benefit with the other regimens.

In a subgroup analysis, lenalidomide-based maintenance appeared to be the best option for patients with good prognosis (stage I or stage II disease, n = 2,144) and patients with standard-risk chromosomal abnormalities (n = 1,657). Among patients with poor prognosis (stage III disease, n = 626), bortezomib-based maintenance appeared to be the best treatment option.

“Results of analysis suggested that lenalidomide was the best maintenance option,” the researchers wrote.

The limitations of the study included the assumption that placebo would have the same effect as no maintenance; the lack of distinguishing between maintenance therapy doses; and no reporting on adverse events, drug discontinuations and quality of life.

“Despite the assumptions and limitations of this network meta-analysis, our results support the use of lenalidomide maintenance therapy in most patients,” the researchers wrote. “Still, better treatment options are required in patients with aggressive disease, who may benefit from combinations of proteasome inhibitors and immunomodulatory agents. There are ongoing trials evaluating maintenance therapy with second-generation proteasome inhibitors alone or plus immunomodulatory agents and with monoclonal antibodies.” – by Cassie Homer

Disclosures: Gay reports honoraria from Amgen, Bristol-Myers Squibb, Celgene, Takeda and Janssen and advisory board roles with Celgene, Roche, Seattle Genetics and Takeda. Please see the study for all other authors’ relevant financial disclosures.