February 08, 2016
2 min read

Addition of lenalidomide to standard therapy fails to prolong PFS in multiple myeloma

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Combination lenalidomide, melphalan and prednisone, followed by lenalidomide maintenance, did not significantly extend PFS or improve response rates compared with standard of care among transplant-ineligible patients with newly diagnosed multiple myeloma, according to the results of a randomized phase 3 study.

However, the novel combination appeared to reduce the rate of neuropathy, results showed.

Thalidomide (Thalomid, Celgene), melphalan (Alkeran, GlaxoSmithKline) and prednisone, followed by thalidomide maintenance, currently serves as the standard of care for patients with multiple myeloma deemed ineligible for stem cell transplantation.

However, due to the neurotoxicity associated with long-term thalidomide exposure, new treatments for transplantation-ineligible patients with multiple myeloma are needed, according to study background.

Thus, Sonja Zweegman, MD, PhD, professor of hematology at VU Medical Center in Amsterdam, and colleagues sought to evaluate the safety and efficacy of regimen that replaced thalidomide with lenalidomide (Revlimid, Celgene).

The study included data from 637 patients (median age, 73 years; range, 60-91) who received nine 4-weekly cycles of treatment until disease progression or unacceptable toxicity.

Researchers randomly assigned 318 patients to the control arm, consisting of 200 mg daily thalidomide, 0.18 mg/kg melphalan (days 1-4) and 2 mg/kg prednisone (days 1-4) during induction, followed by 100 mg daily thalidomide maintenance.

The other 319 patients received the novel combination, which replaced thalidomide with 10 mg daily lenalidomide (days 1-21) during induction and maintenance.

PFS served as the primary endpoint. Key secondary endpoints included response rate, OS and adverse events.

Median follow-up was 36 months.

Median PFS was 23 months in the lenalidomide arm vs. 20 months in the thalidomide arm (HR = 0.87; 95% CI, 0.72-1.04).

A separate analysis driven by patient age (≤ 75 years vs. ≥76 years) further demonstrated that age did not affect PFS in either arm (thalidomide arm, 20 months vs. 20 months; lenalidomide arm, 22 months vs. 23 months).

Patients in both study arms achieved similar response rates, with 47% of patients assigned thalidomide and 45% of patients assigned lenalidomide achieving a very good partial response or better.

At follow-up, 247 patients had died (thalidomide, n = 130; lenalidomide, n =117). The OS rates at 2 years (73% vs. 84%), 3 years (64% vs. 69%) and 4 years (52% vs. 56%) showed a nonsignificant trend towards improvement with lenalidomide (HR = 0.79; 95% CI, 0.61-1.01).

Safety profiles varied between the combinations. More patients assigned lenalidomide experienced hematological toxicity, especially grade 3 or worse neutropenia (64% vs. 27%; P < .001).

However, more patients assigned thalidomide experienced increased grade 3 or worse neuropathy (16% vs. 2%; P < .001), which led to a shorter duration of maintenance therapy (median, 5 months vs. 17 months).

“Because of similar efficacy of both regimens, but a pronounced difference in neuropathy, in our opinion [the lenalidomide combination] is the preferred regimen over [the thalidomide combination],” Zweegman and colleagues wrote. “However, on a global perspective, taking accessibility and costs of novel agents and the required growth factors using [the lenalidomide combination] into account, a role for [the thalidomide combination], especially in good-risk patients, remains, provided that close monitoring of the development of neuropathy and early discontinuation of thalidomide is secured.” – by Cameron Kelsall

Disclosure: Celgene provided funding for this study. Zweegman reports research funding from and consultant roles with Celgene, Janssen and Takeda. Please see the full study for a list of all other researchers’ relevant financial disclosures.