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Management of Patients with Newly Diagnosed Multiple Myeloma Highlighted at ASCO 2014

Value-Based Care in Myeloma - Multiple Myeloma
Caroline Helwick

Immunomodulating Agents Found Comparable in Melphalan-Based Regimen Lenalidomide is generally preferred over thalidomide for the treatment of patients with myeloma; however, results of the E1A06 trial showed that these 2 immunomodulating agents are comparable when used with melphalan plus prednisone in patients with newly diagnosed disease who are not eligible for transplant.

Keith Stewart, MBChB, from the Mayo Clinic, Scottsdale, AZ, presented the study of 306 patients (median age, 76 years) who were randomized to melphalan plus prednisone and 12 cycles of thalidomide (100 mg), with thalidomide continuing as maintenance (MPT-T), or to 12 cycles of lenalidomide (10 mg), with lenalidomide continuing as maintenance (MPR-R). The study had a noninferiority design with a superiority alternative.

“The findings were statistically inconclusive. The study did not prove inferiority or noninferiority of MPR-R compared to MPT-T,” said Mr Stewart.

The differences in treatment exposure did not explain the findings. There were no differences between the arms in median follow-up (approximately 41 months) and median time on therapy (12 months). Both groups received approximately 80% of the planned dose, and 46% of the patients started maintenance therapy. For patients who started maintenance treatment, the median time to therapy was 23 months.

The response rate was 75% with MPT-T and 70% with MPR-R, with very good or complete responses observed in 25% and 32% of patients, respectively.

The median progression-free survival (PFS) was 21 months in the thalidomide arm and 18.7 months in the lenalidomide arm; the median overall survival (OS) was 52.6 months versus 47.7 months, respectively; the 2-year survival rates were 78% and 72%, respectively.

The overall toxicity, however, was lower in the lenalidomide arm than in the thalidomide arm, with 58% versus 73% rates, respectively, of grade ≥3 adverse events. The nonhematologic toxicity rates were 40% versus 59%, respectively, and the patient-reported quality of life was also better with MPR-R at the end of induction, Mr Stewart reported.

These findings could possibly be explained by the fact that the outcomes in the lenalidomide arm were not as good as those seen in other similar trials, according to Mr Stewart.

Continuous Maintenance Therapy Improves Disease Progression End Points Antonio Palumbo, MD, of the University of Torino, Italy, and colleagues investigated the potential benefit of continuous maintenance therapy after intensive upfront treatment in patients with newly diagnosed myeloma. The recent FIRST trial, which was presented at a plenary session during the 2013 American Society of Hematology annual meeting, showed that continuous treatment with lenalidomide plus dexamethasone improves response rates, PFS, and OS.

At the 2014 ASCO annual meeting, Dr Palumbo presented the results of a study involving 1218 patients with newly diagnosed myeloma from 3 Italian clinical trials. Those trials evaluated 2 groups—patients receiving continuous therapy after an initial induction or consolidation therapy with either bortezomib or lenalidomide, and patients receiving fixed-dose induction or consolidation therapy without maintenance.

The investigators evaluated the time from diagnosis to the first relapse (PFS1), time from diagnosis to second relapse after second-line therapy (PFS2), and OS. They also determined second PFS, which was the time between the first relapse and the second relapse. A total of 644 patients received continuous therapy, whereas 614 patients had fixed-duration therapy.

The median PFS1 was 32 months for continuous therapy versus 16 months for fixed-duration therapy (P <.001), and all subgroups favored continuous treatment. The median PFS2 was 55 months for continuous therapy versus 40 months for fixed-duration therapy (P <.001). For second PFS, the median times were the same—15 months.

The 4-year OS rates were also improved with continuous therapy, 69% versus 60%, representing a 31% reduction of death (P = .003) with maintenance.

In a discussion of the study, Luciano Costa, MD, PhD, of the Medical University of South Carolina, Charleston, concurred that continuous therapy is best. He noted that the benefit of PFS1 with continuous therapy “permeates subsequent lines of therapy, and translates into better PFS1 and overall survival.”

This is shown, irrespective of stem-cell transplant, disease stage, risk strata, and possibly class of agent, Dr Costa said.

“Relapses are often deadly, and many patients don’t get the benefit of multiple lines of treatment,” Dr Costa pointed out. “There is no disease control penalty for the early use of active agents. The first remission is the best, the longest, and is known to affect survival.”

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Last modified: May 20, 2015
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