In older, intermediate-fit patients newly diagnosed with multiple myeloma and receiving lenalidomide-dexamethasone (Rd) therapy, lenalidomide can be safely reduced and dexamethasone eliminated following induction therapy, a new study from Italy suggests. The adjusted treatment regimen (Rd-R) significantly lengthened event-free survival, without compromising progression-free or overall survival, after induction therapy consisting of nine 28-day cycles of Rd, researchers report in Blood. Patients with multiple myeloma usually receive continuous treatment including steroids, which are typically given until a patient's disease progresses or they can no longer tolerate the therapy, lead author Dr. Alessandra Larocca, of the University of Turin, said in a press release. She added, "Prolonged steroid use is scarcely tolerated in the long term, even in younger patients, and patients may often require dose reduction or interruption." Long-term use of regimens incorporating dexamethasone has been associated with insomnia, anxiety, agitation, weight gain, osteoporosis and leg edema. Dr. Larocca and her colleagues conducted a phase-3 trial, purportedly the first of its kind, to compare the Rd-R regimen with standard continuous Rd in patients newly diagnosed with multiple myeloma who were not eligible for autologous stem-cell transplantation. The researchers enrolled 199 patients between ages 65 and 80 (median age, 76) at 33 centers in Italy; the participants were neither fit nor frail, as rated on the International Myeloma Working Group frailty scale. The 98 patients randomized to continuous Rd received 28-day cycles of lenalidomide (25 mg per day for 21 days) and dexamethasone (20 mg on days 1, 8, 15, and 22) till progression or intolerance. The 101 patients randomized to Rd-R received induction therapy of nine 28-day cycles as described above. This was followed by only lenalidomide maintenance (10 mg per day for 21 days) till progression or intolerance. Seventy patients died (32 on Rd-R and 38 on Rd) over a median follow-up of 37 months, 15 in each group because of progressive disease. Median event-free survival was 10.4 months in the Rd-R arm and 6.9 months in the Rd arm (P=0.02), progression-free survival was 20.2 versus 18.3 months (P=0.16) and three-year overall survival was 74% versus 63% (P=0.06). The rate of lenalidomide discontinuation because of adverse events was 24% with Rd-R versus 30% with continuous Rd. At the time of analysis, 58 patients were still receiving therapy: 34 on Rd-R and 24 on Rd. The findings could have important implications for practice, said Dr. Larocca, who estimated that about one-third of myeloma patients who are not eligible for stem-cell transplantation fit the criteria used in this study. "We expect the results of this study may help to improve and optimize the treatment of elderly patients who may be at greater risk of treatment toxicity and poor survival due to their age or comorbidities," she said. The authors note that treatments based on monoclonal antibodies, such as daratumumab, plus Rd or VMP (bortezomib-melphalan-prednisone) have recently become standards of care. Dr. Thierry Facon, head of the Blood Diseases Service at Centre Hospitalier Regional Universitaire de Lille, in France, told Reuters Health by email that the emergence of such therapies "will not reduce the relevance of (the new) findings. In contrast, it may amplify the possibility and the interest to further reduce dexamethasone." In other words, explained Dr. Facon, who was not involved in the research, if you use Rd, you can discontinue dexamethasone after nine months (per the Italian findings). But if you use lenalidomide and daratumumab, you might discontinue dexamethasone earlier, thus retaining efficacy while having fewer dexamethasone-related adverse events. Dr. Robert A. Vescio, medical director of the Multiple Myeloma and Amyloidosis Program at Cedars-Sinai Cancer, in Los Angeles, told Reuters Health by email, "This study suggests that long-term steroid usage may not be helpful or needed. It will make me more likely to stop steroids in patients who are having side effects from them." "It should be noted," he continued, "that more people stopped lenalidomide in the continuous steroid usage arm. The use of steroids may make the patient's ability to tolerate lenalidomide more challenging, and lowering or discontinuing lenalidomide early may be of greatest detriment to their outcomes." Dr. Vescio also was not involved in the study. —Scott Baltic Source
