ROME, ITALY — Whether or not to continue drug treatment in myeloma patients who have achieved complete response to induction therapy is still debated among experts, but new results from a pooled analysis of five large studied should settle the question — it found that maintenance therapy significantly improves overall survival.
Several previous studies have shown prolonged progression-free survival (PFS) with maintenance therapy in patients showing complete response to first-line treatment. But there have been conflicting data about the impact on overall survival, leaving the question open of whether or not to continue treatment in patients with drug-sensitive disease.
Reported for the first time here at the 15th International Myeloma Workshop, a pooled analysis clarifies the role of maintenance treatment in patients showing complete response to induction therapy, including those eligible for autologous stem-cell transplantation as well as those who are not.
Presenting the data at a poster session, Chiara Cerrato, MD, research fellow in hematology at the University of Turin, Italy, said, "The role of maintenance therapy in multiple myeloma has been the object of debate. But our study finds it's really important to go on with treatment, with a difference in overall survival and progression-free survival in all patients with drug-sensitive disease."
Analysis of Pooled Data From Five Trials
Researchers from around the world pooled data from five phase 3 studies investigating different induction and maintenance treatment regimens in patients newly diagnosed with myeloma.
Three of the trials included patients eligible for autologous stem-cell transplantation:
The pooled analysis also included two studies in elderly patients ineligible for autologous stem-cell transplantation:
The researchers' primary objective was to evaluate the impact of maintenance therapy on PFS and overall survival in patients who showed complete response to their induction therapy.
Results for a total of 2792 patients were analyzed retrospectively, including 2330 who had received maintenance therapy. Just over one in five of these patients (21%) achieved complete response to induction therapy (378 patients eligible for transplant and 125 patients not eligible) before going on to maintenance treatment.
Clear Increase in PFS With Maintenance Therapy
After a median follow-up of 45 months, 5-year overall survival was significantly higher in patients receiving maintenance therapy compared with those who did not. Nearly three quarters of patients who continued treatment after complete response to their induction therapy were alive at 5 years compared with just over half of those not given maintenance therapy (74% vs 55%; hazard ratio (HR), 0.55; P < .02).
Five-year PFS was also much higher in patients given maintenance therapy (47% vs 19%; HR, 0.47; P < .001).
The researchers saw a significant benefit with maintenance therapy across all subgroups, including those eligible for autologous stem-cell transplantation (median PFS 62 vs 33 months; HR, 0.19; P = .003), and in both young patients (< 65 years) given conventional chemotherapy (not reached vs 13 months; HR, 0.17; P < .001) and elderly patients (> 65 years) treated with conventional chemotherapy (52 vs 27 months; HR, 0.57; P = .009).
Increased Survival in Elderly Patients
The researchers also found a significant overall survival advantage in elderly patients treated with conventional therapy followed by maintenance therapy (78% vs 52%; HR, 0.52; P = .03).
No significant difference in overall survival was seen in young patients who were eligible for transplant, but Dr Cerrato explained that this was because the follow-up was not yet long enough.
"Our results show that maintenance treatment prolongs progression-free survival regardless of age and type of treatment in patients showing complete response to induction therapy," she told Medscape Medical News. "We also see a clear improvement in overall survival with maintenance therapy in elderly patients. Longer follow-up will clarify if this also occurs in younger patients."
Dr Cerrato reported that current practice at her clinic in Turin is to continue drug treatment in patients with complete response to their first-line therapy. "We go on treating a patient as long as their drug treatment is well tolerated," she said. She commented that previous doubts about the benefit of maintenance therapy, as well as costs, may mean that this has not previously been standard clinical practice everywhere.
Commenting on the findings to Medscape Medical News, Charlotte Pawlyn MBBCh, Wellcome Trust Clinical Research Fellow at the Institute of Cancer Research and the Royal Marsden Hospital NHS Foundation Trust, London, United Kingdom, said, "We now have a growing number of studies showing that ongoing therapy is beneficial."
Dr Pawlyn considered that maintenance therapy is likely to become standard practice in the future because of the evidence of improved outcomes." However, she warned that not all healthcare providers currently reimburse maintenance therapy. The costs of these therapies can add up, and a recent studyfound that even myeloma patients with insurance had to use savings to pay for treatment.
David H. Vesole, MD, PhD, cochief of the Myeloma Division at John Theurer Cancer Center in Hackensack, New Jersey, cautioned that because the pooled analysis did not include crossover of patients from nonmaintenance to maintenance therapy, or vice versa, in his opinion it did not prove a difference in overall survival.
"Unless the patients who did not receive continuous therapy received the same drugs as those who did, you cannot interpret the [overall survival] benefit," he told Medscape Medical News. He added, "The current approach in myeloma is to continue therapy indefinitely — until progression or intolerance."
Dr Cerrato disclosed no relevant financial relationships. Dr Pawlyn reported receiving conference travel support from Novartis, Celgene, and Janssen. Dr Vesole has received honoraria related to speakers' bureau activities from Celgene and Millennium/Takeda.
International Myeloma Workshop 2015: Abstract BP-017, presented September 24, 2015.
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