medwireNews: Combination therapy with lenalidomide, bortezomib, and dexamethasone (RVD) plus transplantation halts disease progression more effectively than drug treatment alone in patients with newly diagnosed multiple myeloma, study findings indicate.
However, Michel Attal (Institut Universitaire du Cancer de Toulouse-Oncopole, France) and co-researchers caution that the “benefit must be weighed against the increased risk of toxic effects associated with high-dose chemotherapy plus transplantation, especially since we found that later transplantation might be as effective as early transplantation in securing long-term survival.”
The IFM 2009 study investigators randomly assigned 700 patients, aged 65 years and older, with newly diagnosed multiple myeloma to receive induction therapy with three cycles of RVD and then consolidation therapy with either five additional cycles of RVD (n=350) or high-dose melphalan plus stem-cell transplantation followed by two additional cycles of RVD (n=350). Patients in both groups received maintenance therapy with lenalidomide for 1 year.
As reported in The New England Journal of Medicine, disease progression or death occurred in 157 patients in the transplantation group and 211 in the RVD-alone group during a median follow-up of 43 and 44 months, respectively.
Patients who underwent transplantation had a significant 35% reduced risk for disease progression or death than those who did not, with respective median progression-free survival times of 50 and 36 months.
The complete response rate was also significantly higher in the transplantation group than in the RVD-alone group (59 vs 48%), as was the proportion of patients with no minimal residual disease detected (79 vs 65%).
By contrast, overall survival at 4 years did not differ significantly between the two groups, at 81% with transplantation and 82% without it.
Attal and co-authors suggest that this might be due to the fact that both treatment groups received RVD therapy or may be down to the successful use of salvage transplantation, which was used in 136 of 207 patients in the RVD-alone group who had disease progression.
The researchers also note that overall survival was significantly longer among patients with no minimal residual disease compared with those in whom it was detected, regardless of the treatment they received.
Although survival outcomes were better in the transplantation group, these patients also had higher rates of grade 3 or 4 adverse events than those in the RVD-alone group, including neutropenia (92 vs 47%), gastrointestinal disorders (28 vs 7%), and infections (20% vs 9%).
Attal et al conclude: “Our results suggest that the use of a combination therapy that incorporates newer proteasome inhibitors, next-generation immunomodulatory drugs, and potent monoclonal antibodies along with transplantation tailored according to minimal residual disease detection could further improve outcomes among adults up to 65 years of age who have multiple myeloma.”
In an accompanying editorial, Charles Schiffer and Jeffrey Zonder, both from Wayne State University School of Medicine in Detroit, Michigan, USA, say; “The observed lack of a survival benefit for early transplantation was consistent with previous results that suggested salvage transplantation is an equalizer in this regard.”
Therefore it remains unclear “as to whether all patients with multiple myeloma should undergo immediate autologous stem-cell transplantation,” they write.
By Laura Cowen
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