Lenalidomide Plus Dexamethasone Combat Smouldering Multiple Myeloma Progression

Smouldering multiple myeloma progression risk may be reduced by pre-emptive therapy

medwireNews: Long-term follow-up results from the QuiRedex trial suggest patients with high-risk smouldering multiple myeloma may benefit from early treatment.

After a median of 75 months, lenalidomide plus dexamethasone were associated with a significant progression-free survival benefit compared with observation; the median time to progression was not reached versus 23 months (hazard ratio [HR]=0.24).

Progression to multiple myeloma occurred in 39% of 57 patients given active treatment and 86% of 62 patients who were not, the investigators report in The Lancet Oncology.

At data cutoff, 18% and 36% of patients in the active and observation groups, respectively, had died. And although median overall survival from time of study entry was not reached in either group, the treatment group did have significantly longer overall survival from diagnosis to death from any cause, at a median not reached versus 117.6 months in controls.

Specifically, three of the 10 deaths in the treatment group were from disease progression, one death from respiratory infection associated with lenalidomide plus dexamethasone therapy, one associated with toxicity from rescue treatment, one from secondary malignancy and four from other causes.

By contrast, all 22 of the deaths in the observation group occurred after disease progression, with cause of death being disease progression, sudden death or surgical complications in 11, one and 10 patients, respectively. Two of the deaths from surgical complications were late events, probably related to cumulative toxicity associated with treatment, the researchers comment.

Survival among patients who received further treatment at time of progression was comparable in the active treatment and observation groups (HR=1.34), indicating that early treatment did not increase the likelihood of treatment-resistant relapse.

The most common grade 3 events in the patients given lenalidomide plus dexamethasone were infection (6%), asthenia (6%), neutropenia (5%) and skin rash (3%), all of which occurred during induction therapy.

Although there was a higher rate of second primary malignancies among patients given treatment than controls (10 vs 2%), the cumulative risk did not significantly differ.

“Overall, these findings demonstrate the relevance of a treatment approach focused on early intervention with lenalidomide plus dexamethasone for patients with high-risk disease, rather than reserving optimum treatments until the moment of progression”, write María-Victoria Mateos, from Hospital Universitario de Salamanca in Spain, and co-authors.

Heinz Ludwig, from Wilhelminen Cancer Research Institute in Vienna, Austria, writes in an accompanying comment that “Mateos and colleagues' trial of early treatment in patients with high-risk smouldering myeloma is likely to change the present strategy of no treatment.”

However, he says that the treatment combination should be confirmed in a large prospective trial and notes that monitoring patients for early signs of progression using free light chain assays might have resulted in earlier treatment and fewer toxicity-related deaths in patients who underwent observation and subsequently required rescue therapy.

“We look forward to confirmation of these results in studies applying modern criteria as outlined above”, he writes. “Until then, watchful follow-up or inclusion in one of the several ongoing trials […] remains standard.” 

References

Mateos M-V, Hernandez M-T, Giraldo P, et al. Lenalidomide plus dexamethasone versus observation in patients with high-risk smouldering multiple myelsoma (QuiRedex): long-term follow-up a randomised, controlled, phase 3 trial.Lancet Oncol 2016; Advance online publication 8 July. DOI: http://dx.doi.org/10.1016/S1470-2045(16)30124-3

Ludwig H. Early treatment for high-risk smouldering multiple myeloma: has the time come? Lancet Oncol 2016; Advance online publication 8 July. DOI: http://dx.doi.org/10.1016/S1470-2045(16)30151-6

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