medwireNews: Patients with multiple myeloma derive continued long-term benefit from lenalidomide maintenance after autologous stem-cell transplantation (ASCT), shows an updated analysis of phase III CALGB (Alliance) 100104 trial data.
However, the previously reported increased risk for hematologic second primary malignancies in patients receiving this treatment was also maintained, Philip McCarthy (Roswell Park Cancer Institute, Buffalo, New York, USA) and co-authors report in The Lancet Haematology.
In spite of this, the researchers say that the benefits outweigh the risks and therefore lenalidomide maintenance after ASCT until disease progression should be considered “a standard of care.”
At a median follow-up of 91 months, 146 (63%) of 231 patients with newly diagnosed myeloma who were randomly assigned to receive post-ASCT maintenance therapy with lenalidomide 10–15 mg daily had progressive disease or had died, compared with 176 (77%) of 229 patients who received placebo.
The risk for disease progression was a significant 43% lower in the lenalidomide than in the placebo group, with median progression-free survival times of 57.3 versus 28.9 months.
Mortality rates were also lower among the patients receiving lenalidomide compared with those receiving placebo, at 38% versus 52%. The corresponding median overall survival times were 113.8 versus 84.1 months, a difference that was statistically significant and gave a hazard ratio of 0.61 in favor of lenalidomide.
But grade 3 or worse adverse events were more common with lenalidomide than with placebo. For example, 50% of patients receiving lenalidomide experienced neutropenia compared with 18% of those receiving placebo, while 15% versus 5% had thrombocytopenia.
Hematologic, solid tumor, and noninvasive second primary malignancies were also more common with lenalidomide, occurring at rates of 8%, 6%, and 5%, respectively, versus 1%, 4%, and 3% with placebo.
And the researchers point out that all of the hematologic tumors, approximately half (56%) of the solid tumors, and 83% of the second primary malignancies that developed in patients assigned to the placebo group occurred in those who crossed over to lenalidomide at unblinding, after a median of 18 months (n=86).
McCarthy et al conclude that “although lenalidomide maintenance is associated with an increased risk of both haematological and solid-tumour second primary malignancies, the risk is offset by the magnitude of the benefits in time to progression and overall survival.”
They add: “Lenalidomide maintenance until progression after ASCT might be considered a standard of care and should form the backbone of future maintenance studies incorporating novel drugs, such as monoclonal antibodies or vaccine-based approaches.”
Commenting on the findings, Mario Boccadoro, from the University of Turin in Italy, says that while “the balance of risk to benefit was clearly in favour of the maintenance treatment,” it is unclear which patients will benefit most and what the optimum duration of lenalidomide maintenance would be.
He suggests that measuring minimal residual disease, a “potentially important clinical endpoint in multiple myeloma,” could help “to answer the many questions raised by maintenance therapy in the near future.”
By Laura Cowen
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