AT ASH 2016

SAN DIEGO (FRONTLINE MEDICAL NEWS) – Maintenance therapy with lenalidomide significantly improved progression-free survival in patients of all ages with myeloma, regardless of their risk or response status at the end of induction, Gareth Morgan, MD, PhD, said during an oral session at the annual meeting of the American Society of Hematology.

“The very important point is that maintenance therapy with lenalidomide worked across a range of different risk groups,” said Dr. Morgan, director of the Myeloma Institute at the University of Arkansas for Medical Sciences in Little Rock. “It worked independent of gender, age, [International Staging System] disease stage, and response at baseline,” he added. ‘It also worked irrespective of genetic risk status, which is contrary to what you hear very frequently. All of the curves are consistent with better outcomes if you continue lenalidomide long-term.”

This phase III, multicenter, open-label Myeloma XI trial included 1,551 patients newly diagnosed with multiple myeloma who were randomly assigned to maintenance lenalidomide or observation only after completing standard induction regimens.

In the overall cohort analysis, half of the patients who received lenalidomide (Revlimid) maintenance were alive and progression-free after 36 months (95% confidence interval, 31-39 months), twice the median PFS of observation-only patients, for a hazard ratio of 0.45 (95% CI, 0.39-0.52; P less than .0001).

This effect held up across numerous subgroups. For example, among 828 transplant-eligible patients, median PFS was 50 months with lenalidomide maintenance and 28 months with observation only (HR, 0.47; P less than .0001). Among 724 transplant-ineligible patients, median PFS was 24 months with lenalidomide and 11 months with observation only (HR, 0.42; P less than .0001), Dr. Morgan reported.

Lenalidomide maintenance did not fully overcome the effects of high-risk cytogenetics but still increased PFS by a median of 10 months, compared with no maintenance (median PFS, 23 months vs. 13 months, respectively; P less than .0001). For patients with standard-risk cytogenetics, median PFS was 44 months on lenalidomide maintenance and 25 months otherwise (P less than .0001).

When patients had minimal residual disease after induction, their median PFS on lenalidomide was 17 months longer if they received maintenance lenalidomide (30 vs. 13 months; P less than .0001). Not surprisingly, the best overall outcomes occurred in MRD-negative patients who received lenalidomide maintenance (median PFS, 44 months, vs. 31 months without lenalidomide; P less than .0001), he said.

Responses also were more likely to deepen over time if patients received lenalidomide maintenance (HR, 1.74; 95% CI, 1.2-2.6; P = .004). “This continued down to about 24 months, which is compatible with conventional response rates,” Dr. Morgan noted.

Safety results reflected prior studies and were unremarkable, he added. “I treat a lot of people with lenalidomide for long periods of time, and the worst thing I usually see is some fatigue.” About one-third of patients developed grade 3-4 neutropenia on lenalidomide maintenance, but less than 5% developed grade 3-4 thrombocytopenia, anemia, deep vein thromboses, or neuropathies. Rates of primary and second malignancies were no worse with maintenance than without it. “All investigators are now in agreement on this finding,” Dr. Morgan emphasized.

The researchers also performed a whole exosome study of 70 paired specimens collected when patients were randomized and again when they relapsed. They found no evidence that lenalidomide induced excess mutations and no significant difference between groups in mutational patterns or genomic copy number variants that alter risk status.

Dr. Morgan and his associates will present overall survival data when the number of events reaches 458, he said. For now, the PFS data reinforce lenalidomide as the standard of care for patients of all ages with newly diagnosed multiple myeloma, he concluded.

The Myeloma XI trial is funded by Cancer Research UK, the Experimental Cancer Medicine Centre, NIHR Clinical Research Network: Cancer, and the University of Leeds. Dr. Morgan disclosed consulting and other relationships with Celgene, the maker of lenalidomide.


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