Carfilzomib, Lenalidomide, Dexamethasone Trio Promising in Multiple Myeloma

Patients with newly diagnosed multiple myeloma as well as those with asymptomatic disease may benefit from the combination of carfilzomib, lenalidomide and dexamethasone

medwireNews: The triad of carfilzomib, lenalidomide and dexamethasone is well tolerated and elicits deep responses in multiple myeloma patients, research shows.

The findings suggest that not only patients with newly diagnosed disease, but also those with high-risk smouldering or asymptomatic multiple myeloma could benefit from the combination.

Enrolled patients were given the selective proteasome inhibitor carfilzomib initially at 20 mg/m2 on days 1 and 2 of cycle 1 and 36 mg/m2 thereafter, lenalidomide 25 mg/day and dexamethasone at a dose of 20 mg/day during cycles 1 to 4 and 10 mg/day during cycles 5 to 8. Those with at least stable disease after eight treatment cycles went on to receive lenalidomide for 2 years.

No patient experienced peripheral neuropathy of grade 3 or higher, one of the primary endpoints of the study.

Lymphopenia was the most frequent adverse event of grade 3 or 4 in both sets of patients, followed by electrolyte or metabolism abnormalities in those with newly diagnosed disease and skin abnormalities in those with asymptomatic disease.

After a median follow-up of 17.3 months, a complete response (CR) or stringent CR was observed in 56% of 45 patients with newly diagnosed multiple myeloma, with 7%, 27% and 9% achieving a near CR, very good partial response (PR) and PR, respectively.

And CRs or stringent CRs were observed in all 12 participants with smouldering multiple myeloma after a median of 15.9 months of follow-up.

Treatment with the study regimen led to an absence of minimal residual disease (MRD), as assessed by multiparametric flow cytometry, in all 28 newly diagnosed multiple myeloma patients with a best overall response of at least a near CR and in 92% of the 12 patients with asymptomatic disease.

When evaluated by next-generation sequencing, MRD negativity was seen in 67% of 21 newly diagnosed patients with at least a near CR who had available samples and in 75% of 12 participants with smouldering disease.

Progression-free survival probability at 12 months was significantly better for MRD-negative patients than MRD-positive patients, whether assessed by multiparametric flow cytometry or next-generation sequencing, at 100% versus 79% and 100% versus 95%, respectively.

“Taken together, our results provide further evidence for the role for proteasome inhibitor–immunomodulatory drug combination therapy in [newly diagnosed multiple myeloma] and demonstrate that MRD evaluation may be an important tool for measuring the depth of response”, conclude Ola Landgren, from Memorial Sloan Kettering Cancer Center in New York, USA, and colleagues in JAMA Oncology.

They add that “the pilot study in high-risk [smouldering multiple myeloma] provides proof of principle to support future large-scale trials of tolerable regimens capable of achieving high rates of sustainable MRD-negative responses in this population.”

Reference

Korde N, Roschewski M, Zingone A, et al. Treatment With Carfilzomib-Lenalidomide-Dexamethasone With Lenalidomide Extension in Patients With Smoldering or Newly Diagnosed Multiple Myeloma. JAMA Oncol 2015; Advance online publication 2 July. doi:10.1001/jamaoncol.2015.2010

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