Triplet Combo Yields Significant Efficacy in Certain Patients With Lenalidomide-Refractory MM

A triplet combination therapy comprising carfilzomib, lenalidomide, and dexamethasone has shown significant efficacy in patients with multiple myeloma (MM) that is relapsed or refractory to all available therapies, including lenalidomide.

“Carfilzomib is an epoxyketone proteasome inhibitor of second generation, proved to be effective and safe in relapsed and refractory MM (rrMM), in combination with dexamethasone or lenalidomide and dexamethasonem” wrote Claudio Cerchione, MD, PhD, Hematology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola, Italy, and co-investigators.

A total of 41 patients with rrMM refractory to lenalidomide previously given several lines of therapy (median age at diagnosis, 63.7 years) were included in this retrospective observational trial by Dr Cerchione, et al.

These patients received carfilzomib plus lenalidomide and dexamethasone for a median of 8 treatment.

According to the investigators, ISS was equally distributed, and all patients had previously received bortezomib and immunomodulatory drugs, and were refractory to these drugs. In addition, approximately 60% had undergone at least a single autologous stem cell transplantation (SCT).

After a median follow-up of 9 months, the overall response rate was 68.2%, with 5 reports of progressive disease and 8 patients with stable disease as per International Myeloma Working Group criteria.

“This can be considered as an impressive result in this subset of rrMM patients, refractory to lenalidomide,” the researchers wrote.

Of note, for 11 patients who achieved at least a partial response, carfilzomib plus lenalidomide and dexamethasone was a bridge to second or third autologous SCT. The median time to response was 1.3 months, the median overall survival from diagnosis was 62 months, and the median overall survival from start of carfilzomib therapy was 11 months.

Carfilzomib was observed to be well-tolerated, yielding manageable grade 2 anemia in 39% of patients; grade 3-4 neutropenia in 29% of patients; and grade 2, grade 3, and grade 4 thrombocytopenia in 34%, 21%, and 12% of patients.

Furthermore, 39% of patients had pneumonia that was treated with antibiotics and always resolved, and cardiac monitoring performed in all patients showed that 34% had grade 2-3 hypertension and 39% had fatigue.

“Carfilzomib plus lenalidomide and dexamethasone has shown significant efficacy in a particularly severe setting of patients, relapsed and refractory to all available therapeutic resources, also lenalidomide, and it could be considered as a bridge to a second autologous or allogenic SCT,” Dr Cerchione and colleagues concluded.—Hina Porcelli

Cerchione C, Martinelli G, Catalano L. Carfilzomib-Lenalidomide-Dexamethasone in the Management of Lenalidomide-Refractory Multiple Myeloma. Presented at: the Lymphoma, Leukemia & Myeloma Congress; October 21-24, 2020; virtual. Abstract P-06