Trial Data Supports Darzalex Combo as Potentially Effective in Myeloma Patients Who Don’t Respond to Revlimid

José Lopes, PhD avatar

by José Lopes, PhD |

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TAK-169 trial first patient dosed

A combination of Darzalex (daratumumab) plus Kyprolis (carfilzomib) and dexamethasone is well-tolerated and may be effective in multiple myeloma patients who fail to respond to treatment with Revlimid (lenalidomide), data from a Phase 1b study suggests.

Janssen will present updated data from its MMY1001 study (NCT01998971) at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, set for June 1-5 in Chicago.

The presentation, “Daratumumab (DARA) in combination with carfilzomib and dexamethasone (D-Kd) in lenalidomide (Len)-refractory patients (Pts) with relapsed multiple myeloma (MM): Subgroup analysis of MMY1001” takes  place on Friday, June 1, as part of the Hematologic Malignancies–Plasma Cell Dyscrasia session.

The ongoing MMY1001 study is evaluating the safety, tolerability, and dosing regimens of Darzalex in combination with various other medications for the treatment of myeloma. This data update examined the safety and efficacy of a combo including Darzalex, Kyprolis and dexamethasone in relapsed myeloma patients whose disease is refractory to Revlimid. This patient population typically has poor outcomes.

Scientists enrolled a total of 85 patients who had received one to three prior lines of therapy, but not Kyprolis. They were given Kyprolis on days 1, 8 and 15 of 28-day cycles. Kyprolis’ dose was 20 mg/m2 on the first day of treatment, and 70 mg/m2 thereafter, while that of dexamethasone was 40 mg once weekly

Darzalex was given once weekly in the first two cycles, every two weeks in cycles three to six, and then every four weeks. Ten patients received a standard 16 mg/kg dose of Darzalex on the first day of treatment, while 75 were given a split 8 mg/kg first dose on days one and two of treatment.

Among these 85 patients, 51 were refractory to Revlimid and had a median age of 66 years (range 38-85). Patients refractory, or unresponsive, to treatment are those showing disease progression at or earlier than 60 days of completing the last line of therapy.

Among prior treatments given, 98 percent of patients had used Velcade (bortezomib), 18 percent Pomalyst (pomalidomide), 43 percent were refractory to Velcade, and 18 percent to Pomalyst.

Twenty patients had to discontinue treatment due either to progressive disease, adverse events, patient withdrawal, or physician decision.

The most frequent blood-related severe or life-threatening adverse events were low platelet counts, anemia, low levels of neutrophils, and low white blood cell counts. Infusion-related reactions occurred in 37 percent of patients, but none were severe.

Response to treatment was seen in 86 percent of all patients, and in 81 percent of those refractory to Revlimid. Most were very good partial responses — deep responses to therapy although some residual markers of myeloma were still present.

These response rates are similar to those seen in myeloma patients treated with an approved regimen of Pomalyst, Velcade, and dexamethasone.

Progression-free survival, which is the length of time during or after treatment without cancer progression, was 14.1 months. The PFS rate at 12 months was 69%.

“The combination of [Darzalex] and weekly [Kyprolis+dexamethasone] was well tolerated and demonstrated promising efficacy,” the investigators wrote.

The U.S. Food and Drug Administration (FDA) approved a combination of Darzalex, Pomalyst and dexamethasone to treat certain refractory multiple myeloma patients in June 2017. The FDA had previously approved Darzalex as a stand-alone therapy for myeloma patients who received at least three lines of treatment. Combinations of Darzalex with Revlimid and dexamethasone, and another with Velcade and dexamethasone, have also been approved for previously treated patients.