Conference Coverage

Daratumumab plus carfilzomib/dexamethasone effective in lenalidomide-refractory myeloma



– Daratumumab in combination with carfilzomib and dexamethasone (D-Kd) was a safe and effective regimen for patients with relapsed multiple myeloma, even in those with disease refractory to lenalidomide, in an open label, phase 1b study.

The regimen was well tolerated, with low rates of neutropenia both overall and in the lenalidomide-refractory subset of patients, according to this subgroup analysis of MMY1001.

The D-Kd regimen produced deep and durable responses, with an “encouraging” median progression-free survival of approximately 14 months for lenalidomide-refractory patients, according to investigator Ajai Chari, MD, of the Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, New York.

Patients with lenalidomide-refractory multiple myeloma have often been excluded from recent phase 3 studies in the relapsed/refractory setting, Dr. Chari noted in a presentation of the data at the 2018 annual meeting of the American Society of Clinical Oncology. “With the increasing adoption of lenalidomide maintenance, based on overall survival benefit, clearly there’s a need for more data on lenalidomide-refractory, relapsed refractory myeloma.”

The analysis by Dr. Chari and his colleagues was based on 85 previously treated, carfilzomib-naive patients, of whom 51 were lenalidomide refractory, in the MMY1001 study.

Patients received carfilzomib on days 1, 8, and 15 of 28-day cycles and dexamethasone 40 mg once weekly. They received daratumumab weekly for the first 2 cycles, every 2 weeks for the next 4 cycles, and every 4 weeks thereafter. Ten patients received a standard single first dose of daratumumab, while 75 received a split first dose.

Some grade 3/4 hematologic toxicities were observed, and the rate of grade 3/4 neutropenia was 21% overall. The most common nonhematologic toxicities reaching grade 3/4 included asthenia and hypertension at 12% and 14%, respectively. A similar safety profile was seen in the lenalidomide-refractory subset, according to Dr. Chari.

Grade 3 cardiac treatment-emergent adverse events were seen in seven patients, and resolved in five of them. One patient had a grade 4 event that resolved. Cardiac adverse events improved in grade upon interruption of carfilzomib, Dr. Chari said.

With a median follow-up of 12 months, the response rate was 84% overall, which was comparable to the 79% rate seen in the lenalidomide-refractory patients and 90% rate seen in the patients who were exposed to lenalidomide but not refractory, according to Dr. Chari.

Median progression-free survival had not been reached for the overall patient cohort but was 14.1 months in the lenalidomide-refractory cohort, Dr. Chari said. The 12-month rates of progression-free survival were 71% overall, 62% for lenalidomide-refractory patients, and 87% for lenalidomide-exposed patients.

Median overall survival was not reached overall, not reached in lenalidomide-exposed patients, and was 21.1 months in the lenalidomide-refractory group, he added.

Infusion-related reactions occurred in 5 out of 10 patients who received a standard single first infusion of daratumumab. In patients who received a split first infusion, reactions were seen in 27 (36%) on day 1 and in 3 (4%) on day 2. “Importantly, I think this study highlights the ability to do split dosing, particularly in community practices, and to improve patient convenience,” Dr. Chari said.

Dr. Chari reported disclosures related to Janssen Oncology, the maker of daratumumab, and Amgen, the maker of carfilzomib, as well as Acetylon Pharmaceuticals, Adaptive Biotechnologies, Array Biopharma, Bayer, Biotest, Bristol-Myers Squibb, Celgene, Millennium, Novartis, Onyx, Pharmacyclics, Seattle Genetics, and Takeda Pharmaceutical.

SOURCE: Chari A et al. ASCO 2018, Abstract 8002.

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