ORLANDO, Fla. — The combination of daratumumab, lenalidomide and dexamethasone demonstrated a favorable benefit–risk profile and yielded durable responses among patients with relapsed and/or refractory multiple myeloma, according to study data presented at the ASH Annual Meeting and Exposition.
Daratumumab (Janssen and Genmab) — an anti-CD38 monoclonal antibody — has shown robust efficacy and favorable safety as a single agent, as well as in combination with lenalidomide (Revlimid, Celgene) and dexamethasone, in patients with relapsed or refractory multiple myeloma.
“Multiple myeloma is still a deadly disease, so we need new and better treatments,” Torben Plesner, MD, professor of hematology at Vejle Hospital in Denmark, told HemOnc Today. “Rituximab [Rituxan; Genentech, Biogen Idec] and other anti-B-cell antibodies have dramatically changed the outcomes for patients with non-Hodgkin’s lymphomas, so there is reason to believe that a monoclonal antibody reacting with myeloma cells could become a game changer.”
Plesner reported the updated safety and efficacy of combined daratumumab, lenalidomide and dexamethasone after longer than 12 months of exposure in patients with relapsed and/or refractory multiple myeloma.
The study design of the ongoing, open-label phase 1/2 study comprised a dose escalation study (daratumumab 2 mg/kg to 16 mg/kg, plus lenalidomide and dexamethasone) and a cohort expansion using the recommended phase 2 dose (16 mg/kg daratumumab, plus lenalidomide and dexamethasone).
In the second part of the study, the researchers assigned weekly daratumumab (16 mg/kg) during the first two 28-day cycles, then every other week during cycles 3 through 6. Daratumumab was then administered monthly until disease progression or unacceptable toxicity.
Oral lenalidomide (25 mg) was assigned on days 1 through 21 of each cycle, with weekly dexamethasone (40 mg).
Safety served as the primary endpoint.
The expansion cohort included 32 patients who had a median of two prior lines of treatment (range, 1-3). The median follow-up was 15.6 months. Eleven patients (34%) had prior lenalidomide therapy.
Thirty-one percent of patients discontinued treatment due to disease progression (n = 5), treatment-related adverse events (n = 3) or physician decision (n = 2).
The most common treatment-related adverse events included neutropenia (81%), muscle spasms (44%), cough (47%), diarrhea (34%), fatigue (31%) and hypertension (28%). One patient reported grade 1 febrile neutropenia.
Seventy-eight percent of patients reported grade 3 to grade 4 neutropenia.
Fifty-six percent of patients (n = 18) reported infusion-related reactions, which were generally mild to moderate and mostly occurred during the first treatment cycle. These included cough (25%), allergic rhinitis (9%), nausea (9%), vomiting (9%), dyspnea (6%), nasal congestion (6%) and hypertension (6%).
Grade 3 infusion-related reactions — laryngeal edema and hypertension — occurred in two patients.
All patients with infusion-related reactions recovered; one patient discontinued treatment following recovery.
The overall response rate was 81%, with six partial responses, eight stringent complete responses, three complete responses and nine very good partial responses.
The median time to first response was 1 month (95% CI, 0.9-1.9). The median time to best response was 5.1 months (95% CI, 1.9-5.6).
The median duration of response has not been reached, with 88% of responding patients having not progressed or relapsed at the time of reporting.
Eighty-one percent of responding patients (n = 21) experienced responses that deepened over time.
Median PFS has not been reached. At 18 months, the PFS rate was 72% and the median OS rate was 90%.
“Our next step is to continue the work that has been initiated by testing daratumumab in phase 3 trials for relapsed and refractory myeloma and as part of a first-line treatment for myeloma,” Plesner said. “It is my hope and expectation that the results of the trials will show significant benefit of adding daratumumab to our treatment programs in these settings.” – by Cameron Kelsall
Plesner T, et al. Abstract 507. Presented at: ASH Annual Meeting and Exposition; Dec. 5-8, 2015; Orlando, Fla.
For more information:
Torben Plesner, MD, can be reached at Kabbeltoft 25, 7100 Vejle, Denmark; email: email@example.com.
Disclosure: Plesner reports research funding from Celgene, Janssen, Novartis and Roche, as well as advisory board roles with Celgene, Genmab and Janssen. Please see the abstract for a list of all other researchers’ relevant financial disclosures.