Daratumumab combination therapy extends progression-free survival in previously treated patients with multiple myeloma

According to results Janssen-Cilag International NV announced today, daratumumab also significantly increased the overall response rate (ORR) [83 percent vs. 63 percent, p<0.0001].

The median PFS in the daratumumab arm has not been reached, compared with a median PFS of 7.16 months for patients who received bortezomib and dexamethasone alone.

These data will be presented in full today at 3:10 – 3:25 p.m. CDT during the "Plenary Session: Including the Science of Oncology Award and Lecture" at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago. They have also been selected for inclusion in the ASCO Press Programme. In addition, these results will also be featured in an encore, oral presentation at the 21st Annual Congress of the European Hematology Association (EHA) on Sunday 12 June at 12:00 – 12:15 p.m. CEST (Abstract #LB2236).

"We saw clinically meaningful improvements in progression-free survival and overall response rates with daratumumab when combined with standard of care," said Antonio Palumbo, M.D., Myeloma Unit Chief, Department of Oncology, Division of Haematology, University of Torino, Italy.

"These compelling Phase 3 results demonstrate that a regimen built on daratumumab deepens clinical responses and help to underscore its potential for multiple myeloma patients who have been previously treated."

In addition to meeting the primary endpoint of improved PFS at a median follow-up of 7.4 months and significantly increasing the ORR compared to bortezomib and dexamethasone alone, daratumumab doubled rates of complete response (CR) or better [19 percent vs. 9 percent, p=0.0012], including doubling rates of very good partial response (VGPR) [59 percent vs. 29 percent, p<0.0001]. The median PFS has not been reached, compared with a median PFS of 7.16 months for patients who received bortezomib and dexamethasone alone. The treatment benefit of the daratumumab combination regimen was maintained across clinically relevant subgroups.1

"At Janssen we are committed to redefining the impact cancer has on patients, through delivering innovative research and solutions. We’re therefore extremely encouraged by the remarkable interim results of this study. The findings provide an important insight into the effect daratumumab can have in combination with established regimens, and illustrate the promise of this immunotherapy in earlier lines of treatment," said Jane Griffiths, Company Group Chairman, Janssen Europe, Middle East and Africa.

"We’re dedicated to exploring the full treatment value of daratumumab for multiple myeloma patients and look forward to the difference we can make with data like these."

Overall, the safety of the daratumumab combination therapy was consistent with the known safety profile of daratumumab monotherapy (D) and bortezomib plus dexamethasone (Vd), respectively. The most common (>25 percent) adverse events (AEs) [DVd/Vd] were thrombocytopenia (59 percent/44 percent), peripheral sensory neuropathy (47 percent/38 percent), diarrhea (32 percent/22 percent) and anaemia (26 percent/31 percent). Most common grade 3 or 4 AEs (>10 percent) were thrombocytopenia (45 percent/33 percent), anaemia (14 percent/16 percent) and neutropenia (13 percent/4 percent). The rate of Grade 3/4 infections/infestations was 21 percent in the DVd group and 19 percent in the Vd group. The most common Grade 3/4 infections/infestations treatment-emergent AEs, or TEAEs (=5 percent) was pneumonia (8 percent/10 percent). The number of patients with Grade 3 or 4 bleeding events (3 patients in DVd group, 2 patients in Vd group) was low in both treatment groups. Few (7 percent/9 percent) patients discontinued therapy due to a TEAE.1

About the MMY3004 (CASTOR) Trial

The Phase 3, multinational, open-label, randomised, multicentre, active-controlled MMY3004 study has included 498 patients with multiple myeloma who received a median of two prior lines of therapy. Sixty-six percent of patients received prior treatment with bortezomib; 76 percent received prior treatment with an immunomodulatory agent; and 48 percent received prior treatment with a PI and immunomodulatory agent.

Thirty-three percent of patients were refractory to an immunomodulatory agent, and 32 percent were refractory to their last line of prior therapy. Patients were randomised to receive either daratumumab combined with subcutaneous bortezomib and dexamethasone (n=251) or bortezomib and dexamethasone alone (n=247). Participants were treated with daratumumab until disease progression, unacceptable toxicity, or if they had other reasons to discontinue the study.1

On March 30, 2016, the MMY3004 (CASTOR) trial was unblinded after meeting its primary endpoint of improved PFS in a pre-planned interim analysis (HR = 0.39, p<0.0001). Based on the recommendation of an Independent Data Monitoring Committee (IDMC), patients in the standard of care treatment arm were offered the option to receive daratumumab following confirmed disease progression.2

Janssen will initiate discussions with regulatory authorities about the potential for a regulatory submission for this indication based on the results of this study. A comprehensive clinical study report is being prepared for submission to global health authorities.