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Darzalex ®? (daratumumab) Combination Regimens Show Positive Results for Newly Diagnosed and Relapsed Patients with Multiple Myeloma

Updated Phase 3 ALCYONE results featured as oral presentation at ASH 2018 show improved progression-free survival in newly diagnosed patients


Data from Phase 2 LYRA and GRIFFIN studies support the safety and efficacy of daratumumab combination treatments in newly diagnosed and relapsed patients, including the feasibility of a split first dose


BEERSE, BELGIUM, December 1, 2018 – The Janssen Pharmaceutical Companies of Johnson & Johnson announced today long-term results from the Phase 3 ALCYONE study showing that the addition of Darzalex® (daratumumab) to bortezomib, melphalan and prednisone (VMP) continued to demonstrate significant improvement in progression-free survival (PFS) in patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplantation (ASCT).[1] These data (Abstract #156), as well as updates from the Phase 2 LYRA (Abstract #152) and GRIFFIN (Abstract #151) studies in patients with multiple myeloma, were featured during an oral abstract session at the 60th American Society of Hematology (ASH) Annual Meeting in San Diego, CA.


Long-term Phase 3 ALCYONE results for daratumumab frontline combination therapy1


At a median follow-up of 27.8 months, study results showed the addition of daratumumab to VMP reduced the risk of disease progression or death by 57 percent compared to VMP alone (Hazard Ratio [HR] = 0.43; 95 percent confidence interval [CI] 0.35-0.54, p<0.0001).1 Daratumumab-VMP resulted in a 24 month PFS rate of 63 percent compared to 36 percent with VMP alone.1 The median PFS for daratumumab-VMP has not yet been reached, whereas the control arm of VMP alone had a median PFS of 19.1 months.1 In addition, a significantly higher overall response rate (ORR) (91 percent vs. 74 percent, respectively) was observed with the daratumumab combination compared to VMP alone.1 Daratumumab-VMP resulted in deeper responses, significantly improving the rate of very good partial response (VGPR) or better (73 percent vs. 50 percent) and more than doubling the rate of stringent complete response (sCR) (22 percent vs. 8 percent) compared to VMP alone.1 Daratumumab-VMP induced a higher rate of sustained minimal residual disease (MRD) negativity compared to VMP alone (10 percent vs. 2 percent, respectively).1 The previously reported primary results of this study formed the basis of the European Commission approval of daratumumab in combination with VMP in patients with newly diagnosed multiple myeloma who are ineligible for ASCT.


“Longer-term data from the pivotal ALCYONE trial show that daratumumab combination therapy continued to show improvement in progression-free survival and response rates in newly diagnosed patients with multiple myeloma, including older patients who are less likely to respond to treatment,” said Meletios A. Dimopoulos, M.D., Professor and Chairman of the Department of Clinical Therapeutics at the National and Kapodistrian University of Athens School of Medicine, Athens, Greece, and principal investigator. “These promising results support the use of daratumumab earlier in the treatment paradigm when transplant ineligible patients are more likely to benefit from therapy, and that continued therapy with daratumumab confers benefit.” 


In the ALCYONE study, the most common Grade 3/4 treatment-emergent adverse events (TEAEs) during Cycle 10 and onward for daratumumab-VMP included anaemia (4 percent), neutropenia (2 percent) and bronchitis (1 percent).1 No new safety signals emerged, and Grade 3/4 infections continued to be manageable.1


Phase 2 LYRA and GRIFFIN data support efficacy and safety of daratumumab in newly diagnosed patients, including those who are eligible for high-dose therapy/ASCT, and in relapsed patients[2],[3]


Response rates from the Phase 2 LYRA study were presented for the investigational use of daratumumab plus cyclophosphamide, bortezomib, and dexamethasone (CyBorD) in patients with newly diagnosed and relapsed multiple myeloma.2 The ORR and VGPR or better rates in 86 newly diagnosed patients were 79 percent and 44 percent, respectively, after 4 Cycles and increased to 81 percent and 56 percent, respectively, at the end of induction (median 6 Cycles).2 In addition, the VGPR or better rate in 14 relapsed multiple myeloma patients was 57 percent after 4 Cycles and increased to 64 percent at the end of induction, and the ORR stayed consistent at 71 percent (median 7.5 Cycles).2 The 18-month PFS rate was 78 percent in non-transplant newly diagnosed patients and 53 percent in relapsed patients.2 Additionally, the study, which investigated splitting the first dose of daratumumab to shorten the infusion time on Cycle 1, Day 1 (C1D1), showed a safety profile consistent with previous studies.2 Infusion reactions (IRs) occurred in 49 percent of patients on C1D1 and four percent on Cycle 1, Day 2 (C1D2). Fifty-four percent of newly diagnosed patients experienced IRs, the most frequent being chills (14 percent), dyspnea, pruritus and nausea (8 percent each), and cough (7 percent). Fifty-seven percent of relapsed patients experienced IRs, the most frequent being cough (21 percent), hyperhidrosis, dyspnea, and chills (7 percent each). Only two patients experienced a Grade 3 IR, and there were no Grade 4 IRs. There were no daratumumab discontinuations due to IRs. Median infusion time was 4.5 hours for C1D1 and 3.8 hours for C1D2.2 Grade 3/4 TEAEs were reported for 56 percent of patients and the most common (≥10 percent) was neutropenia (13 percent).2


Data presented on the Phase 2 GRIFFIN study investigated daratumumab in combination with bortezomib, lenalidomide and dexamethasone (VRd) in a 16-patient safety cohort of newly diagnosed patients with multiple myeloma who were eligible for high-dose therapy and ASCT.3 Results showed that by the end of consolidation therapy following ASCT, all patients enrolled in the safety run-in obtained VGPR or better, and 63 percent achieved complete response (CR) or better, including 25 percent of patients who achieved sCR.3 Additionally, 94 percent of patients remained progression-free on study treatment at a median follow-up of 16.8 months.3 In addition, 8 of the 16 patients (50 percent) were MRD negative at a level of 10-5 by the end of consolidation.3 Fourteen patients (88 percent) experienced Grade 3/4 TEAEs with 10 (63 percent) related to treatment with daratumumab.3 The most common Grade 3/4 TEAEs (≥10 percent) included neutropenia, pneumonia, thrombocytopaenia, lymphopenia, febrile neutropenia, leukopenia, rash and hypophosphataemia.3 Thirteen patients (81 percent) experienced infections of any grade, including upper respiratory tract infection (six patients), pneumonia (four patients), bronchitis (two patients), and otitis and viral gastroenteritis (two patients each).3 No deaths due to serious adverse events were reported and no patient discontinued treatment due to an adverse event.3 These data suggest that daratumumab induction does not negatively impact stem cell mobilisation as all 16 patients underwent successful mobilisation with subsequent ASCT.3


“Daratumumab offers consistent clinical benefit across all lines of therapy in multiple myeloma and the positive data from the ALCYONE, LYRA and GRIFFIN studies build on the strong body of evidence supporting daratumumab-based regimens,” said Dr Catherine Taylor, Haematology Therapy Area Lead, Europe, Middle East and Africa (EMEA), Janssen-Cilag Limited. “These are important findings for patients which also provide additional insight into the most effective ways to manage care.”

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Last Updated: 04-Dec-2018