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D-Rd improves PFS over Rd in newly diagnosed multiple myeloma

Roshini Claire Anthony
28 Dec 2018
Professor Thierry Facon

The addition of daratumumab to lenalidomide and dexamethasone improved progression-free survival (PFS) in patients newly diagnosed with multiple myeloma (MM) who were ineligible for a stem cell transplant, according to interim results of the phase III multinational MAIA* trial.

“D-Rd significantly reduced the risk of progression or death by 44 percent in patients with transplant ineligible newly diagnosed MM,” said study author Professor Thierry Facon from the Hôpital Claude Huriez in Lille, France.

Patients newly diagnosed with MM who were ineligible for transplant, and with ECOG status 0–2 and creatinine clearance 30 mL/min (n=737, median age 73 years [44 percent age 75 years], 52 percent male, 92 percent Caucasian) were randomized to receive intravenous daratumumab (16 mg/kg QW during cycles 1–2, Q2W during cycles 3–6, and Q4W from cycle 7 onwards until progression) plus oral lenalidomide (25 mg/day on days 1–21 for each 28-day cycle until progression) and oral or intravenous dexamethasone (40 mg/week [or 20 mg/week for participants >75 years/BMI <18.5 kg/m2] until progression; D-Rd, n=368) or lenalidomide and dexamethasone (Rd; same doses as D-Rd group; n=369).

Patients on D-Rd received treatment for a longer period than those on Rd (median, 25.3 vs 21.3 months). Discontinuation rate was lower among D-Rd than Rd recipients (32 percent vs 57 percent), with disease progression the primary reason for discontinuation (15 and 24 percent of D-Rd and Rd recipients, respectively).

Over a median follow-up period of 28 months, patients who received D-Rd demonstrated superior PFS compared with Rd recipients (median, not reached vs 31.9 months; 30-month PFS, 71 percent vs 56 percent, hazard ratio, 0.56, 95 percent confidence interval [CI], 0.43–0.73; p<0.0001). [ASH 2018, abstract LBA2]

The overall response rate was also higher among D-Rd compared with Rd recipients (93 percent vs 81 percent; p<0.0001), as were the rates of complete response or better (47.6 percent vs 24.9 percent, odds ratio [OR], 2.75, 95 percent CI, 2.01–3.76; p<0.0001) and very good partial response or better (79.3 percent vs 53.1 percent, OR, 3.4, 95 percent CI, 2.45–4.72; p<0.0001). Minimal residual disease negativity rate (10-5) was also three times higher in D-Rd vs Rd recipients (24.2 percent vs 7.3 percent; p<0.0001).

Although still immature, data show a trend towards improved overall survival among D-Rd compared with Rd recipients (event rate, 17 percent vs 21 percent, HR, 0.78, 95 percent CI, 0.56–1.1).

The most common grade 3–4 treatment-emergent haematologic toxicity experienced by D-Rd and Rd recipients was neutropenia (50 percent vs 35 percent), with 12 and 20 percent, respectively, experiencing anaemia, 7 and 9 percent thrombocytopenia, and 15 and 11 percent lymphopenia, while the most common grade 3–4 non-haematologic toxicity was pneumonia (14 percent vs 8 percent). Treatment-emergent adverse events leading to death occurred in 7 and 6 percent of D-Rd and Rd recipients, respectively.

“We see a very strong clinically significant benefit in extending survival without the cancer getting worse, with no major safety concerns. In older patients who are not candidates for stem cell transplantation, these are very encouraging results,” said Facon.

“These results support D-Rd as a new standard of care for patients with transplant ineligible newly diagnosed MM,” he said.

“Overall, the trial tells us that the three-drug combination of daratumumab, lenalidomide, and dexamethasone is effective, well tolerated, and appears to be more effective than lenalidomide and dexamethasone,” added study co-author Professor Shaji Kumar from the Mayo Clinic, Rochester, Minnesota, US. However, the comparative efficacy of this combination vs other three-drug combinations (lenalidomide and dexamethasone in combination with bortezomib or carfilzomib) remains to be seen, he added.

 

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Most Read Articles
2 days ago
New drug applications approved by US FDA as of 01 - 15 June 2019 which includes New Molecular Entities (NMEs) and new biologics. It does not include Tentative Approvals. Supplemental approvals may have occurred since the original approval date. 
Audrey Abella, 3 days ago
The taxane-based TPEx regimen demonstrated encouraging overall survival (OS) benefit for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) compared with the fluorouracil (5FU)-based EXTREME regimen, according to the results of the TPExtreme* trial presented at ASCO 2019.