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Adding daratumumab to lenalidomide-dexamethasone significantly delays disease progression and increases the response rate in patients with transplant-ineligible newly diagnosed multiple myeloma

Interim results from the phase III MAIA trial, presented as a late breaking abstract during the 2018 annual meeting of the American Society of Hematology (ASH), show that adding daratumumab (DARA) to lenalidomide-dexamethasone (Rd) results in 44% reduced risk of disease progression or death, compared to Rd alone in patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM). At 30 months, the DARA-Rd regimen was associated with a progression free survival (PFS) rate of 71% as compared to 56% with Rd alone. In addition DARA-Rd also induced a higher objective response rate (ORR) than Rd alone (93% vs. 81%) and the obtained responses were also of better quality (complete response [CR] or better: 48% vs. 25%). In one quarter of patients DARA-Rd completely eradicated the disease (minimal residual disease [MRD] negativity), while this was only the case in 7% of Rd treated patients. Importantly, MAIA included a high proportion of patients aged 75 years or older (44%), making these findings even more encouraging.

An autologous stem cell transplantation (ASCT) is the standard treatment for fit patients with MM. However, a large proportion of patients is not able to undergo an ASCT due to advanced age or coexisting health conditions. Based on the results of the FIRST trial, demonstrating a superior PFS of continuous Rd over melphelan-prednisone-thalidomide (MPT), Rd has become one of the standard treatment options for transplant-ineligible NDMM patients. In the POLLUX study of DARA-Rd was compared to Rd in patients with relapsed/refractory MM, demonstrating a risk of disease progression or death of 63%. The phase 3 MAIA trial evaluated DARA-Rd vs. Rd in patients with transplant-ineligible NDMM

MAIA enrolled 737 patients with NDMM who were deemed ASCT-ineligible and randomised them to Rd alone (R: 25 mg PO daily on days 1-21 until progressive disease [PD]; d: 40 mgb PO or IV weekly until PD), or Rd plus DARA (16 mg/kg IV; cycles 1-2: QW, cycles 3-6: Q2W, cycles 7+: Q4W until PD). The primary endpoint of the study was PFS, with the ≥CR rate, the ≥ very good partial response rate (VGPR), the MRD-negativity rate, ORR, overall survival (OS) and safety as secondary objectives.

The median age of patients in the trial was 73 years, with 44% of patients being 75 years or older. Just over half of the patients were male, 84% had an ECOG performance status 0/1 and 14% had high-risk cytogenetics features. An interim analysis of the trial after a median follow-up period of 28 months showed that patients treated with DARA-Rd were 44% less likely to have died or experience disease progression, compared with patients who received Rd alone. The median PFS was 31.9 months for patients treated with Rd alone, and was not yet reached for those who received Rd plus DARA (HR[95%CI]: 0.56[0.43-0.73]; p< 0.0001). The CR rate, defined as the proportion of patients with no detectable disease in the blood or urine and less than 5% of cancerous cells remaining in the bone marrow, was 47.6% for patients treated with DARA-Rd, compared with 24.9% for those who received Rd alone. The proportion of patients who achieved a VGPR or better was also significantly higher among patients treated with DARA-Rd than with Rd alone (79.3%, vs. 53.1%; p< 0.001). In addition, there was a more than 3-fold improvement in the proportion of patients achieving MRD negativity for Rd plus DARA than with Rd alone (24.2% vs. 7.3%; p< 0.0001).

Overall, the safety profile of DARA-Rd was consistent with findings from the POLLUX and ALCYONE trials. Higher rates (5% or more difference) of grade 3/4 pneumonia (14% vs. 8%) and neutropenia (50% vs. 35%) were observed in the DARA-Rd arm than with Rd alone. The incidence of invasive secondary primary malignancies (SPM) was 3% for DARA-Rd and 4% for Rd. Treatment emergent adverse events leading to death occurred in 7% of DARA-Rd patients vs. 6% with Rd alone.

In conclusion, these results strongly support the addition of daratumumab to Rd as a new standard of care for patients with transplant-ineligible NDMM.


T. Facon, et al. Phase 3 Randomized Study of Daratumumab Plus Lenalidomide and Dexamethasone (D-Rd) Versus Lenalidomide and Dexamethasone (Rd) in Patients With Newly Diagnosed Multiple Myeloma (NDMM) Ineligible for Transplant (MAIA). Presented at ASH 2018; Abstract LBA-2.

Speaker Thierry Facon


Thierry Facon, MD, Claude Huriez Hospital, Lille, France


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