Clinical, Real-World Data Support Use of Daratumumab in Newly Diagnosed Multiple Myeloma


Data support daratumumab as part of a standard of care regimen in the frontline setting for patients with newly diagnosed multiple myeloma.

Analyses of data from first-line treatment with daratumumab (Darzalex; Janssen Pharmaceutical Companies)-based regimens demonstrated deep and durable responses in patients with newly diagnosed (ND) multiple myeloma (MM), according to a presentation at the American Society of Hematology (ASH) 2021 Annual Meeting. Additionally, investigators observed a potential survival benefit for daratumumab in combination with lenalidomide and dexamethasone (Rd).

Previously, in the primary analysis of the phase 2 GRIFFIN trial (NCT02874742) assessing daratumumab plus lenalidomide, bortezomib, and dexamethasone (D-RVd) in patients with autologous stem cell transplant (ASCT)-eligible NDMM (with a median follow-up of 13.5 months), D-RVd was found to improve the rate of stringent complete response (sCR) by the end of post-ASCT consolidation versus RVd (42.4% vs 32.0%, 1-sided P=0.068).

Following this primary analysis, a longer follow-up at a median of 27.4 months was conducted. This longer follow up data demonstrated patients experienced deepened responses that were improved from D-RVd versus RVd (sCR rate: 63.6% vs 47.4%, 2-sided P=0.0253), according to the investigators. Additionally, this improvement from D-RVd versus RVd was seen in the minimal residual disease (MRD)-negativity (10–5) rate (62.5% vs 27.2%, P<0.0001) as well.

After patients received maintenance therapy for 24 months, investigators found that adding daratumumab to RVd induction and consolidation in conjunction with ASCT, followed by daratumumab plus lenalidomide (D-R) maintenance, provided a continuation of deep and durable responses in patients with transplant-eligible NDMM, including sCR and MRD-negativity (10–5 and 10–6) rates. Additionally, no new safety concerns were observed with this longer follow-up period, supporting the use of D-RVd induction and consolidation and D-R maintenance in patients with transplant-eligible NDMM.

“Despite treatment advances, multiple myeloma remains a complex, currently incurable blood cancer. The latest clinical trial data and real-world evidence presented for daratumumab at ASH shines a light on the potential of daratumumab-based combinations and sequencing approaches in the first-line, to tackle this complexity and improve patient outcomes,” said Edmond Chan MBChB MD (Res), EMEA therapeutic area lead hematology at Janssen-Cilag Limited, in a press release.

In additional updated results from the GRIFFIN study at a median follow up of 38.6 months, investigators noted that the D-RVd regimen for patients with transplant-eligible NDMM showed improved outcomes with the addition of daratumumab to VRd when followed by D-R maintenance therapy.

The key findings from the updated results showed sCR favored D-VRd compared to VRd alone (66% versus 47.4%; p=0.0096), with MRD-negativity rates at a maximum of 10-5 remaining higher in patients treated with D-VRd versus VRd alone (64.4% versus 30.1%; p<0.0001). Additionally, the progression-free survival (PFS) rate at 36 months favored daratumumab-VRd versus VRd alone (88.9% versus 81.2%).

Although the study was not powered by PFS, the investigators did observe that by the median follow-up point of 38.6 months, median PFS had not been reached in either arm. However, the updated trial results with longer-term follow up did not provide any new safety concerns from the earlier trial data.

“These updated findings from the GRIFFIN study are promising when adding daratumumab to VRd in the treatment of newly diagnosed, transplant-eligible multiple myeloma,” said GRIFFIN study investigator Jacob Laubach, MD, MPP, clinical director of the Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, in a press release.

At ASH 2021, additional analyses of daratumumab-based regimens in the treatment of patients with transplant-ineligible NDMM were presented from the phase 3 MAIA study. With research showing that 50% of patients with transplant-ineligible NDMM will not receive a second line of therapy, investigators looked to provide potential clinical sequencing scenarios for this population that uses both attrition rates and real-world evidence from the Flatiron Health electronic health record-derived de-identified database.

Using these clinical sequencing scenarios, investigators assessed the use of daratumumab in combination with Rd against bortezomib administered in combination with Rd. Based on the results of this modelled analysis, the data indicated a potential survival benefit for patients who received daratumumab in first-line treatment versus later in their treatment process. The investigators also noted further research remains necessary to generate clinical data that can confirm these results.

In a second ASH 2021 presentation assessing first-line daratumumab-Rd, investigators analyzed real-world evidence to gain additional insight into clinical sequencing scenarios for NDMM. The scenarios used by the investigators were based on results from a retrospective, observational cohort study evaluating patients from the Flatiron database.

Based on their analysis of the real-world data, investigators found that the real-world patient population demonstrated similar results to that of the modelled analysis used in the MAIA study. Furthermore, an early trend of PFS was observed to be similar to that of the MAIA study as well.

In another presentation at ASH 2021, investigators detailed the results of a post-hoc analysis of the phase 3 MAIA study that focused specifically on patients with renal impairment. Based on the results, investigators observed that approximately 20% to 50% of patients with MM have a baseline renal impairment, which can impact both treatment choice and efficacy. However, the exploratory analyses presented at ASH 2021 were able to demonstrate PFS and overall survival benefits in patients with MM who were treated with daratumumab-Rd compared to Rd alone, whether or not lenalidomide was administered as the starting dose.

“The clinical data presented at ASH support daratumumab as a foundational therapy for patients with newly diagnosed multiple myeloma in transplant-ineligible populations,” said Imran Khan, MD, PhD, US vice president, medical affairs, hematology at Janssen Scientific Affairs, in a prepared statement. “Real-world evidence about efficacy, safety, and adherence is becoming increasingly important for clinicians in optimizing treatment approaches for patients with multiple myeloma. We will continue to advance research that can provide important insights about daratumumab as part of a standard of care regimen in the frontline setting.”


New Clinical and Real-World Data Support Use of DARZALEX®▼ (daratumumab) in Patients with Newly Diagnosed Multiple Myeloma. Beerse, Belgium: Janssen Pharmaceutical Companies; December 11, 2021. Accessed December 13, 2021.

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