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Addition of Daratumumab to a Treatment Plan for Transplant Ineligible Patients With Multiple Myeloma Proves Beneficial
It is estimated that there will be more than 34,000 multiple myeloma (MM) diagnoses in 2021, and roughly 12,000 individuals will die from the disease in the United States.1 Although in some cases patients with MM present no symptoms, most patients are diagnosed due to their symptoms which include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems, or infections.1
The standard treatment for patients with newly diagnosed MM who are not eligible for autologous stem-cell transplantation is lenalidomide plus dexamethasone. However, researchers wanted to better understand if the addition of Darzalex (daratumumab) would reduce the risk of disease progression or death among these patients.2
“The treatment of multiple myeloma becomes more complex with each relapse. Therefore, it is critical to achieve deep treatment responses and improved survival with frontline therapy,” said Thierry Facon, MD, professor of hematology at Lille University Hospital, Lille, France, in a press release.1
The Current Use of Daratumumab
Daratumumab is currently approved for 8 indications—3 of which are frontline, including newly diagnosed patients who are transplant eligible and ineligible.
According to Janssen, daratumumab has been used in more than 190,000 patients worldwide and more than 68,000 patients in the United States alone since its FDA approval in 2015. Additionally, daratumumab is the first CD38-directed antibody that has been approved to globally treat patients with multiple myeloma.1
In multiple phase 3 studies, including use in frontline and relapsed settings, the use of daratumumab has shown significant improvement in progression-free survival (PFS) and/or overall survival.1
A New Treatment Plan for Transplant Ineligible Patients With MM
The MAIA trial—a randomized, open-label, multicenter phase 3 study—observed 737 patients with newly diagnosed MM who were ineligible for autologous stem-cell transplantation.
The participants of the trial either received daratumumab plus lenalidomide and dexamethasone (daratumumab group) or lenalidomide and dexamethasone alone (control group). The study authors continued treatment among these cohorts until the occurrence of disease progression or unacceptable side effects were observed.
The endpoints and measures of the trial included3:
- progression free survival (PFS);
- percentage of patients with complete response or better;
- percentage of participants with very good partial response or better;
- percentage of participants with negative minimal residual disease;
- overall response rate;
- overall survival;
- time to disease progression;
- time to response;
- duration of response;
- time to subsequent anti-myeloma treatment;
- PFS on next line of therapy;
- change from baseline in European organization for research and treatment of cancer quality of life questionnaire;
- change from baseline in EuroQol-5 dimensions-5 levels (EQ-5d-5L) visual analogue scale to day 1 of cycle 3, 6, 9 and 12; and
- change from baseline in EQ-5D-5L utility score to day 1 of cycle 3, 6, 9 and 12.
According to the findings of the study, at 28 months—the trials median follow-up—disease progression or death had occurred in 240 patients (97 of 368 patients [26.4%] in the daratumumab group and 143 of 369 patients [38.8%] in the control group).2
“The estimated percentage of patients who were alive without disease progression at 30 months was 70.6% (95% confidence interval [CI], 65.0 to 75.4) in the daratumumab group and 55.6% (95% CI, 49.5 to 61.3) in the control group (hazard ratio for disease progression or death, 0.56; 95% CI, 0.43 to 0.73; P<.001),” the study authors explained.2 “The percentage of patients with a complete response or better was 47.6% in the daratumumab group and 24.9% in the control group (P<.001).”
Further study findings showed that a total of 24.2% of patients in the daratumumab group had results below the threshold for minimal residual disease (1 tumor cell per 105 white cells) (P<.001) compared with 7.3% of the participants in the control group.
The most commonly reported grade 3 or 4 adverse event during the trial included neutropenia (50.0% in the daratumumab group vs. 35.3% in the control group), anemia (11.8% vs 19.7%), lymphopenia (15.1% vs 10.7%), and pneumonia (13.7% vs 7.9%).
What Do These Results Mean for This Patient Population?
Based on the findings of the MAIA trial, the study authors concluded patients with newly diagnosed MM who were ineligible for autologous stem-cell transplantation experienced a significantly lower risk of disease progression or death when receiving daratumumab plus lenalidomide and dexamethasone, compared to those who received lenalidomide and dexamethasone alone.2
“These latest findings from the MAIA study demonstrate the impact of this [daratumumab] combination regimen on long-term survival in the frontline setting, further establishing the importance of [daratumumab] as a backbone therapy in the treatment of multiple myeloma,” said Craig Tendler, MD, vice president, late development and global medical affairs, oncology, Janssen Research & Development, LLC, in a press statement.1
“These results provide hope and confidence for newly diagnosed patients with MM seeking effective treatment regimens that improve long-term outcomes and reflect our commitment to continuing to explore the full potential of [daratumumab] in MM,” he continued.1
Dr Facon concluded, “[The MAIA] results strongly support the use of daratumumab, lenalidomide and dexamethasone as a new standard of care to extend survival and improve clinical outcomes in transplant ineligible patients with newly diagnosed MM.”
References:
- Johnson & Johnson. Janssen announces results from phase 3 MAIA study showing significant overall survival benefits for treatment with Darzalex® (daratumumab) in patients with newly diagnosed multiple myeloma who are transplant ineligible. Johnson & Johnson. June 12, 2021. Accessed October 20, 2021. https://www.jnj.com/janssen-announces-results-from-phase-3-maia-study-showing-significant-overall-survival-benefits-for-treatment-with-darzalex-daratumumab-in-patients-with-newly-diagnosed-multiple-myeloma-who-are-transplant-ineligible
- Facon T, Kumar S, Plesner T, et al. Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma. N Engl J Med. 2019;380(22):2104-2115. doi:10.1056/NEJMoa1817249
- Clinical Trials. Study comparing daratumumab, lenalidomide, and dexamethasone with lenalidomide and dexamethasone in participants with previously untreated multiple myeloma. ClinicalTrials.gov website. Accessed October 18, 2021. https://www.clinicaltrials.gov/ct2/show/NCT02252172
