Watch KOL expert series
on continuous frontline treatment with DARZALEX® (daratumumab) + Rd and patient outcomes with Dr. Suzanne Reim Fanning, Associate Professor at USC School of Medicine Greenville.
View Transcript
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This is a nonaccredited promotional activity. This program was developed and approved by Janssen Biotech Incorporated.
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Faculty are compensated to present this information on behalf of the company and must do so in compliance with the US Food and Drug Administration regulations.
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INDICATIONS
DARZALEX® (daratumumab) is indicated for the treatment of adult patients with multiple myeloma:
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In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy.
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Select Important Safety Information.
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CONTRAINDICATIONS
DARZALEX® is contraindicated in patients with a history of severe hypersensitivity, for example, anaphylactic reactions, to daratumumab or any of the components of the formulation.
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Warnings and Precautions: Infusion-Related Reactions
DARZALEX® can cause severe and or serious infusion-related reactions including anaphylactic reactions. These reactions can be life-threatening, and fatal outcomes have been reported.
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Pre-medicate patients with antihistamines, antipyretics, and corticosteroids. Frequently monitor patients during the entire infusion. Interrupt DARZALEX® infusion for reactions of any severity and institute medical management as needed. Permanently discontinue DARZALEX® therapy if an anaphylactic reaction or life-threatening Grade 4 reaction occurs and institute appropriate emergency care. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion.
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Additional Important Safety Information will be reviewed later in this video.
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DR. SHAIN: I see a broad range of patients with newly diagnosed, transplant-ineligible multiple myeloma in my practice, and I usually spend time taking into account their individual characteristics.
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DR. SHAIN: The question I face is one that you may also encounter—whether the benefits and safety profile of a particular frontline therapy line up with the needs and the medical situation of the patient.
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DR. SHAIN: Hello, I am Dr. Kenneth Shain. Join me, as I discuss a frontline treatment option for newly diagnosed, transplant-ineligible multiple myeloma patients...
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DR. SHAIN:...based on evidence of efficacy and safety results from the MAIA study at 30 months, as well as the follow-up data at approximately 5 years.
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DR. SHAIN: Here is Janice, a patient I typically treat in my practice. She is a 73-year-old retired schoolteacher and a grandmother who was recently diagnosed with multiple myeloma and is not eligible for autologous stem cell transplant. She presented with International Staging System, or ISS, stage II as well as Eastern Cooperative Oncology Group, or ECOG, performance status of 1.
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When considering a frontline treatment option, we need to be thoughtful of her patient characteristics.
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DR. SHAIN: DARZALEX® plus lenalidomide and dexamethasone offers the opportunity for advancing frontline treatment with your patients who are newly diagnosed and transplant-ineligible.
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DR. SHAIN: The MAIA study was a large, randomized, open-label, multicenter, active-controlled phase 3 study of DRd, vs Rd alone.
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DR. SHAIN: The study included 737 adult patients with newly diagnosed multiple myeloma who were ineligible for autologous stem cell transplant.
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Patients were randomized, 1 to 1, to either receive DARZALEX® 16 mg/kg by intravenous infusion, weekly for Cycles 1 and 2, every 2 weeks for Cycles 3 through 6, and every 4 weeks for Cycles 7 and beyond, in combination with oral lenalidomide 25 mg daily on Days 1 through 21 and oral dexamethasone at 40 mg weekly in the DRd arm; or oral lenalidomide at 25 mg daily, Days 1 through 21, and oral dexamethasone 40 mg weekly, as the active control group: the Rd arm.
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Patients in both treatment arms continued until disease progression or unacceptable toxicity.
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DR. SHAIN: The primary endpoint of the study was progression-free survival.
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Key secondary endpoints included a percentage of patients with complete response rate, very good partial response rate, minimal residual disease-negativity rate, overall response rate, overall survival, and of course, safety.
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DR. SHAIN: Let’s first look at the demographics of the patients included in the study.
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The median age was 73 years, with a range of 45 to 90 years in the DRd arm, with 44% of the patients aged 75 years or more.
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In the DRd arm, thirty-four patients, or 35%, had an ECOG performance score of 0, 48% had an ECOG performance score of 1, and 17% had an ECOG performance score of 2 or more.
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Twenty-seven percent of patients had an ISS stage I, 44% had an ISS stage II, and 29% had an ISS stage III disease.
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DR. SHAIN: I am always inclined to look at the data when making a treatment decision for patients who have distinctive needs.
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So, for a patient like Janice let’s see how DRd fits into a frontline treatment.
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DR. SHAIN: The MAIA study reported that DRd demonstrated superior efficacy vs Rd alone.
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Let’s first discuss the primary analysis data and then we can get into the approximately 5-year follow-up results.
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As mentioned, progression-free survival was the primary endpoint for the MAIA study. Let’s take a look at the results of this key data point.
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DR. SHAIN: The median progression-free survival for DRd was not reached in the MAIA study, while the median progression-free survival for Rd was 31.9 months.
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The median follow-up was about 30 months. The data reported a hazard ratio of 0.56; with a 95% confidence interval of 0.43 to 0.73, and a p-value of <0.0001.
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This amounts to a 44% reduction in the risk of disease progression or death with DRd vs Rd alone.
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DR. SHAIN: At about 30 months, 70.6% of patients had not progressed with DRd vs 55.6% of patients in the Rd group.
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DR. SHAIN: Findings from the MAIA study also demonstrated the impact of the DRd combination regimen on the overall survival in the frontline setting, which was a secondary endpoint.
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DR. SHAIN: In the follow-up analysis at approximately 5 years, MAIA demonstrated an improvement in the overall survival in the DRd arm as compared to the Rd arm. The hazard ratio was 0.68, with a 95% confidence interval of 0.53 to 0.86, and a P-value of 0.0013, representing a 32% reduction in the risk of death in patients treated in the DRd arm. Additionally, median overall survival was not reached for either arm.
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Thus, the evidence presented so far supports choosing frontline DRd to give patients like Janice the opportunity to live longer than with Rd alone.
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DR. SHAIN: Now let’s look at the progression-free survival results for the follow-up analysis at approximately 5 years in the MAIA study.
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It’s important to note that this information is not included in the current Prescribing Information and has not been evaluated by the FDA.
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Additionally, this analysis was not adjusted for multiplicity and conclusions should not be drawn.
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DR. SHAIN: So how does progression-free survival for DRd fare vs Rd alone after about 5 years of follow-up? Median progression-free survival was not reached in the DARZALEX® plus Rd versus 34.4 months with the Rd alone. As you can see, more patients continued living without progression in frontline DRd, with the data showing 53% of patients were progression-free vs 29% for patients on the Rd alone. The hazard ratio was 0.53, with a 95% confidence interval of 0.43 to 0.66, representing a 47% reduction in the risk of disease progression or death with DRd vs Rd alone.
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DR. SHAIN: Now let’s take a moment to review the safety profile of DRd reported in the primary analysis as I know it is a key factor when selecting frontline treatment.
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In the primary analysis, safety and tolerability were evaluated at a median follow-up of about 30 months.
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The most frequent adverse reactions reported in 20% or more of patients in the DRd arm were diarrhea, constipation, nausea, vomiting, upper respiratory tract infection, bronchitis, pneumonia, infusion-related reactions, peripheral edema, fatigue, asthenia, pyrexia, back pain, muscle spasms, dyspnea, cough, peripheral sensory neuropathy, and decreased appetite.
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Serious adverse reactions with at least a 2% greater incidence in the DRd arm compared with the Rd arm were pneumonia, bronchitis, and dehydration.
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DR. SHAIN: The most frequent hematologic laboratory abnormalities were neutropenia, leukopenia, lymphopenia, thrombocytopenia, and anemia.
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Hematologic abnormalities were more prevalent in the DARZALEX® plus Rd arm compared to the Rd arm, except for anemia, which showed a lower incidence in the DARZALEX® plus Rd arm.
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DR. SHAIN: It’s also important to know that in the MAIA trial, infusion-related reactions of any grade with DARZALEX® plus Rd occurred in 41% of patients. Two percent were Grade 3 and less than 1% were Grade 4. Infusion-related reactions of any grade or severity may require management by interruption, modification and/or discontinuation of the infusion.
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DR. SHAIN: Furthermore, in more than 2000 patients assessed through clinical trials of DARZALEX® as monotherapy or combination therapy, the frequency of infusion-related reactions during Week 1 infusions was 37%....
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DR. SHAIN:...2% during Week 2 infusions...
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DR. SHAIN:...and 6% with subsequent infusions.
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DR. SHAIN: Like efficacy, the safety profile of DRd has been continuously evaluated in long-term follow-up analyses.
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It’s important to note that treatment-emergent adverse events are reported as observed. Additionally, these analyses are not included in the Prescribing Information and have not been adjusted for multiple comparisons. Therefore, no conclusions should be drawn.
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DR. SHAIN: The results show that the safety profile remained similar for DRd in patients over about 5 years of treatment, despite a median treatment duration that was more than twice as long in the DRd group than in the Rd group (47.5 months vs 22.6 months).
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The most common grade 3 or 4 treatment-emergent adverse events in more than 15% of patients in either group were neutropenia (54% in the daratumumab group vs 37% of patients in the control group), pneumonia (18% vs 9%), anemia (17% vs 22%), and lymphopenia (16% vs 11%), respectively.
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DR. SHAIN: Now, let’s look at the treatment guidelines. According to the NCCN Guidelines, daratumumab in combination with lenalidomide and dexamethasone, is a recommended Category 1 preferred therapeutic option for patients with newly diagnosed, transplant-ineligible multiple myeloma.