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In the of newly diagnosed multiple myeloma patients ineligible for transplant, daratumumab (Darzalex) plus lenalidomide (Revlimid)/dexamethasone (D-Rd) improved progression-free survival (PFS) compared with lenalidomide/dexamethasone (Rd) alone. At the recent American Society of Hematology (ASH) annual meeting, researchers of the trial for patients with impaired renal function.

In this exclusive 番茄社区 video, study author , chief of the Myeloma Service at Memorial Sloan Kettering Cancer Center in New York City, offers his takeaways from the study.

Following is a transcript of his remarks:

Hello, my name is Saad Usmani. I'm the chief of the myeloma service at the Memorial Sloan Kettering Cancer Center. And I'm going to talk about the abstract that I had presented at ASH titled "Efficacy of Daratumumab, Lenalidomide, and Dexamethasone in Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma and Impaired Renal Function from the phase III MAIA Study Based on Lenalidomide Starting Dose" on behalf of the MAIA investigators.

Just as a background, I'm sure all of you know about the MAIA study that led to the approval of daratumumab plus len-dex for transplant-ineligible, newly diagnosed multiple myeloma patients. The original study was back in 2019. And subsequently we had updated the data with a median follow-up of 56 months showing both PFS and overall survival [OS] benefit of daratumumab len-dex compared to len-dex.

However, about 20-50% of multiple myeloma patients do have baseline renal impairment, and we wanted to do a deeper dive into that data set to see impaired renal function overall. And whether based on the starting dose of len that was received impacts the efficacy of this therapy or not.

So in total 737 patients were randomized, and there were 368 patients that were assigned to the D-Rd arm compared to 369 patients to the Rd arm. There were 37% of the patients in the D-Rd arm and 43% who received a len starting dose of 25 milligram out of the renal-impaired patient subgroup. And then the rest of the patients received a len starting dose that was less than 25 milligrams. So this was based on the len-dosing schema.

And although the study protocol suggested a len starting dose of 10 milligrams for patients with a baseline creatinine clearance of less than 50 mg, this recommendation was not followed for all patients because of investigative decisions that were allowed per protocol.

So 40 patients with baseline creatinine clearance less than 50 did receive len at 25 milligrams, whereas another 42 received creatinine clearance, who received less than 25 milligram dosing with creatinine clearance between 50 and 59.

With that being said, looking at the data with the median follow-up of 56.2 months, there was clear PFS benefit as well as OS benefit in patients who had this renal impairment in favor of the daratumumab arm. So despite these dosing adjustments, patients did have that PFS and OS benefit. And when we looked at the number of deaths among patients with renal impairment, that number too was comparable across the different arms of the study.

So, if I were to summarize, I'd say that after this 5-year follow-up, PFS and OS benefit was seen on the MAIA trial and the D-Rd arm, regardless of renal impairment and len starting dose. However, those recommendations according to len prescribing information should be followed. And among patients with renal impairment, OS was prolonged the most for patients who got len starting dose of less than 25 milligrams, but less pronounced for those who got the full dose.

So the key takeaway is, many of these transplant-ineligible patients will not receive a second line of treatment because there is attrition with each line of treatment and patients pass away from the disease. And frontline news of D-Rd will prolong disease control in these older patients, especially those with renal impairment, regardless of the len starting dose.

Thank you for listening to me.

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