A therapy mixture referred to as D-VRd confirmed enhancements in minimal-residual illness responses in sure sufferers with newly identified a number of myeloma.
In sufferers with transplant-ineligible or -deferred newly identified a number of myeloma, including Darzalex (daratumumab) to Velcade (bortezomib), Revlimid (lenalidomide) and dexamethasone (VRd) demonstrated improved minimal-residual illness (MRD) responses.
These findings had been primarily based on an evaluation of MRD outcomes from the section 3 CEPHEUS trial, introduced on the 2024 ASH Annual Assembly.
As well as, the mix led to improved progression-free survival (PFS), no matter MRD unfavourable or optimistic standing.
Glossary
Minimal-residual illness (MRD): microscopic traces of most cancers that stay within the physique after receiving therapy. MRD-negativity means there aren’t any detectable traces of most cancers within the physique.
Development-free survival (PFS): time sufferers dwell with out their most cancers worsening or spreading.
Full response (CR): sufferers absolutely responded to therapy, that means they now not present indicators or signs of most cancers.
Partial response (PR): sufferers reply to therapy however not utterly, that means their tumors shrunk after receiving therapy.
Finish level: the principle aim of a research measured on the finish to see if the therapy labored.
Subcutaneous: therapy given beneath the pores and skin.
ECOG efficiency standing: a measurement of how independently sufferers can full every day duties. A rating of 0 means sufferers can carry out duties absolutely independently and a rating of 4 means they can’t carry out duties independently.
“These knowledge assist the usage of [Darzalex] together with VRd as a standard customary of care in sufferers with newly identified a number of myeloma who’re transplant ineligible or when transplant is deferred,” Dr. Sonja Zweegman from the Division of Hematology at Amsterdam UMC, Vrije Universiteit Amsterdam, Most cancers Middle Amsterdam, Netherlands, mentioned throughout a presentation of the information.
After a median follow-up of 58.7 months, at a ten-5 sensitivity, the general MRD-negativity charge was 60.9% for sufferers handled with Darzalex plus VRd (197 sufferers) versus 39.4% for these given VRd alone (198 sufferers). At a ten-6 sensitivity, the general MRD-negativity charges had been 46.2% for sufferers within the daratumumab plus VRd group versus 27.3% for the VRd group.
“It may be appreciated … that including [Darzalex] to VRd led to a 50% enhance in MRD negativity,” Zweegman mentioned.
The 54-month PFS charges had been 68.1% and 49.5%, respectively, decreasing the danger for illness development or demise by 43%. Zweegman famous that the MRD negativity charges had been usually constant throughout prespecified subgroups.
When evaluating cumulative MRD unfavourable full response (CR) charges from the sensitivity stage 10-5, sufferers reached MRD negativity quicker, with larger charges in any respect time factors. “And the distinction of the MRD negativity charges between the [two treatment groups] is growing as much as three years,” Zweegman added.
This identical impact was seen on the sensitivity stage 10-6, which is much more associated to PFS, she famous. “And importantly… [Darzalex] virtually doubles the MRD unfavourable CR charges that sustained for greater than 12, 24 and 36 months.”
As sensitivity stage 10-6, MRD-negative sufferers skilled superior PFS, in contrast with MRD-positive sufferers in each therapy teams. Additional, the 54-month PFS charges for MRD-negative sufferers handled with Darzalex plus VRd or VRd alone had been 86.2% and 79.0%, respectively. In MRD-positive sufferers, these charges had been 51% and 36.5%.
“So [Darzalex] offers PFS profit whatever the MRD negativity CR standing,” Zweegman mentioned.
Further Examine Findings
The CR or higher charge was 81.2% within the Darzalex group versus 61.6% within the VRd group. Within the Darzalex plus VRd group, the stringent CR, CR, excellent partial response (PR), and PR charges had been 65.0%, 16.2%, 11.7% and 4.1%, respectively. Within the VRd group, these respective charges had been 44.4%, 17.2%, 25.3% and 6.1%.
Relating to security, grade 3 or 4 (extreme or life-threatening) treatment-emergent unintended effects occurred in 92.4% of sufferers within the Darzalex group versus 85.6% of sufferers within the VRd group. Remedy-emergent unintended effects led to discontinuation of all research medication in 7.6% and 15.9% of sufferers, respectively.
The commonest any-grade treatment-emergent unintended effects included blood and lymphatic problems (Darzalex group, 82.7%; VRd group, 64.6%), together with neutropenia (55.8%; 39.0%), thrombocytopenia (46.7%; 33.8%) and anemia (37.1%; 31.8%). Gastrointestinal problems occurred (79.7%; 81.5%), together with diarrhea (56.9%; 59%) and constipation (38.1%; 42.1%); normal problems and administration-site circumstances (80.7%; 75.4%), together with peripheral edema (42.1%; 39%) and fatigue (32%; 30.8%). Psychiatric problems occurred (46.2%; 49.2%), together with insomnia (32%; 32.3%); infections (91.9%; 85.6%), together with higher respiratory tract an infection (39.6%; 32.8%) and COVID-19 (38.1%; 24.6%); and second major malignancies (7.6%; 9.2%).
Extra About MRD-Negativity in A number of Myeloma
“Everyone knows that MRD negativity is related to longer survival, and it is a sturdy prognostic for scientific finish factors in a number of myeloma and a key aim of a number of myeloma remedy,” Zweegman defined. “And subsequently, MRD negativity was supported by the [FDA Oncologic Drugs Advisory Committee] as an early finish level for accelerated approval in a number of myeloma.”
The section 3 CEPHEUS trial was the primary section 3 research of Darzalex with MRD as a major finish level. Within the trial, investigators demonstrated that the addition of subcutaneous Darzalex with VRd in sufferers with transplant-ineligible or transplant-deferred newly identified a number of myeloma led to superior charges of general and sustained MRD negativity, in addition to extra CR, and it considerably improved PFS.
On the 2024 ASH Annual Assembly, Zweegman reported on an expanded evaluation of MRD outcomes from the CEPHEUS trial.
Within the trial, investigators randomly assigned sufferers evenly to obtain Darzalex at 1,800 milligrams (mg) as soon as per week, then as soon as each three weeks, plus 1.3 mg per sq. meter of Velcade; 25 mg of Revlimid and 20 mg of dexamethasone; or VRd alone on the identical dosing schedule. Beginning in cycle 9, sufferers within the experimental group obtained 1,800 mg of Darzalex as soon as each 4 weeks plus 25 mg of Revlimid and 40 mg of dexamethasone; sufferers within the management group obtained Rd on the identical dosing schedule.
The general MRD-negativity charge with a CR or higher served because the trial’s major finish level. Secondary finish factors included PFS; the proportion of sufferers with sustained MRD negativity with a CR or higher for at the very least 12 months; and CR or higher charge.
Sufferers had been required to have an ECOG efficiency standing (PS) of 0 to 2 and a frailty rating of 0 or 1.
Reference
“Part 3 Randomized Examine of Daratumumab (DARA) + Bortezomib, Lenalidomide and Dexamethasone (VRd) Versus Alone in Sufferers with Transplant-Ineligible Newly Recognized A number of Myeloma or for Whom Transplant Is Not Deliberate As Preliminary Remedy: Evaluation of Minimal Residual Illness within the Cepheus Trial” by Dr. Sonja Zweegman, et al. Offered at: 2024 ASH Annual Assembly; December 7-10, 2024; San Diego, California.
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