Including Darzalex to Velcade, Revlimid and dexamethasone improved therapy response and decreased the quantity of residual most cancers cells in sufferers with newly recognized a number of myeloma ineligible for a stem cell transplant.
Amongst sufferers with newly recognized a number of myeloma who weren’t eligible for a stem cell transplant, Darzalex (daratumumab), when added to the usual therapy of Velcade (bortezomib), Revlimid (lenalidomide) and dexamethasone (VRd), improved therapy response and decreased the quantity of most cancers left within the physique, based on outcomes from the section 3 CEPHEUS trial offered on the 2024 ASH Annual Assembly.
As well as, the mix led to improved progression-free survival (PFS), no matter minimal residual illness (MRD) adverse or optimistic standing.
“These information assist using [Darzalex] together with VRD as a traditional commonplace of care in sufferers with newly recognized a number of myeloma who’re transplant ineligible or when transplant is deferred,” Dr. Sonja Zweegman, Division of Hematology, Amsterdam UMC, Vrije Universiteit Amsterdam, Most cancers Heart Amsterdam, Netherlands, stated throughout a presentation of the info.
After a median follow-up of 58.7 months, at a ten-5 sensitivity, the general MRD-negativity price 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 have been 46.2% for the Darzalex plus VRd arm versus 27.3% for the VRd arm.
“It may be appreciated … that including Darzalex to VRd led to a 50% enhance in MRD negativity,” Zweegman stated.
Glossary:
Full response: full disappearance of most cancers.
Minimal residual illness (MRD): small quantity of most cancers cells remaining after therapy.
MRD negativity: no detectable most cancers cells remaining after therapy.
Development-free survival (PFS): size of time a affected person lives with out illness worsening.
Subcutaneous: below the pores and skin.
Thrombocytopenia: low platelet depend, which may result in simple bleeding.
Neutropenia: low neutrophil depend, which may enhance the danger of an infection.
Peripheral edema: swelling within the arms or legs.
The 54-month PFS charges have been 68.1% and 49.5%, respectively, decreasing the danger for illness development or dying by 43%. Zweegman famous that the MRD negativity charges have been typically constant throughout prespecified subgroups.
When evaluating cumulative MRD adverse full response (CR) charges from the sensitivity degree 10-5, sufferers reached MRD negativity sooner, with larger charges in any respect time factors. “And that the distinction of the MRD negativity charges between the 2 teams are growing as much as three years,” Zweegman added.
This similar impact was seen on the sensitivity degree 10-6, which is much more associated to PFS, she famous. “And importantly … [Darzalex] nearly doubles the MRD adverse CR charges that sustained for greater than 12, 24 and 36 months.”
As sensitivity degree 10-6, MRD-negative sufferers skilled superior PFS, in contrast with MRD-positive sufferers in each therapy arms. Additional, the 54-month PFS charges for MRD-negative sufferers handled with Darzalex plus VRd or VRd alone have been 86.2% and 79%, respectively. In MRD-positive sufferers, these charges have been 51% and 36.5%.
“So [Darzalex] gives PFS profit whatever the MRD negativity CR standing,” Zweegman stated.
Extra Findings from CEPHEUS
The entire response (CR) or higher price was 81.2% within the Darzalex group versus 61.6% within the VRd group. Within the Darzalex plus VRd group, the stringent CR, CR, superb partial response (PR) and PR charges have been 65%, 16.2%, 11.7% and 4.1%, respectively. Within the VRd group, these respective charges have been 44.4%, 17.2%, 25.3% and 6.1%.
Concerning security, grade 3/4 (extreme/life-threatening) treatment-emergent AEs (TEAEs; unwanted side effects) occurred in 92.4% of sufferers within the Darzalex group versus 85.6% of sufferers within the VRd group. TEAEs led to discontinuation of all research medication in 7.6% and 15.9% of sufferers, respectively.
The most typical any-grade TEAEs included blood and lymphatic issues (Darzalex arm, 82.7%; VRd arm, 64.6%), together with neutropenia (55.8%; 39%), thrombocytopenia (46.7%; 33.8%) and anemia (37.1%; 31.8%); gastrointestinal issues (79.7%; 81.5%), together with diarrhea (56.9%; 59%) and constipation (38.1%; 42.1%); normal issues and administration-site circumstances (80.7%; 75.4%), together with peripheral edema (42.1%; 39%) and fatigue (32%; 30.8%); psychiatric issues (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 main malignancies (7.6%; 9.2%).
MRD Negativity as an Finish Level
“Everyone knows that MRD negativity is related to longer survival, and it is a robust prognostic for scientific finish factors in a number of myeloma and a key objective 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 main finish level. Within the trial, investigators demonstrated that the addition of subcutaneous Darzalex with VRd in sufferers with transplant-ineligible or transplant-deferred newly recognized 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 evenly assigned sufferers to obtain Darzalex at 1800 milligrams (mg) as soon as per week in cycles 1 and a pair of, then as soon as each three weeks in cycles 3 to eight, plus 1.3 mg per sq. meter (mg/m2) of Velcade on days 1, 4, 8 and 11 of every 21-day cycle; 25 mg of Revlimid on days 1 to 14 of every cycle, and 20 mg of dexamethasone on days 1, 2, 4, 5, 8, 9, 11 and 12 of every cycle for eight cycles; or VRd alone on the similar dosing schedule. Beginning in cycle 9, sufferers within the experimental arm acquired 1800 mg of Darzalex as soon as each 4 weeks plus 25 mg of Revlimid on days 1 to 21 and 40 mg of dexamethasone on days 1, 8, 15, and 22 of every 28-day cycle; these within the management arm acquired Rd on the similar dosing schedule.
The general MRD-negativity price with a CR or higher served because the trial’s main 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 price.
References:
- “Part 3 Randomized Research of Daratumumab (DARA) + Bortezomib, Lenalidomide and Dexamethasone (VRd) Versus Alone in Sufferers with Transplant-Ineligible Newly Identified 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., Blood.
- “Daratumumab SC + bortezomib/lenalidomide/dexamethasone in sufferers with transplant-ineligible or transplant-deferred newly recognized a number of myeloma: outcomes of the section 3 CEPHEUS research” by Dr. Saad Usmani, Blood.
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