Quadruplet Therapy Shows Promise in High-Risk Transplant-Eligible Myeloma Patients

Take-aways:

• The addition of daratumumab to carfilzomib, lenalidomide, and dexamethasone induces deep responses as an induction therapy in transplant-eligible, newly diagnosed patients with MM.
• The quadruplet treatment was combined with autologous HSCT.
• The ORR was 96%, including 92% at the level of VGPR, and the MRD negativity rate was 62%.

The addition of daratumumab to carfilzomib, lenalidomide, and dexamethasone (KRd) induced deep responses as an induction therapy in transplant-eligible patients with newly diagnosed multiple myeloma (MM) presenting with high-risk cytogenetic abnormalities, according to the phase II trial from the Intergroupe Francophone du Myelome (IFM 2018-04).

In previous research, KRd triplet combination plus transplantation demonstrated high efficacy with a favorable safety profile in patients with transplant-eligible, newly diagnosed MM.

The current phase II trial evaluated the quadruplet treatment approach in patients with a high-risk cytogenetic profile. The study enrolled 50 patients (median age, 57 years; range, 38-65 years) with previously untreated newly diagnosed MM and del(17p) (n=20; 40%), t(4;14) (n=26; 52%), or t(14;16) (n=10; 20%) mutations.

Patients received six cycles of induction with the quadruplet therapy, autologous hematopoietic stem cell transplantation (AHSCT), another four cycles of daratumumab KRd consolidation, a second ASCT, and finally daratumumab plus lenalidomide maintenance.

Two patients discontinued treatment due to severe adverse events (COVID-19 and drug-induced hepatitis, respectively), and two patients discontinued treatment due to disease progression, leaving 46 patients who completed quadruplet induction.

The overall response rate was 96%, including 92% at the level of very good partial response. Among the 37 evaluable patients post-induction, the minimal residual disease negativity rate was 62%.

The most common treatment-related grade 3/4 adverse events (>5% of patients) were neutropenia (38%), anemia (14%), thrombocytopenia (8%), infection (6%), renal insufficiency (6%), and deep vein thrombosis (6%).

“[Daratumumab plus] KRd as induction prior [to] AHSCT is safe and allows deep responses in transplant-eligible, newly diagnosed MM patients with high-risk cytogenetic profile,” the researchers concluded.

The IFM 2018-04 study is ongoing, and longer follow-up is still needed to evaluate the safety and efficacy of the overall strategy.

Reference

Touzeau C, Perrot A, Hulin C, et al. Daratumumab carfilzomib lenalidomide and dexamethasone as induction therapy in high-risk transplant eligible newly diagnosed myeloma patients: results of the phase 2 study IFM 2018-04. Abstract #S176. Presented at the 2022 European Hematology Association Congress, June 9-12, 2022.