Shaji K. Kumar, MD, Professor of Medicine at Mayo Clinic, discusses long-term efficacy and post-hoc subgroup analyses of MAIA, a phase 3 study evaluating the efficacy of daratumumab in combination with lenalidomide and dexamethasone (D-Rd) to that of lenalidomide and dexamethasone (Rd) in multiple myeloma patients. Outcome measures and data from post-hoc analyses were recently presented at the American Society of Hematology Meeting & Exposition (ASH 2022).
Multiple myeloma is a blood cancer associated with uncontrolled growth of plasma cells. While the disease is treatable, relapses are common and some patients are refractory to first line treatment.
As Dr. Kumar explains, MAIA is a randomized, open-label, phase 3 study that included 737 newly diagnosed patients with multiple myeloma ineligible for high-dose chemotherapy and autologous stem cell transplant (ASCT), aged 45-90 years (median age of 73). Patients were randomized to receive either D-Rd or Rd in 28-day cycles. In the D-Rd arm, patients received daratumumab 16 mg/kg IV weekly for cycles 1 – 2, every 2 weeks for cycles 3 – 6, and every 4 weeks for cycle 7 and beyond. Patients in the D-Rd and Rd treatment arms received 25 mg of lenalidomide on days 1 – 21 of each 28-day cycle, and dexamethasone at 40 mg once a week for each cycle. Patients in both treatment arms continued until disease progression or unacceptable toxicity.
The prespecified interim analysis for overall survival (OS) found that after a median follow-up of 56.2 months, a 32% reduction in the risk of death was observed in the D-Rd treatment arm vs. Rd arm. Median OS was not reached in either arm (P = .0013). Median progression-free survival (PFS) was not reached after nearly 5 years and the PFS benefit observed with D-Rd was maintained, with a 47% reduction in risk of disease progression or death (P < .0001).
At ASH 2022, four abstracts from MAIA were presented. The first abstract presented was an updated efficacy analysis from the MAIA study reporting data after 64.5 months of median follow-up on the primary study endpoint (PFS), and on secondary endpoints (MRD negativity, overall response rate [ORR] and OS). Results from this analysis demonstrate that after a median follow-up of 64.5 months, PFS was improved with D-Rd compared to Rd (median, 61.9 months vs 34.4 months; P <.0001). A 34% reduction in the risk of death was observed with D-Rd compared to Rd; median OS was not reached with D-Rd versus 65.5 months with Rd (P <.0003). The most common grade 3/4 treatment-emergent adverse events (TEAEs; D-Rd/Rd) were neutropenia (54.1%/37.0%), anemia (17.0%/21.6%), pneumonia (19.5%/10.7%), and lymphopenia (16.5%/11.2%); grade 3/4 infection rates were 42.6%/29.6%. The most common serious TEAE in both arms was pneumonia (18.7%/10.7%). 14.6% of patients in the D-Rd arm and 23.8% of patients in the Rd arm discontinued treatment due to TEAEs.
The second abstract presented at ASH 2022 reported on a post-hoc efficacy analysis of MAIA patients aged <75 years, <70 years, and ≥70 to <75 years. Findings from this analysis were consistent with previously reported data from the MAIA study on age and showed D-Rd improved OS, PFS, MRD-negativity, and ORR compared to Rd alone in all three age groups examined.
The third abstract presented at ASH 2022 reported on a post-hoc efficacy analysis of MAIA patients ≥75 years of age, with International Staging System (ISS) stage III disease, with high cytogenetic risk, with renal insufficiency, and with extramedullary plasmacytomas. Patients with high cytogenetic risk (defined as having one or more of the following abnormalities: t[4;14], t[14;16], or del17p) had a median PFS of 45.3 months following treatment with D-Rd vs. 29.6 months with Rd alone (D-Rd, n=48; Rd, n=44).
Finally, in the fourth abstract presented at ASH 2022, patient-reported outcomes (PRO) data such as HRQoL and physical functioning were analyzed among a subgroup of frail patients. Of the 737 patients randomized in the MAIA trial, 341 patients were classified as frail (D-Rd, n=172; Rd, n=169). At a median follow-up of 64.5 months, frail patients treated with D-Rd reported greater improvements from baseline compared to those treated with Rd based on EORTC QLQ-C30 Global Health Status (GHS) scores and physical functioning at several time points, with 39% of patients treated with D-Rd staying on treatment with PRO assessment at Cycle 48 vs 17% in the Rd group. Additionally, patients treated with D-Rd showed notably large reductions (≥20-point change) in pain symptoms over time, larger than that seen in pts treated with Rd.
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