|The following article features coverage from the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. Click here to read more of Hematology Advisor‘s conference coverage.|
Previously, addition of daratumumab (DARA) to bortezomib, thalidomide, and dexamethasone (D-VTd) plus autologous stem cell transplant (ASCT) was approved for transplant-eligible (TE) patients with newly diagnosed multiple myeloma (NDMM) based on part 1 of CASSIOPEIA, a 2-part, randomized, open-label, phase 3 study (ClinicalTrials.gov Identifier: NCT02541383). Now, a prespecified interim analysis of CASSIOPEIA part 2 has demonstrated clinical benefit of DARA maintenance in these patients, with significantly longer progression-free survival (PFS) with DARA than with observation. The findings were presented during the ASCO21 Virtual Scientific Program.
Patients were randomized to receive 4 cycles of induction and 2 cycles of post-ASCT consolidation with D-VTd or VTd (part 1). Those who achieved at least PR (n=886) were rerandomized to receive DARA (16 mg/kg IV Q8W) for up to 2 years of maintenance therapy (n=442) or observation (n=444) until disease progression. The new analysis assessed the efficacy and safety of DARA maintenance versus observation in patients with at least a partial response (PR) in part 1, regardless of induction/consolidation treatment, after 281 PFS events.
The primary endpoint was PFS following the part-2 randomization. Key secondary endpoints were time to progression (TTP) and rates of complete response (CR), minimum residual disease (MRD) negativity by next-generation sequencing, and overall survival (OS). Patients were stratified according to induction regimen (D-VTd vs VTd) and depth of response (MRD status and post-consolidation response).
At median follow up of 35.4 months, patients receiving DARA had a significantly longer median PFS compared with those under observation (Not reached [NR] vs 46.7 mo; hazard ratio [HR], 0.53; 95% CI, 0.42-0.68; P <.0001). This benefit in PFS for patients treated with DARA was consistent across most subgroups. However, the investigators also observed a significant interaction with induction/consolidation treatment arm (P <.0001), with the PFS benefit observed only in patients treated with VTd (HR, 0.32; 95% CI, 0.23-0.46) and not in the D-VTd arm (1.02; 0.71-1.47).
Patients receiving DARA had a significantly longer median TTP than patients under observation (NR vs 46.7 months; HR, 0.49; 95% CI, 0.38-0.62; P <.0001), and significantly more patients achieved CR in the DARA arm than in the observation arm (72.9% vs 60.8%; OR, 2.17; 95% CI, 1.54-3.07; P <.0001). MRD negativity (10-5) in patients who achieved CR was more frequent in the DARA arm than the observation arm (58.6% vs 47.1%; OR, 1.80; 95% CI, 1.33-2.43; P =.0001). The median OS was not reached in either arm.
The most common grade 3/4 adverse events (AEs) were pneumonia (DARA vs observation, 2.5% vs 1.4%), lymphopenia (3.6% vs 1.8%), and hypertension (3.0% vs 1.6%). Serious AEs occurred in 22.7% of the DARA arm and 18.9% of the observation arm; the most common was pneumonia (2.5% vs 1.6%). Second primary malignancies occurred in 5.5% of the DARA arm and 2.7% of the observation arm. DARA was discontinued due to an AE by 13 patients (3.0%).
“CASSIOPEIA part 2 demonstrated a clinical benefit of DARA maintenance in TE NDMM pts, with significantly longer PFS for DARA vs [observation],” the authors concluded. “DARA significantly increased deeper response and MRD negativity rates vs [observation], and was well tolerated with no new safety signals.”
Disclosure: Authors declared affiliations with industry. Please refer to the original abstract for a full list of disclosures.
Read more of Hematology Advisor’s coverage of the 2021 ASCO Annual Meeting by visiting the conference page.
Moreau P, Sonneveld P, for the CASSIOPEIA Study Investigators. Daratumumab (DARA) maintenance or observation (OBS) after treatment with bortezomib, thalidomide and dexamethasone (VTd) with or without DARA and autologous stem cell transplant (ASCT) in patients (pts) with newly diagnosed multiple myeloma (NDMM): CASSIOPEIA. J Clin Oncol. 2021;39(suppl 15; abstr 8004). doi:10.1200/JCO.2021.39.15_suppl.8004