TOPLINE

Adding felzartamab, a novel anti-CD38 monoclonal antibody, to lenalidomide-dexamethasone significantly extended progression-free survival (PFS) compared with lenalidomide-dexamethasone alone in Chinese patients with relapsed or refractory multiple myeloma, a phase 3 trial found. However, the treatment was associated with substantially greater toxicity, including neutropenia, lymphopenia, and pneumonia. 

METHODOLOGY

• CD38 antibodies such as daratumumab and isatuximab are central to treating relapsed or refractory multiple myeloma, but their complement-dependent cytotoxicity is linked to infusion-related reactions and possibly to reduced efficacy, particularly in patients with 1q21+. Felzartamab has reduced complement-dependent cytotoxic activity.
• To evaluate the efficacy and safety of felzartamab in combination with lenalidomide-dexamethasone, researchers conducted a randomized phase 3 trial at 41 hospitals in China. The study included 295 adults aged 18 years or older with relapsed or refractory multiple myeloma who had received at least one previous line of systemic therapy and were not intolerant or refractory to lenalidomide.
• Patients were randomly assigned 2:1 to receive intravenous felzartamab plus lenalidomide-dexamethasone (n = 195) or lenalidomide-dexamethasone alone (n = 100). Felzartamab (16 mg/kg) was given on days 1 and 4 of week 1, weekly during weeks 2-12, every 2 weeks during weeks 13-24, and every 4 weeks thereafter. 
• The primary outcome was PFS; secondary outcomes included overall response rate, very good partial response or better, and median duration of response. The median follow-up duration was 34.5 months in the felzartamab plus lenalidomide-dexamethasone group and 28.7 months in the lenalidomide-dexamethasone group. The efficacy analysis included 289 patients who received at least one dose of study treatment (191 in the felzartamab group and 98 in the lenalidomide-dexamethasone group), and the safety analysis also included 289 patients (192 and 97, respectively).
• Among patients with available cytogenetic testing, 51% (72 of 142) in the felzartamab group and 56% (41 of 73) in the lenalidomide-dexamethasone group had high-risk abnormalities by mSMART 3.0 criteria. The chromosomal abnormality 1q21+ was found in 44% (63 of 142) of patients receiving felzartamab plus lenalidomide-dexamethasone and 47% (34 of 73) of those receiving lenalidomide-dexamethasone alone.

TAKEAWAY

• The median PFS was 18.9 months with felzartamab plus lenalidomide-dexamethasone vs 10.4 months with lenalidomide-dexamethasone; the three-drug regimen reduced the risk for progression or death by 38% (hazard ratio [HR], 0.62; P = .0035).
• The overall response rate was 64% in the felzartamab group vs 56% in the lenalidomide-dexamethasone group; very good partial response or better was achieved in 43% vs 31%, respectively. The median duration of response was also longer in the felzartamab group (26.6 vs 18.5 months; HR, 0.55; P = .0072).
• In an exploratory post hoc analysis of patients with 1q21+, the median PFS was numerically greater with felzartamab plus lenalidomide-dexamethasone (17.6 vs 11.3 months; HR, 0.68; P = .15), but the difference was not statistically significant.
• Adverse events of grade ≥ 3 were more frequent in the felzartamab group than in the lenalidomide-dexamethasone group, with the most common ones being neutropenia (55% vs 23%), followed by lymphopenia (41% vs 15%) and leukopenia (39% vs 11%); the most common serious adverse event was pneumonia (22% vs 10%). Treatment-related deaths occurred in 6% of patients in the felzartamab group and 2% in the lenalidomide-dexamethasone group. Infusion-related reactions occurred in 33% of patients receiving felzartamab; all were grade 1 or 2.

IN PRACTICE

"[T]his is the first phase 3 trial to evaluate felzartamab in this population,″ the authors wrote. "The findings support felzartamab plus lenalidomide-dexamethasone as an effective treatment option for Chinese patients with relapsed or refractory multiple myeloma," they added.

SOURCE

The study, led by Haiyan He, PhD, of the Myeloma & Lymphoma Center at Shanghai Changzheng Hospital in Shanghai, China, was published online in The Lancet Haematology.

LIMITATIONS

All participants in this study were Chinese, which limited the generalizability of the findings to other populations. The overall survival findings remained immature at the time of analysis, so it was uncertain whether the PFS benefit would translate into a survival advantage. Cytogenetic data were missing for some patients, which may have introduced bias in subgroup analyses.

DISCLOSURES

The study was funded by TJ Biopharma. Five authors reported being employees of TJ Biopharma, and the remaining authors reported no competing interests. Additional author disclosures are reported in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.