Felzartamab plus lenalidomide-dexamethasone versus lenalidomide-dexamethasone for relapsed or refractory multiple...

Complement-dependent cytotoxicity (CDC) of CD38 monoclonal antibodies has been associated with infusion-related reactions and might contribute to reduced clinical efficacy of CDC-reliant CD38 antibodies, particularly in patients with relapsed or refractory multiple myeloma with 1q21+. We aimed to evaluate felzartamab, a novel anti-CD38 monoclonal antibody that retains potent antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis while exhibiting markedly attenuated CDC activity in Chinese patients with relapsed or refractory multiple myeloma.

In this open-label, parallel-controlled, randomised, phase 3 trial conducted at 41 hospitals in China, 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 refractory to lenalidomide were enrolled. Patients were randomly assigned (2:1) through a central interactive web response system, stratified by International Staging System stage, number of previous lines of therapy, and previous lenalidomide exposure, to receive intravenous felzartamab (16 mg/kg on days 1 and 4 during week 1, weekly week 2-12, every 2 weeks week 13-24, and every 4 weeks thereafter) plus once daily lenalidomide (25 mg orally on days 1-21 of each 28-day cycle) and once weekly oral dexamethasone (40 mg for patients aged ≤75 years and 20 mg for those >75 years) or lenalidomide and dexamethasone alone. The primary endpoint was progression-free survival, defined as the time from randomisation to disease progression or death from any cause, whichever occurred first, assessed by an independent review committee in the full analysis set (all randomly assigned patients who received at least one dose of study treatment). Safety was assessed in all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov (NCT03952091) and is closed to enrolment.

Between March 27, 2019, and Oct 20, 2021, 390 patients were assessed for eligibility, 295 of whom were enrolled and randomly assigned to felzartamab plus lenalidomide-dexamethasone (n=195) or lenalidomide-dexamethasone (n=100). The full analysis set included 289 patients (191 in the felzartamab plus lenalidomide-dexamethasone group and 98 in the lenalidomide-dexamethasone group). 185 (64%) of 289 patients were male, 104 (36%) were female, and all were of Asian ethnicity. At a median follow-up of 34·5 months (IQR 16·8-40·2) in the felzartamab plus lenalidomide-dexamethasone group and 28·7 months (10·8-38·8) in the lenalidomide-dexamethasone group, median progression-free survival was 18·9 months (95% CI 13·6-24·0) with felzartamab plus lenalidomide-dexamethasone versus 10·4 months (5·8-13·9) with lenalidomide-dexamethasone (hazard ratio 0·62 [95% CI 0·45-0·86]; p=0·0035). The most common grade 3-4 adverse events were neutropenia (105 [55%] of 192 vs 22 [23%] of 97), lymphopenia (79 [41%] vs 15 [15%]), leukopenia (74 [39%] vs 11 [11%]), thrombocytopenia (49 [26%] vs 11 [11%]), pneumonia (44 [23%] vs 13 [13%]), anaemia (33 [17%] vs 19 [20%]), hypokalaemia (30 [16%] vs ten [10%]), and upper respiratory tract infection (15 [8%] vs two [2%]). The most common serious adverse event was pneumonia (42 [22%] vs ten [10%]). Treatment-related deaths occurred in 11 (6%) of 192 patients in the felzartamab plus lenalidomide-dexamethasone group (five of unknown cause [possibly related to treatment], two due to pneumonia, one due to febrile infection, one due to cardiac arrest, one due to cerebral infarction, and one due to pneumonitis) and two (2%) of 97 patients in the lenalidomide-dexamethasone group (one due to pneumonia and one due to a fall]).

Felzartamab plus lenalidomide-dexamethasone significantly prolonged progression-free survival compared with lenalidomide-dexamethasone alone, supporting felzartamab plus lenalidomide-dexamethasone as a potential new treatment option for Chinese patients with relapsed or refractory multiple myeloma.

TJ Biopharma.