Ann Hematol: Safety and efficacy of daramalimumab in patients with relapsed or refractory multiple myeloma in China: a Phase 1 dose-escalation study

In the global Phase 1/2 GEN501 and Phase 2 SIRIUS studies, darralimumab monotherapy has shown good safety and efficacy
in patients with relapsed/refractory multiple myeloma (RRMM).
One study evaluated daralimumab monotherapy for specific treatment
in Chinese patients with RRMM.

This 3-part, open-label, Phase 1 dose-escalation study included patients
who had previously received 2 ≥ lines of therapy.
Part 3 includes patients
who received proteasome inhibitors (PI) and immunomodulatory drugs (IMiD) and experienced disease progression in the last regimen.
Patients received intravenous daralimumab 8 mg / kg or 16 mg / kg in part 1 and 16 mg / kg
in part 2 + 3.
The primary endpoint was dose-limiting toxicity (DLT; Part 1), pharmacokinetics (part 1+2), and adverse events (AE).

A total of 50 patients were enrolled
.
The first 3 patients in Part 1 received daramalimumab 8 mg/kg, and the remaining patients in Parts 1-3 received daramalimumab 16 mg/kg
.
In the daramalimumab 16 mg / kg group (n = 47), the median number of patients received prior therapy was 4 lines; 32% were refractory to PI and IMiD, and 79% refractory to their last previous treatment
.
No DLT
occurred.
Thirty-six (77%) patients reported adverse events
in grade 3/4 treatment.
Thirteen (28%) patients experienced infusion-related reactions
.

At a median follow-up of 18.
5 months, the overall response rate was 43%.

The median progression-free survival (PFS) and overall survival (OS) were 6.
7 months and not reached, respectively; The 12-month PFS and OS rates were 35% and 70%,
respectively.
The pharmacokinetic results (n=22) were consistent with
other studies.

At doses of 8 mg/kg and 16 mg/kg, darralimumab IV was well tolerated by Chinese patients who had undergone extensive pretreatment; No new security issues
were identified.
The pharmacokinetic profile of daralimumab, observed in Chinese patients, is consistent with
previous observations.
Daramalimumab monotherapy showed good efficacy, with an ORR of 42.
6%
in the 16 mg/kg group.
Overall, these data suggest good benefit/risk
for daramalimumab monotherapy in Chinese patients with RRMM who have failed ≥ previous 2-line therapy, and for Chinese patients with previous treatments including PI and IMiD who demonstrated disease progression on the last treatment.

Original source:

Jing, H.
, Yang, L.
, Qi, J.
et al.
Safety and efficacy of daratumumab in Chinese patients with relapsed or refractory multiple myeloma: a phase 1, dose-escalation study (MMY1003).
Ann Hematol(2022).
https://doi.
org/10.
1007/s00277-022-04951-3