First CELMoD combination gains regulatory approval in multiple myeloma
Iberdomide, a cereblon E3 ligase modulatory drug (CELMoD), was granted accelerated approval by the US FDA, in combination with daratumumab and dexamethasone, for treating patients with relapsed/refractory multiple myeloma (RRMM) who had received prior treatment with a proteasome inhibitor and immunomodulatory agent. The approval was supported by the improvement in minimal residual disease (MRD)-negative complete response (CR) rates with the iberdomide combination, compared with daratumumab-dexamethasone — 41% vs 21% — in the phase 3 EXCALIBER-RRMM trial, making this the first RRMM therapy to be approved based on MRD-negative CR, a co-primary endpoint along with progression-free survival (PFS) in EXCALIBER-RRMM.

China’s NMPA grants first global approval for felzartamab in myeloma
The combination of felzartamab (previously, TJ202/MOR202), an anti-CD38 monoclonal antibody, along with lenalidomide and dexamethasone, was granted approval  by China’s National Medical Products Administration for treating patients with RRMM who received ≥1 prior therapy. The approval was based on findings from the randomized NCT03952091(TJ202001MMY301) phase 3 trial conducted in China.

Improved MRD outcomes seen with daratumumab-based quadruplet in CEPEHEUS
Higher MRD-negativity rates with daratumumab-lenalidomide-bortezomib-dexamethasone (Dara-VRd), compared with VRd, in transplant-ineligible/-deferred patients with newly diagnosed myeloma, were seen in the CEPHEUS trial, previously reported in Nature Medicine. Per an updated analysis in Blood Advances, Dara-VRd induced deeper, more durable, and overall, higher and more sustained MRD-negativity, compared with VRd, translating to an improved PFS in patients who achieved MRD negativity.

MRD positivity at 3 months may signal high risk of early cilta-cel failure
A retrospective analysis published in the American Journal of Hematology evaluated clinical factors associated with early progression or death (within 12 months) in patients with RRMM receiving standard-of-care ciltacabtagene autoleucel. Prior BCMA-directed therapy, presence of extramedullary disease, and a CAR-HEMATOTOX score ≥ 2 were pre-treatment factors that independently predicted early progression/death. Bone marrow MRD-positivity at 3 months also signaled high risk of early treatment failure in a small subset of patients.

TP53 mutations drive high-risk myeloma independent of del(17p)
Loss of TP53 function via TP53 mutations, with/without concomitant deletion of the short arm of chromosome 17, del(17p), define high-risk myeloma, per the IMS-IMWG Consensus Genomic Staging criteria. An integrated multi-omics–based mechanistic study reported in iScience showed thatTP53 mutations have a dominant negative effect, conferring adverse prognosis that is independent of del(17p) and worse than that of del(17p)-positive myeloma without TP53 mutations.

Study examines potential for omitting step-up dosing for bispecific antibody therapies
Current prescribing information for bispecific antibodies (bsAbs) approved for treating patients with RRMM require step-up dosing (SUD) at treatment initiation and after prolonged dose delays. Omission of repeat SUD was safe and feasible, according to an analysis of six patients who continued teclistamab or talquetamab with extended dosing intervals without repeating SUD. The findings were reported in Experimental Hematology & Oncology.