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Isatuximab plus bortezomib, lenalidomide, and dexamethasone is feasible and effective for newly diagnosed multiple myeloma patients who are ineligible or have no intent for autologous stem cell transplantation.

Newly diagnosed multiple myeloma (NDMM) patients ineligible for autologous stem cell transplantation (ASCT) have lower survival rates. Bortezomib (trade name Velcade)+lenalidomide (trade name Revlimid)+dexamethasone (VRd) is a standard-of-care regimen for NDMM. Patients ineligible for ASCT may benefit from the addition of novel agents to treatment regimens. 

A Phase 1b study in the journal Leukemia evaluated the preliminary efficacy, safety, and pharmacokinetics of isatuximab, an anti-CD38 monoclonal antibody, combined with VRd (Isa-VRd) in NDMM patients ineligible or with no immediate intent for ASCT. The study found Isa-VRd to be effective and feasible in this patient population.

Study Population

This study included 73 patients with a median age of 71 years. All participants received four 6-week cycles of Isa-VRd during the induction phase, followed by 4-week maintenance cycles with Isa-Rd. 

High Overall Response Rate in Efficacy Population

Safety was analyzed for the all-treated population and efficacy endpoints were analyzed for the efficacy population.The overall response rate was 98.6% in the efficacy population (n=71). Of these, 56.3% of patients achieved a complete response or better rate. Similar overall response rates were observed in subgroups of patients with poor prognosis.

Moreover, 36 out of 71 (50.7%) patients reached minimal residual disease negativity. The median progression-free survival (PFS) and overall survival estimates for the entire cohort were not reached. The PFS probability for the entire cohort at 1 and 2 years was 91 and 83.1%, respectively.

High Incidence of Treatment-Emergent Adverse Events

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Any-grade treatment-emergent adverse events (TEAEs) were reported in 73/73 patients in the safety population, of which 79.5% were Grade ≥3. Fourteen out of 73 patients experienced TEAEs leading to permanent study treatment discontinuation during the 2-year follow-up. Seven (9.6%) of the TEAEs led to death.

The most common TEAEs were hematologic abnormalities, constipation, diarrhea, asthenia, peripheral sensory neuropathy, peripheral edema and infusion reactions.

Isatuximab Pharmacokinetic Parameters Unchanged by VRd

The pharmacokinetic parameters of isatuximab were within the range previously reported in the literature, suggesting that VRd does not change the pharmacokinetics of isatuximab. The pharmacokinetic parameters for bortezomib and lenalidomide were also comparable to those previously reported in the literature.


Ocio, E. M., Perrot, A., Bories, P., Miguel, J. F. S., Blau, I. W., Karlin, L., Martinez-Lopez, J., Wang, S., Bringhen, S., Marcatti, M., Mateos, M., Rodriguez-Otero, P., Oliva, S., Nogai, A., Roux, N. L., Dong, L., Macé, S., Gassiot, M., Fitzmaurice, T., . . . Moreau, P. (2023). Efficacy and safety of isatuximab plus bortezomib, lenalidomide, and dexamethasone in patients with newly diagnosed multiple myeloma ineligible/with no immediate intent for autologous stem cell transplantation. Leukemia, 37(7), 1521–1529 https://doi.org/10.1038/s41375-023-01936-7