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COMy 2021 | ANCHOR & LIGHTHOUSE: melflufen-based combinations in R/R myeloma

Enrique M. Ocio, MD, PhD, Marqués de Valdecilla University Hospital, Santander, Spain, discusses current investigations into melphalan flufenamide (melflufen)-based combination therapies for patients with multiple myeloma. The Phase I/IIa ANCHOR trial (NCT03481556) of meflufen plus dexamethasone with bortezomib or daratumumab in patients with relapsed/refractory (R/R) myeloma is the first study assessing melflufen in combination with other agents. Follow-up is ongoing but early results in the melflufen-dexamethasone-daratumumab arm have shown promising response rates, with a good tolerability profile. A subsequent Phase III randomized trial (LIGHTHOUSE; NCT04649060) comparing melflufen plus daratumumab with daratumumab alone is currently enrolling. This interview took place during the 7th World Congress on Controversies in Multiple Myeloma (COMy), 2021.

Transcript (edited for clarity)

The ANCHOR trial, is a combination of melflufen in combination with either bortezomib or daratumumab. We know that melflufen is a novel concept. It’s a PDC, a peptide-drug conjugate, that binds an alkylator payload, which is melphalan to a radical that makes it inactive and very lipophilic. So going very quickly inside the tumor cells, inside the cells, and then it is released in the inside...

The ANCHOR trial, is a combination of melflufen in combination with either bortezomib or daratumumab. We know that melflufen is a novel concept. It’s a PDC, a peptide-drug conjugate, that binds an alkylator payload, which is melphalan to a radical that makes it inactive and very lipophilic. So going very quickly inside the tumor cells, inside the cells, and then it is released in the inside. The melphalan is released inside the cells. Particularly in the tumor cells because they are enriched in aminopeptidases. This ANCHOR trial is the first study evaluating the combination of melflufen with other agents. As I said, in this case, with bortezomib or with daratumumab. The most consolidated data is the one with daratumumab in which more than 30 patients, 33 patients, have been evaluated here, and we have a good response rate with 73% response rate.

The duration of the response on the progression-free survival is still early, but it’s more than one year, but I think it’s interesting. We need more follow-up I think but it’s very interesting. And I want to speak in favor of the tolerability of the combination. Patients are really clinically very well with this combination. We have the concern that the thrombocytopenia, but I think it’s also well managed with dose reductions. So this is the first combination to be tested with melflufen. Here we have selected 30 milligrams as the appropriate dose for the subsequent Phase III trial, which is the LIGHTHOUSE trial, which is just starting with daratumumab-dexamethasone plus/minus melflufen for these relapsed/refractory myeloma patients that I think will be a good and a promising strategy for multiple myeloma patients.

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Disclosures

Honoraria or consultancy fees from Janssen, BMS, Sanofi, GSK, Oncopeptides, Amgen, Takeda, Secura-Bio, MSD and Mundipharma-EDO