ASH 2024 | Using combination therapies with pomalidomide to overcome lenalidomide refractoriness in myeloma

Lenalidomide refractoriness is an important topic and recently the Greek Myeloma group have shown that it’s not only the refractoriness to lenalidomide but the time it is required to reach lenalidomide refractoriness is also a very important feature. So once we have a lenalidomide refractory situation, we need to use at least two different classes of agents. 

And here in the ASH Congress, we are presenting the DREAMM-8 data where belamaf is combined with pomalidomide to overcome LEN refractoriness. And the control arm is pom-vel-dex, so pomalidomide combined with bortezomib. So in this setting, the patients must not be refractory to bortezomib. So we are now defining patients for a subsequent line of therapy based on their prior exposure and prior refractoriness. So if a patient is PI sensitive and lenalidomide refractory, so the options are in the DREAMM-8 study, either combining with belamaf or with bortezomib. And certainly the outcome was better with the belamaf combination. And the pom-vel-dex combination was the standard of care in the CARTITUDE or the KARMMA studies, where they were compared with cellular immunotherapy. But if the patient is PI resistant and also exposed to anti-CD38 plus the lenalidomide refractoriness, then the options are less, and there are now current trials which are ongoing using bispecifics in combination with pom or with other agents to be able to overcome the refractoriness coming from the earlier lines.

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