Improving outcomes in AL amyloidosis
Transcript: Investigational treatments
Professor Giovanni Palladini
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Well the scenario changed dramatically in AL amyloidosis because now we have a licenced drug and we have to fill the gap in what is not covered by this new combination that is Dara-CyBorD. So we need treatments for stage 3b patients, and what is promising in that setting is becoming independent I think, from proteasome inhibitors and possibly high dose or intermediate dose dexamethasone index patients who are very, very frail. So, I think immunotherapy and possibly even single agent daratumumab is very promising in these patients with advanced disease. Daratumumab is also promising there because these patients need a very quick response and response to daratumumab is indeed very, very quick. And then we have the patients who do not attain a satisfactory response with Dara-CyBorD. In the past we were satisfied with a less deep response, but now we would like to have a complete response or at least the VGPR plus organ response in all our patients.
So even if Dara-CyBorD is very effective, some patients will not attain a response there. So what can we do for these patients? 50% of patients with AL amyloidosis carry the translocation 11;14, and these patients are probably very sensitive to Bcl-2 inhibitor. A couple of studies on venetoclax were presented in Heidelberg in September, and the results were indeed extremely promising, even in the relapse refractory setting. So I think we should work for granting access to Bcl-2 inhibitors in patients who failed to attain a satisfactory response to Dara-CyBorD. And also what is extremely promising is CAR T-cells. There have been two small, but very interesting studies on CAR T-cells. In AL amyloidosis five patients were reported recovered overall. These are already published studies, but what's interesting, despite the small number of patients is that these subjects were very frail, were very heavily pretreated, but all of them attained a complete response with organ response. So, you know, I think we should work to extend studies on CAR T-cells in these subjects.
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