Yes Bisantrene like all chemotherapeutic drugs causes myelosuppression at high doses and this limits the dose patients can be given at once. The other anthracyclines (like doxorubicin) also have a lifetime dosage limit because of the cardiotoxicity risk. This can result in patients that are still responding to doxorubicin not being able to be given anymore drug. Of course none of this applies to Pillar 1 where Bisantrene will be used at very low doses to target FTO. At the doses that will be used here there is no myelosuppression (we know this from the old Phase I dose escalation trials).
Pillar 3 is actually based around the response rate in AML patients, not safety. It has been observed in all the historical and modern AML trials that Bisantrene works in some (~40%) of patients that resistant to anthracyclines. Bisantrene really has three things going for it: 1) Targets FTO (Pillar 1); 2) Less damage to the heart (Pillar 2); 3) Works well in some anthracycline resistant cancers (Pillar 3).
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