Bruce D. Cheson, MD


May 24, 2012

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Welcome to another edition of Medscape Hematology. I am Dr. Bruce Cheson, from Georgetown University Hospital, Lombardi Comprehensive Cancer Center. This is part 2 of an American Society of Clinical Oncology (ASCO®) 2012 preview. In part 1, I talked about lymphoma and myeloma, and now I will talk about the leukemias.

Some very interesting new drugs have the potential to have a major impact in the management of patients with select types of leukemia. For example, we have new drugs for acute lymphoblastic leukemia (ALL). One drug that will be presented is blinatumomab.[1] Blinatumomab is a bi-specific T-cell engager. In the abstract that will be presented, this drug (which binds to the malignant cell and attracts killer cells, so it is bi-specific) was used in patients with pre-B-ALL. Obviously I can't reveal all the data, because we want you to go to the meeting to hear it, but the response rate to this drug was 68%, and there was very little of what had been bothersome in the earlier lymphoma studies, which was severe neurologic toxicity. The median survival was approximately 7 months. Of interest, you can integrate this agent with other drugs.

Another interesting drug is inotuzumab. This is a drug-antibody conjugate. Anti-CD22 monoclonal antibody is linked to a calicheamicin, which is a poison. In this study,[2] you will see the data on patients with relapsed/refractory ALL. The response rate here was also respectable -- 50% -- with 10% complete remissions and a median survival of 7 months.

That is ALL. Things continue to be somewhat depressing in acute myeloid leukemia (AML). We present an abstract[3] about a combination of 5-azacitidine and gemtuzumab ozogamicin (the drug that has been pulled from the market). Patients were over the age of 60 years, with untreated, non-M3 AML: a poor group of patients. This was a Southwest Oncology Group (SWOG) study -- SWOG 50703. From this poor group of patients, this report is about the "good risk" and the "poor risk" patients. The "good risk" patients are those age 60-69, with a Zubrod performance status of 0-1. The patients initially received hydroxyurea to bring the blast count down and then received azacitidine and gemtuzumab. Their response rates were interesting: approximately 40% relapse-free survival of 8 months and overall survival of 11 months. How does this compare with what might be expected with chemotherapy? It's hard to say in the absence of a randomized trial. Whether one will ever be done, I am not sure.

There was a lot on chronic myelogenous leukemia (CML), where there is the shell game again between all of the kinases, imatinib, nilotinib, dasatinib, and so on. One abstract was on ponatinib.[4] This drug is interesting because it has activity against the T315I mutation. The abstract that was presented was in CML patients, as well as Philadelphia chromosome-positive ALL patients, who were intolerant to dasatinib and nilotinib or who had this mutation. The response rate was impressive, whether it was in patients with the chronic phase, accelerated phase, or blastic phase.

For chronic lymphocytic leukemia (CLL), we also have interesting drugs. In this case, the 2 abstracts of note involve ibrutinib (formerly known as PCI-32765, the Bruton tyrosine kinase inhibitor). John Byrd[5] will be presenting some very exciting data on the use of this drug in untreated patients with CLL, achieving a response rate of more than 70%, and many of these responses were quite durable. In the older patient population, this oral, relatively nontoxic drug seems like the way to go.

The final abstract[6] I am going to mention involves the same agent but in combination with the anti-CD20 ofatumumab in relapse-refractory CLL. In a small number of patients treated with this combination, the response rate was 100%, including a number of complete remissions. This drug really has some potential in CLL.

We have potentially exciting news in ALL. In CLL, we are seeing a bit more of the same, but we are fine-tuning the excellent responses we have achieved in CML. Once again, AML is being left behind. Since we have been doing this for many years, we really need something better than 7 plus 3, and I sure hope that next year at ASCO, or even this year at the American Society of Hematology meeting, someone comes up with a good drug to at least add to, if not replace, that old, tired combination.

Bruce Cheson signing off from Medscape Hematology, and I look forward to seeing you at the upcoming ASCO meeting. Goodbye.


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