Olverembatinib Study in Patients With Heavily Pretreated Chronic Myeloid Leukemia

EP: 1.Team Introductions: CML Experts From UT Southwestern vs. Mayo Clinic

EP: 2.Chronic-Phase CML: The OPTIC Study

EP: 3.Cross Q&A: Ponatinib Dosing in Relapsed/Refractory Chronic-Phase CML

EP: 4.Chronic Myeloid Leukemia: Retrospective Analysis of the PACE Study

EP: 5.Cross Q&A: Arterial Occlusive Events With Ponatinib in the PACE Trial

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EP: 6.Olverembatinib Study in Patients With Heavily Pretreated Chronic Myeloid Leukemia

EP: 7.Cross Q&A: Role of Olverembatinib in Heavily Pretreated CML

EP: 8.Chronic Myeloid Leukemia: Long-Term Follow-up of Low-Dose Dasatinib

EP: 9.Cross Q&A: Real-World Use of Low-Dose Dasatinib in CML

EP: 10.Mayo Clinic and UT Southwestern “Face Off” Over Multiple Myeloma and CML

Transcript:

Judy Schreiber, PhD, RN: Thank you very much. And then we’ll move on to the next talk.

Kebede Begna, MD: This is a paper presented by…[The University of Texas MD Anderson Cancer Center]group in those patients who have resistance to ponatinib and multiple other TKIs [tyrosine kinase inhibitors], including patients with refractory CML [chronic myeloid leukemia] and PH [Philadelphia chromosome]–positive ALL [acute lymphoblastic leukemia]. As I said, these are patients who are relapsed more than 2TKI, including T315I mutation. As you know, even though ponatinib is effective in T315I-mutated CML, [it is not effective] in everybody. Even the previous paper suggested that only 50% of patients who are or have T315I mutation achieve response or remission. So it includes 30 patients, a small number, 23 chronic phase IV accelerator phase, and 2 blastic… AML, and 1 ALL. The dose chosen was 30 [mg], 40 [mg] ­every other day in 20- day cycle. This was learned from another trial. … [So] how did they choose 30 mg, 40 mg, and 50 mg every other day? They have shown that it is safe. Only about 23% or a quarter of patients develop grade 3or 4thrombocytopenia, and nonhematological toxicities were very mild, and it’s tolerable. Only 20% of heavily treated patients were considered to have bafetinib-related [adverse ]effect.

The efficacy, as you see here, complete cytogenetic response, even in patients who have T315I mutation­–resistance to third-generation TKI showed significant response. More than 60% of both of cytogenetic and more than 50% major molecular remission [in patients]. Among patients who are treated with ponatinib resistance, 54% responded. Those who are resistant to asciminib, 4 out of 5, 80% responded. Yes, this is a very small number, but however this led to a nationwide initiation of [a] clinical trial, as I said, registered on nct.org. As I said, this medication is approved in China, and it’s manufactured in China. They have included a phase ½ clinical trial, all of them conducted in China, and they have found that the recommended phase 2 dose is 40 mg every other day. The primary outcome was major cytogenetic remission. Also both in the chronic and the 3 cumulative incidences of achieving major cytogenetic response was higher. This is [an] open-label, single-line treatment. Some of the common [adverse ]effects recorded were skin hyperpigmentation and severe thrombocytopenia and proteinuria. Based on this study, the MD Anderson group, as I said, did the first clinical trial and now it is nationwide. It is good for our patients. As you know, some of the patients may not tolerate and may not respond to ponatinib and asciminib. So this is one of the treatments which are available for our patients with CML.

Transcript edited for clarity.