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OncLive News Network On Location: ASH 2023: Drs Ponce and Hobbs

 News Network: On Location at the 2023 ASH Annual Meeting. Each day, we will broadcast a series of interviews with top thought leaders, to learn their thoughts and reactions to data presented across oncology during the conference.

We are reporting from the 2023 ASH Annual Meeting!

Get ready for highlights of some of the top news presented each day during the meeting—and soon we’ll speak with Drs Gabriela Hobbs and Doris Ponce to discuss some new data in myeloproliferative neoplasms and leukemia as well as graft-vs-host disease.

Welcome to OncLive News Network! I’m Caroline Seymour.

Up-front treatment with the combination of navitoclax and ruxolitinib (Jakafi) significantly reduced spleen volume by 35% or more at week 24 (SVR35W24) compared with ruxolitinib plus placebo for patients with myelofibrosis; however, a significant difference was not observed in total symptom score (TSS) version 4.0 between the arms, according to findings from the phase 3 TRANSFORM-1 study.

The all-oral combination of revumenib (SNDX-5613), decitabine/cedazuridine, and venetoclax (Venclexta) demonstrated a 100% objective response rate (ORR) as well as safety for patients with relapsed/refractory acute myeloid leukemia (AML) enrolled in the small phase 1/2 SAVE study.

Primary outcomes from the randomized, phase III REACH3 (NCT03112603) study were confirmed in the 3-year updated analysis, demonstrating sustained efficacy with ruxolitinib vs best available therapy in patients with chronic graft-vs-host-disease, though adverse effects were higher with the JAK inhibitor due to prolonged exposure to treatment.

Finally, in results from the phase 2 AGAVE-201 trial (NCT04710576), treatment with axatilimab produced robust antitumor activity and durable responses in all 3 dose cohorts evaluated in patients with refractory and heavily pretreated chronic GVHD, with the highest response rate and least toxicity observed at the 0.3 mg/kg every-2-week dose.

Please be sure to check out more of our coverage from the 2023 ASH Annual Meeting at OncLive.com.

That’s all for today. Tomorrow, we’ll sit down with Drs Hayder Saeed and C. Ola Landgren, who will share their perspectives on critical research in lymphoma and multiple myeloma.

Thank you for watching OncLive News Network: On Location, I’m Caroline Seymour.

Videos

OncLive® will be LIVE with OncLive® News Network: On Location at the 2023 ASH Annual Meeting. Each day, we will broadcast a series of interviews with top thought leaders, to learn their thoughts and reactions to data presented across oncology during the conference.

Making the Most of New Data in MPN, Leukemia, and GVHD From ASH 2023: Drs Ponce and Hobbs

Gabriela Hobbs, MD, clinical director of Leukemia Service and assistant in medicine at Massachusetts General Hospital, discusses the role of molecular testing to determine resistance in chronic myeloid leukemia (CML).

In CML, BCR-ABL1 kinase domain mutational testing is an important tool to guide treatment decisions, says Hobbs. However, because patients with CML rarely present with 

 mutations, ABL1 testing is not typically indicated up front. Instead, patients who do not meet their treatment milestones per National Comprehensive Cancer Network or European Leukemia Net guidelines should undergo testing to determine if they have acquired resistance, Hobbs explains. 

Although acquired resistance mutations are rare, their presence can inform treatment selection, Hobbs says. For example, patients with 

 mutations are not going to benefit from second-generation TKIs. Instead, these patients should receive ponatinib (Iclusig) and be considered for transplant, concludes Hobbs. 

Gabriela Hobbs, MD, discusses the role of molecular testing to determine resistance in chronic myeloid leukemia.  



Dr. Hobbs on the Role of Molecular Testing to Determine Resistance in CML 

Gabriela Hobbs, MD, clinical director of Leukemia Service and assistant in medicine at Massachusetts General Hospital, shares advice on how to choose the appropriate second-line treatment option for patients with chronic lymphocytic leukemia (CLL) who are resistant to TKIs.

If a patient with CLL proves to be resistant to a second-generation TKI, subsequent administration of imatinib (Gleevec) would not be recommended, according to Hobbs. Instead, a choice should be made among other second-generation agents. At this point in the treatment journey, is important to ensure that the patient is taking their medications as prescribed and that a BCR-ABL1 kinase mutational analysis is conducted, adds Hobbs; this will help to inform which TKI a patient should receive.

 indicated that some patients who prove to be resistant to a TKI are not often switched to the correct subsequent TKI based on their mutations, says Hobbs. For example, a patient with a 

 mutation should not be put on a second-generation drug; rather, that patient should be switched to ponatinib (Iclusig). Patients who are not switched to the correct TKI can have negative outcomes, Hobbs concludes.

Gabriela Hobbs, MD, shares advice on how to choose the appropriate second-line treatment option for patients with chronic lymphocytic leukemia who are resistant to TKIs.



Dr. Hobbs on Choosing Optimal Second-Line Treatment Option for TKI-Resistant CLL

Gaby Hobbs, MD, clinical director, Leukemia Service, assistant in medicine, Massachusetts General Hospital, discusses managing ponatinib (Iclusig)-associated toxicities in chronic myeloid leukemia (CML).

During the 2020 ASH Annual Meeting & Exposition, findings from the phase 2 PACE and OPTIC trials showed that ponatinib resulted in high response rates with good outcomes in patients with chronic-phase CML who have progressed on second-generation TKIs. 

Regarding safety, ponatinib has been associated with an increased risk of cardiovascular events. As such, trials are evaluating whether patients who achieve a remission with the 45 mg starting dose of ponatinib can be dose reduced to 15 mg or 30 mg and remain in remission, explains Hobbs. Dose reductions could lower the risk of cardiovascular events, Hobbs adds.

Ultimately, data have demonstrated that ponatinib has utility as a treatment for patients with CML, Hobbs says. However, like all TKIs, it is important to manage the risk of serious adverse effects, particularly cardiovascular events. For example, patients receiving ponatinib should receive concurrent aspirin, says Hobbs. Additionally, consulting the patient’s cardiologist, primary care physician, or a cardio-oncologist may lend additional insight into managing the risk of cardiovascular events, concludes Hobbs.

Gaby Hobbs, MD, discusses managing ponatinib-associated toxicities in chronic myeloid leukemia.  



Dr. Hobbs on Managing Ponatinib-Associated Toxicities in CML 

Gabriela S. Hobbs, MD, clinical director, Leukemia Service, assistant in medicine, Massachusetts General Hospital, discusses the treatment landscape of chronic myeloid leukemia (CML).

Data may now support the discontinuation of tyrosine kinase inhibitors (TKIs) in some patients with CML. This is due to the success of TKIs in the treatment of some patients with this disease. Since patients are experiencing such benefit, TKI therapy may be safely discontinued, a suggestion supported by the NCCN. The first TKI that was FDA approved for the treatment of patients with CML was imatinib (Gleevec) in 2001, but multiple others have entered the landscape since then.

Hobbs says that her main focus is figuring out which drug will be successful in controlling the patient’s disease, as well as providing the possibility of not having to take these medications for the rest of their lives. This reduces the burden of side effects on the patient. There are not enough data yet on long-term side effects of TKIs in CML to fully support discontinuation, though.

Gabriela S. Hobbs, MD, clinical director, Leukemia Service, assistant in medicine, Massachusetts General Hospital, discusses the treatment landscape of chronic myeloid leukemia.

Dr. Hobbs Discusses the Treatment Landscape of CML

Gabriela S. Hobbs, MD, clinical director, Leukemia Service, assistant in medicine, Massachusetts General Hospital, discusses the updated NCCN guidelines in chronic myeloid leukemia (CML).

One of the most exciting shifts in the CML landscape has been the revisions to the NCCN guidelines, says Hobbs. The NCCN guidelines are widely followed by physicians both in the United States and internationally to help treat and manage patients.

In light of recent data supporting the discontinuation of tyrosine kinase inhibitors (TKI), the NCCN guidelines as well as the European Leukemia Net Guidelines have recognized these data. It is now incorporated into the guidelines for treating physicians to reference.

The updated guidelines were based on a variety of clinical trials, explains Hobbs. Some of these trials include the STIM trials, the TWISTER trial, and the DADI trial. These trials, in conjunction with other trials, show that it is safe to discontinue TKIs if done properly, states Hobbs.

Gabriela S. Hobbs, MD

Articles

Making the Most of New Data in MPN, Leukemia, and GVHD From ASH 2023: Drs Ponce and Hobbs

Dr. Hobbs on the Role of Molecular Testing to Determine Resistance in CML

Dr. Hobbs on Choosing Optimal Second-Line Treatment Option for TKI-Resistant CLL

Dr. Hobbs on Managing Ponatinib-Associated Toxicities in CML

Dr. Hobbs Discusses the Treatment Landscape of CML

Dr. Hobbs on the Updated NCCN Guidelines in CML