Conference Will Highlight Strategic Treatment Delineation in AML, CML

Jorge E. Cortes, MD

As investigators have developed a greater understanding of treating hematologic malignancies, they have been faced with increasingly complex challenges, especially when classifying and treating these cancers. A lot has changed, according to Jorge E. Cortes, MD, director at the Georgia Cancer Center at Augusta University. Cortes shared his insights in an interview with Targeted Therapies in Oncology™ prior to the 26th Annual International Congress on Hematologic Malignancies®: Focus on Leukemias, Lymphomas, and Myeloma. The conference, hosted by Physicians’ Education Resource®, LLC (PER®), will be held in Miami Beach, Florida, in February 2022.

“There are many more challenges in classifying and understanding the biology,” said Cortes, who is a cochair of the conference. “There isn’t 1 type of AML [acute myeloid leukemia], there isn’t 1 type of CML [chronic myeloid leukemia], and there isn’t 1 type of myeloproliferative syndrome.”

Classifying and analyzing hematologic malignancies now involves morphology, cell surface markers, immunohistochemistry, and cytogenetic abnormalities. Further complicating the clinical picture is the identification of novel subclasses that have distinct molecular profiles and clinical behaviors, Cortes said.

Historically, AML was treated in the first-line setting using induction therapy with cytarabine and daunorubicin. Treating CML involved interferon, and myeloproliferative neoplasms were treated with hydroxyurea. Effective therapies were limited, and these were relatively simple to give.

Although now there are many more treatments available, that poses another challenge that involves treatment choice, treatment sequence, and timing of treatments. “How does the oncologist choose when there are 3 or 4 options for a given scenario?” Cortes asked. In addition, the speed at which the treatment landscape evolves is rapid and ever changing, making sharing of information more important than ever. These challenges and more will be addressed at the conference through case scenarios, question-and-answer sessions, and presentations by world-renowned experts.

The role of chimeric antigen receptor (CAR) T cells and other immune-based therapies will have expanded coverage during the conference. A full afternoon session will be dedicated to addressing advances in CAR T-cell therapy for hematologic malignancies and other immune-based therapies and strategies to overcome treatment resistance. Other sessions will focus on applying state-of- the-art treatment strategies in the clinical practice setting.

“Treatment with CAR T cells is a rapidly emerging field. They play a big role in pediatric acute lymphoblastic leukemia, but their role will expand beyond the pediatric setting,” Cortes said.

Molecular screening and information to help clinicians decide which screening panels to consider will be a topic of discussion, Cortes said.

“That’s a topic that inevitably comes up because there are so many approaches. They range from homegrown panels to commercial panels. These panels can offer identification of a few genes to some panels with hundreds of genes,” Cortes said. The clinician is challenged to make sense of this information and sometimes is given more information than what’s asked for. “How does the clinician know what’s valuable and what’s not? What’s valuable therapeutically? What’s valuable from a prognostic perspective? These are questions that will be addressed during the conference,” Cortes said.

Cortes anticipates that one area for important discussion will be research that evaluated venetoclax (Venclexta) in AML from the initial phase 1, phase 2, and randomized phase 3 studies, which established the agent as the standard of care in a short amount of time.

The FDA approved the agent in October 2020 in combination with azacitidine, decitabine, or low-dose cytarabine (LDAC) for the treatment of newly diagnosed acute myeloid leukemia in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy.¹ Venetoclax was previously granted provisional approval under the FDA’s accelerated approval program in November 2018.

The approval is primarily based on the results of 2 phase 3 studies, VIALE-A (NCT02993523) and VIALE-C. (NCT03069352) Results of the VIALE-A study, which were published in the New England Journal of Medicine² in August 2020, showed venetoclax plus azacitidine significantly reduced the risk of death by 34% (overall survival; OS) compared with azacitidine alone (median OS, 14.7 months vs 9.6 months; HR, 0.66; 95% CI, 0.52-0.85; P < .001).

Patients treated with venetoclax plus azacitidine had significantly higher rates of complete remission (CR), 37% (95% CI, 31%- 43%) compared with 18% (95% CI, 12%-25%) in patients treated with azacitidine alone (P < .001). The venetoclax plus azacitidine combination also led to higher rates of CR and CR with partial hematologic recovery (CR + CRh), with the combination showing a CR + CRh of 65% compared with 23% with azacitidine alone (P < .001).

The most frequent serious adverse reactions (≥ 5%), reported in 83% of patients treated with venetoclax plus azacitidine, were low white blood cell count with fever (30%), pneumonia (22%), blood infection (excluding fungal; 19%), and bleeding (6%).

For the VIALE-C study,³ the approval was based on the rate and duration of CR. Twenty-seven percent (95% CI, 20%-35%) of patients treated with venetoclax plus low-dose cytarabine (LDAC) achieved a CR (median duration of CR [DOCR], 11.1 months) vs 7.4% (95% CI: 2.4%-16%) of patients treated with LDAC alone (median DOCR, 8.3 months).

The median OS for patients treated with venetoclax plus LDAC was 7.2 months vs 4.1 months (HR, 0.75; 95% CI, 0.52-1.07; P = .114) for patients treated with LDAC alone. These OS results were not statistically significant.

The most frequent serious adverse reactions (≥ 10%), reported in 65% of patients treated with venetoclax plus LDAC, were pneumonia (17%), low white blood cell count with fever (16%), and blood infection (excluding fungal; 12%).

Another topic of discussion will be trials that look at elective treatment discontinuation or trials that focus on the effects of limiting chemotherapy, especially in CML. Discussions about connecting patients with optimal therapy also will garner much interest. “These are some of the important findings from clinical research that have been presented over the past year,” Cortes said.

The 4-day conference will take place at the Eden Roc Miami Beach hotel in Florida.

_REFERENCES:

_{1. FDA grants regular approval to venetoclax in combination for untreated acute myeloid leukemia. News release. Accessed October 21, 2020. https://bit.ly/3ptyC0G}

_{2.DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N Engl J Med. 2020;383(7):617-629. doi:10.1056/NEJMoa2012971}

_{3. Wei AH, Montesinos P, Ivanov V, et al. Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial. Blood. 2020;135(24):2137-2145. doi:10.1182/blood.2020004856}