ASCO 2023: Experts Recount the Biggest Surprises and Most Relevant Research

After the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, CancerNetwork hosted a game show–style production called 2-Minute Drill, in which key experts in the hematologic oncology space faced rapid-fire questions about the meeting from a live, in-studio moderator. The program gauged their perspective on some of the most important developments and research.

The panel of experts discussing updates from 2023 ASCO.

The experts were Ruemu E. Birhiray, MD, a physician at Hematology Oncology of Indiana in Indianapolis; Sameer A. Parikh, MBBS, a hematologist and oncologist at Mayo Clinic in Rochester, Minnesota; Javier Pinilla, MD, PhD, senior member and head of the Lymphoma Section in the Department of Malignant Hematology at MoffittCancer Center in Tampa, Florida; and Nakhle Saba, MD, an associate professor of clinical medicine at the Tulane University School of Medicine in New Orleans, Louisiana.

The experts agreed that many important research advances emerged at this year’s annual meeting.

What trial do you think will be the most practice changing?

Dr Parikh on the phase 1/2 TRANSCEND CLL 004 trial (NCT03331198)¹

"In chronic lymphocytic leukemia [CLL], the trial I liked most was presented by Tanya Siddiqi, MD, and it was to do with a chimeric antigen receptor [CAR] T-cell therapy. In this study, patients with highly relapsed/refractory CLL—patients who had relapsed on both a previous Bruton tyrosine kinase [BTK] inhibitor as well as a venetoclax [Venclexta]– based regimen—were allowed to participate. These patients all received lisocabtagene maraleucel [Breyanzi], which is a CD19-directed CAR T-cell therapy. The remarkable finding here was that most of these patients had a terrific response to treatment. Not only did they respond, but the longevity or the duration of response was also quite remarkable. There were patients who experienced toxicity as we’ve all come to expect with CAR T-cell therapy, including cytokine release syndrome and neurotoxicity. However, these were relatively mild and easily treated. In my mind, this represents an important update out of all the CAR T-cell therapy trials we’ve seen thus far in relapsed/refractory CLL. Hopefully this will lead to the approval of CAR T [-cell regimens] in this setting, which will be huge because our patients with double-refractory CLL have no treatment options available right now. We have a long way to go.”

What was the biggest surprise that came out of the 2023 ASCO Annual Meeting?

Saba on the phase 3 LyMa trial (NCT00921414)²

"Being focused on lymphoma in my clinic, I would say the LyMa trial update [was most surprising]. I was surprised to see that the overall survival [OS] benefit was lost over time. In this trial, about 240 patients with mantle cell lymphoma were randomly assigned 1:1 to receive maintenance rituximab [Rituxan] for 3 years or to the observation after autologous stem cell transplantation arm. At the 2023 ASCO Annual Meeting, the 7-year update showed that the OS difference—about 83% vs 72%—lost statistical significance compared with [the data from] the 4-year mark. These are still great data that are very clinically meaningful.”

What trial will lead to the next FDA approval?

Birhiray on the phase 3 NATALEE trial (NCT03701334)³

"I suspect the trial that will lead to the earliest approval is going to be the ribociclib [Kisqali] trial in the treatment of breast cancer. That’s a trial in which a CDK4/6 inhibitor [was] added to [treatment for] stage II/III breast cancer and resulted in about a 30% improvement in disease-free survival and about a 25% improvement in invasive disease–free survival. There was a small trend toward a survival benefit. The study is still small, [and] it does have some weaknesses, though. One was that the study required [patients to have had] 3 years of prior BTK inhibitor [treatment] instead of 2 years. Another potential weakness is the fact that the study did not include minority patients. I was told [there were] about 100 minority patients in a 5000-patient study.”

What trial requires the most follow-up?

Pinilla on the phase 3 Alliance A041702 trial (NCT03737981)⁴

"The Alliance trial still needs to be followed. We’ve discussed how the triplet [regimens] are not showing any benefit over the doublet [therapies], but I don’t think [the doublet administered in this trial] was the right doublet to use. That said, it was an interesting early readout. We discussed the obvious toxicities there, [including] infection. Those patients are not a very good fit for too many drug combinations. In my opinion, from what I see in my practice, I would like to see longer follow-up from this trial.”

WINNERS

The final scores from the event.

Ruemu E. Birhiray, MD

“One cannot forget [the importance of] solid tumors, and [there’s been] a lot of activity in breast cancer. The ribociclib data [are promising]. Also, regarding brain tumors, the IDH-inhibiting drug [vorasidenib; AG-881] produced a significant improvement in outcomes for patients.5 There are a lot of opportunities [emerging].”

Nakhle Saba, MD

“These are very exciting times, indeed, in terms of cancer drug discovery, particularly in lymphoma. Now we just [need to] discover that ‘magic recipe’ from all these great ingredients to achieve more curative therapies.”

References

1. Sarkozy C, Thieblemont C, Oberic L, et al. Very long-term follow-up of rituximab maintenance in young patients with mantle cell lymphoma included in the LyMa trial, a LYSA study. J Clin Oncol. 2023;41(suppl 16):7508. doi:10.1200/JCO.2023.41.16_suppl.7508
2. Siddiqi T, Maloney DG, Kenderian S, et al. Lisocabtagene maraleucel (liso-cel) in R/R chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): primary analysis of TRANSCEND CLL 004. J Clin Oncol. 2023;41(suppl 16):7501. doi:10.1200/JCO.2023.41.16_suppl.7501
3. Slamon DJ, Stroyakovskiy D, Yardley DA, et al. Ribociclib and endocrine therapy as adjuvant treatment in patients with HR+/HER2- early breast cancer: primary results from the phase III NATALEE trial. J Clin Oncol. 2023;41(suppl 17):LBA500. doi:10.1200/JCO.2023.41.17_suppl.LBA500
4. Woyach JA, Yin J, Brown JR, et al. Results of a phase 3 study of IVO vs IO for previously untreated older patients (pts) with chronic lymphocytic leukemia (CLL) and impact of COVID-19 (Alliance). J Clin Oncol. 2023;41(suppl 16):7500. doi:10.1200/JCO.2023.41.16_suppl.7500
5. Mellinghoff IK, van den Bent MJ, Blumenthal DT, et al. Vorasidenib in IDH1- or IDH2-mutant low-grade glioma. N Engl J Med. 2023;10.1056/NEJMoa2304194. doi:10.1056/NEJMoa2304194