Greenberger Uncovers Noteworthy Updates and Triumphs in Hematology

Lee Greenberger, PhD

The year 2023 witnessed transformative updates in hematologic malignancies, including the exciting progress in sickle cell therapies, the developing field of cellular therapy, and the use of quadruplet combinations. At the 2023 American Society of Hematology Annual Meeting (ASH), several exciting updates were brought to the forefront.

According to Lee Greenberger, PhD, 1 trial that particularly commanded attention at ASH was the phase 3 PERSEUS study (NCT03710603) which showed that subcutaneous daratumumab (Darzalex) followed by autologous stem cell transplant and daratumumab, bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (D-VRd) consolidation and daratumumab/lenalidomide maintenance in newly diagnosed, transplant-eligible multiple myeloma significantly improved progression-free survival (PFS). At 4 years, the PFS was 84.3% with D-VRd vs 67.7% with VRd, and a 58% reduction in the risk of disease progression or death was observed (HR, 0.42; 95% CI, 0.30-0.59; P <.0001).¹

Greenberger, chief scientific officer, The Leukemia & Lymphoma Society (LLS) also noted work done through LLS, particularly new data from 2 master clinical trials: PedAL (NCT04726241) and the Beat AML Master Clinical Trial (NCT03013998). Both studies aim to fundamentally change the ways in which pediatric and adult patients with acute leukemias are treated.

Additionally, he noted the emergence of a new target in mantle cell lymphoma (MCL) through chimeric antigen receptor (CAR) T-cell therapy which has become a significant development in the space.

Looking ahead to 2024, Greenberger addresses key considerations for community oncologists and recognizes the importance of participating in clinical trials. According to Greenberger, a pivotal aspect of this effort is the IMPACT hub-and-spoke model initiated by LLS which works to bridge the gap between major medical centers and community settings.² Through this innovative approach, experts hope to enhance treatment responses for patients with cancer and serve underserved communities in need of advanced therapies.

In an interview with Targeted Oncology^TM, Greenberger, discussed some of the latest, interesting research that caught his attention in 2023 and what community oncologists should know about the space as we move into 2024.

blood cells : © Dr_Microbe - stock.adobe.com

What were some of the studies presented at ASH 2023 that caught your attention?

Greenberger: There are many studies that look quite promising. There are new studies in AML [acute myeloid leukemia]. [In 2023], we've seen approvals of quizartinib [Vanflyta], we've seen another [isocitrate dehydrogenase] inhibitor get approved, and what is particularly exciting is the Menin inhibitor story. That began at LLS. Over 15 years ago, the first Menin inhibitor [was] developed and it went from our academic grant program to our venture philanthropy program, and Syndax [Pharmaceuticals] now has another menin inhibitor. Those phase 1 and 2 data look quite encouraging.

The important thing is it will be a brand-new molecular mechanism of action for an AML-directed therapy History will tell you that AML is a heterogeneous disease and you're going to have to attack it from multiple angles. Menin-MLL inhbitors are going to give us another angle to attack AML. [Menin] is a fusion protein that we know drives the disease. There are also indications in the NPM1 status, which can be also related to the response rate.

The imetelstat [GRN163L] data looking at transfusion dependencies in the phase 3 trial is exciting [as well as] the daratumumab quadruplet therapy compared with the triplet therapy which is giving a better response rate. Daratumumab is already approved and so now, combining it in newly diagnosed with the conventional agents, leads tomproved progression-free survival- compared to just the conventional agents sets the stage for a new standard of care. .

A couple of other programs look interesting to me. One is that there is a new target in mantle cell lymphoma. This is a program that has been in the works for 5 years. Dr. Larry Kwak and colleagues are reporting data on a CAR T which has efficacy in MCL. It is in the early days, but it looks like another target for the CAR T cells and I look forward to getting more patients on therapy.

What should community oncologists be aware of regarding the hematology space moving into 2024?

We are aware of many patients in the community that need therapies or should be getting at least consulted with expert advice. First, by definition, all blood cancers are rare with under 200,000 patients a year. Moverover, there are over 100 types of blood cancer. Some of these blood cancers are exceptionally rare where new cases in the US occur at 1000 patient per year. The community oncologist, who may even be a heme/onc specialist, rarely encounter patients with exceptional rare blood cancers.

One of LLS’s goals is to educate patients and physicians in the community and tell them that there may be better therapy options, some may be experimental therapy, and getting these patients on this experimental therapy will give better output. Along those lines, what we did about 10 years ago was a hub-and-spoke model with Dana Farber [Cancer Institute] as the hub, and it went out to the folks around the [United States]. That was the precursor to a program we call IMPACT.

We now have 7 IMPACT hub-and-spoke models. The hub is a major medical center, the spokes are all out in the community. The ultimate concept is to put the clinical trial out in the community with a hub as basically the overseer because we would like to get medicines out to the community setting and do clinical trials in the community setting. Not only will that hopefully [lead to] better responses out in the community, but it is also will get to the underserved community that seeks optimal care.

REFERENCES

1. Sonneveld P, Dimopoulos MA, Boccadoro M, et al. Phase 3 randomized study of daratumumab + bortezomib, lenalidomide, and dexamethasone (VRd) versus VRd alone in patients with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplantation: primary results of the PERSEUS trial. Blood. 2023;142(suppl 2):LBA1. doi:10.1182/blood-2023.191911

2. Collaboration driving progress: LLS forms alliances with leading cancer institutions and foundations to co-Fund nearly $17 million in new research grants. News release. The Leukemia & Lymphoma Society. December 14, 2020. Accessed January 9, 2024. http://tinyurl.com/mcuujkwk