Jennifer Woyach, MD, associate professor, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center–James, discusses ​the role of chemoimmunotherapy in chronic lymphocytic leukemia (CLL).

Recently, multiple positive phase 3 clinical trials have ​demonstrated superiority with novel agents compared with chemoimmunotherapy in CLL, says Woyach. In the clinic, the benefits and risk​s associated with chemoimmunotherapy, BTK inhibitors, and B​CL​-2 inhibitors must be discussed in great detail

Although FCR chemoimmunotherapy remains a standard treatment option for young, fit patients who do not have concerning genomic abnormalities, the regimen is being utilized less in the clinic. Moreover, patients tend to prefer alternative options, Woyach concludes. 

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Jennifer Woyach, MD, discusses ​the role of chemoimmunotherapy in chronic lymphocytic leukemia.

Dr. Woyach on the Role of Chemoimmunotherapy in CLL  

Howard A. “Skip” Burris, III, MD, FASCO, FACP, chief medical officer and president of Clinical Operations at Sarah Cannon Research Institute, 2019-2020 ASCO president-elect, and a 2014 Giant of Cancer Care® in Drug Development, discusses ​treatment considerations in triple-negative breast cancer (TNBC).

Patients with TNBC should be considered for clinical trials, says Burris. Notably, several emerging agents are showing encouraging data in the relapsed/refractory setting.

Moreover, it’s of critical importance for this group of patients to undergo molecular profiling because it can help identify 

or DNA damage repair mutations, high tumor mutational burden, or PD-L1 overexpression.

​Additionally, molecular information can inform therapy selection; thus, patients are encouraged to undergo molecular profiling, Burris concludes.

Howard A. “Skip” Burris, III, MD, FASCO, FACP, discusses ​treatment considerations in triple-negative breast cancer.

Dr. Burris on Treatment Considerations in TNBC  

Bradley J. Monk, MD, FACS, FACOG, US oncology medical director of Gynecologic Oncology Research and a professor at the University of Arizona College of Medicine, discusses emerging therapies in cervical cancer.

Early therapeutic intervention offers the best chance of survival in cervical cancer, explains Monk. Moreover, ​adding immunotherapy to chemoradiation for patients with unresectable locally advanced stage II and III disease could be a potentially promising approach.

Notably, the ​​phase 3 CALLA trial evaluating durvalumab (Imfinzi) plus chemoradiation and ​the phase 3 MK-3475-A18/KEYNOTE-A18/ENGOT-cx11 trial evaluating pembrolizumab (Keytruda) plus chemoradiation are ongoing global studies in this space.

The rationale for this research stems from the fact that chemoradiation can trigger an immune response. As such, the addition of a checkpoint inhibitor may result in a higher response rate compared with chemoradiation alone, Monk concludes.

Bradley J. Monk, MD, FACS, FACOG, discusses emerging therapies in cervical cancer.

Dr. Monk on Emerging Therapies in Cervical Cancer 

Hung Khong, MD, a breast oncologist within the Chemical Biology and Molecular Medicine Program at Moffitt Cancer Center, discusses the potential benefit of combining immunotherapy with endocrine therapy in estrogen receptor (ER)–positive, HER2-negative breast cancer.

ER-positive breast cancer is thought to be less aggressive compared with HER2-positive breast cancer and triple-negative breast cancer (TNBC), Khong explains. 

However, ER-positive breast cancer is associated with a longer risk of recurrence versus HER2-positive or, in particular, TNBC, Khong adds. 

If patients with TNBC have not recurred after 5 years, it is rare that recurrence will occur. Conversely, patients with ER-positive disease have a steady risk of relapse up to 30 years after diagnosis, says Khong.

As such, combining immunotherapy with endocrine therapy may offer patients with ER-positive disease long-term disease control, concludes Khong. 

Hung Khong, MD, discusses the potential benefit of combining immunotherapy with endocrine therapy in estrogen receptor–positive, HER2-negative breast cancer.  



Dr. Khong on the Potential Benefit of IO/Endocrine Therapy in ER+ Breast Cancer 

Betsy O'Donnell, MD, medical oncologist in the Multiple Myeloma Disease Center and director of Lifestyle Medicine, at Massachusetts General Hospital, discusses ongoing research efforts in multiple myeloma. 

Once therapies are shown to be safe and effective in the relapsed/refractory setting, they are typically evaluated in earlier lines of treatment, explains O’Donnell.

BCMA-targeted treatment and CAR T-cell therapy are two promising modalities in that regard, O’Donnell explains.

Novel combinations such as ixazomib (Ninlaro), lenalidomide (Revlimid), dexamethasone, and daratumumab (Darzalex) in transplant-ineligible multiple myeloma is also exciting as it could offer a mostly oral regimen for older patients, O’Donnell says. 

Other combinations such as carfilzomib (Kyprolis), lenalidomide, dexamethasone, and isatuximab-irfc (Sarclisa) are also under investigation in this space, concludes O’Donnell. 

Betsy O'Donnell, MD, discusses ongoing research efforts in multiple myeloma.  



Dr. O'Donnell Discusses Ongoing Research Efforts in Multiple Myeloma 

John A. Abraham, MD, FACS, founder, Orthopaedic Oncology Service, Rothman Orthopaedic Institute, and attending surgeon, Orthopaedic Surgery, Fox Chase Cancer Center, discusses key considerations regarding the management of tenosynovial giant cell tumor (TGCT).

Though rare, TGCT is a disease that should be kept in mind for patients who present with symptoms such as knee pain, Abraham says.

Diagnosing TGCT is typically based on symptoms and imaging, explains Abraham. As such, relying on a patient’s history, physical, and imaging is preferred to performing broad molecular panels for nondescript symptoms.

If a patient has TGCT, surgery remains the standard treatment, Abraham says. Additionally, patients may not need to see a medical oncologist upon diagnosis, but rather may be referred to a surgeon who can perform TGCT-related surgery. 

Beyond surgery, the recent approval of pexidartinib (Turalio) offers an oral treatment option for patients with symptomatic TGCT that is associated with severe morbidity or functional limitations and not responsive to improvement with surgery, concludes Abraham. 

John A. Abraham, MD, FACS, discusses key considerations regarding the management of tenosynovial giant cell tumor. 



Dr. Abraham on Key Considerations in the Management of TGCT 

Matthew S. Davids, MD, MMSc, director of clinical research in the Lymphoma Program and a medical oncologist with Dana-Farber Cancer Institute, as well as an assistant professor of medicine at Harvard Medical School, discusses ​remaining questions with umbralisib (TGR-1202) plus ibrutinib (Imbruvica) in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL).

The key takeaway from the longer-term follow-up on a phase 1/1b study (NCT02268851) examining the safety and efficacy of umbralisib in combination with ibrutinib in patients with CLL and MCL is that the initial results are holding up for the patients with CLL, with durable responses observed, says Davids. Moreover, higher rates of complete remission (CR) were reported with ibrutinib monotherapy, which was not expected.

There is currently some debate in the field right now on whether CRs are indicative of better outcomes for patients who are receiving a continuous therapy. These data are supportive of the possibility that achieving these deep reemissions can help sustain remissions for longer, as can be seen with the very impressive progression-free survival and overall survival data, according to Davids. However, longer-term follow-up data and comparative studies will be needed to answer that question more definitively, concludes Davids.

Matthew S. Davids, MD, MMSc, discusses ​remaining questions with umbralisib plus ibrutinib in chronic lymphocytic leukemia and mantle cell lymphoma.

Dr. Davids on Remaining Questions With Umbralisib/Ibrutinib in CLL and MCL

Paolo Ghia, MD, PhD, a professor of Medical Oncology and the director of the Strategic Research Program on CLL and the B Cell Neoplasia Unit at Università Vita-Salute San Raffaele University, discusses overall survival (OS) data with acalabrutinib (Calquence) in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) in the phase 3 ASCEND trial.

At the moment, an OS advantage was no observed with acalabrutinib compared with idelalisib (Zydelig) plus rituximab (Rituxan) or bendamustine plus rituximab, says Ghia. Nowadays, this is typical in the new trials because patients on the control arm, upon disease progression, had the opportunity to switch over to acalabrutinib, explains Ghia. This crossover affected the OS and showed the relevance of the treatment that is provided to these patients, concludes Ghia.

Paolo Ghia, MD, PhD, discusses overall survival data with acalabrutinib in patients with relapsed/refractory chronic lymphocytic leukemia in the phase 3 ASCEND trial.

Dr. Ghia on Lack of OS Advantage With Acalabrutinib Per ASCEND Trial in CLL

Debu Tripathy, MD, professor of medicine and chair of the Department of Breast Medical Oncology at The University of Texas MD Anderson Cancer Center, discusses fam-trastuzumab deruxtecan-nxki (Enhertu) versus ado–trastuzumab emtansine (T-DM1; Kadcyla) in HER2-expressing breast cancers.

Certain characteristics of trastuzumab deruxtecan are distinct from T-DM1, says Tripathy. One of the principal features in the laboratory and preclinical models is that trastuzumab deruxtecan is water soluble. When the antibody-drug conjugate is internalized into the tumor cell, it is slowly released into the microenvironment and can diffuse back out of the cells, explains Tripathy. Because of this functionality, the agent may also be able to impact other neighboring cells.

This ability is important because HER2 is not uniformly expressed on all tumors cells; some cells may express HER2 at a higher level than others, says Tripathy. Sometimes, when patients develop resistance to HER2–targeted therapies, the resistant subclone that grows has lost HER2 expression. Because trastuzumab deruxtecan can bind to lower-expressing HER2 cells, such as HER2 1+/2+, the agent may have an advantage over T-DM1, concludes Tripathy.

Debu Tripathy, MD, discusses fam-trastuzumab deruxtecan-nxki versus ado-trastuzumab emtansine in HER2-expressing breast cancers.

Dr. Tripathy on Trastuzumab Deruxtecan Versus T-DM1 in HER2-Expressing Breast Cancers

Ruben A. Mesa, MD, director of the Mays Cancer Center at UT Health San Antonio MD Anderson Cancer Center, discusses racial disparities in clinical trials for patients with myeloproliferative neoplasms(MPNs), myelodysplastic syndrome (MDS), and acute myeloid leukemia (AML).

Clinical trials for patients with MPNs, MDS, and AML lack diversity, says Mesa. Notably, these challenges are similar to those faced in solid tumor studies. 

Some contributing factors ​to the lack of diverse patient accrual include lack of access to clinical trials and financial limitations. 

Moreover, if travel is required, patients must have the financial flexibility to do so​, along with the ability to request time off of work. ​Lack of awareness and ​limited health literacy ​could also be barriers to enrolling a diverse group of patients, Mesa concludes. 

Ruben A. Mesa, MD, discusses racial disparities in clinical trials for patients with myeloproliferative neoplasms, myelodysplastic syndrome, and acute myeloid leukemia.

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