Reem Karmali, MD, MS, an assistant professor of medicine (hematology and oncology) at Northwestern University's Feinberg School of Medicine, discusses next steps for optimizing maintenance therapy in older patients with mantle cell lymphoma (MCL).

An analysis examining clinical outcomes and predictors of survival in older patients with MCL in the era of rituximab (Rituxan) was presented at the 

. With respect to the future, the big question is how to optimize maintenance approaches for older patients with the disease, says Karmali. In a trial at Northwestern University’s Feinberg School of Medicine,investigators are examining ibrutinib (Imbruvica) maintenance therapy for up to 4 years in patients of all age groups, including those who are older. Some insight may be gained regarding whether single-agentibrutinib as maintenance would be beneficial in this particular patient population, explains Karmali.

Other ongoing trials are examining therapeutic strategies specifically in older patients with MCL, adds Karmali, one of which is the phase 3 SHINE study. In this study, patients with MCL over the age of 65 are being treated with bendamustine/rituximab (Rituxan) as a backbone with or without ibrutinib. Investigators are also addressing whether ibrutinib with rituximab versus rituximab monotherapy as a maintenance strategy would be useful.

Another European trial, the phase 3 MCL R2 Elderly trial, is being conducted to see whether lenalidomide (Revlimid) is an appropriate strategy for the maintenance setting. Many ongoing trials will address optimization of maintenance approaches in elderly patients with the disease, concludes Karmali.

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Reem Karmali, MD, MS, discusses next steps for optimizing maintenance therapy in older patients with mantle cell lymphoma.

Dr. Karmali on Optimizing Maintenance Therapy in Older Patients With MCL

Preetesh Jain, MD, PhD, clinical fellow in medical oncology at The University of Texas MD Anderson Cancer Center, discusses research efforts examining resistance patterns with venetoclax (Venclexta) in mantle cell lymphoma (MCL).

The findings from a small prospective study indicated that venetoclax-based therapy was highly effective in patients with high-risk MCL and acquired resistance to the agent was predominantly associated with non–BCL-2 mutations. These findings need further validation in a larger cohort of prospectively collected samples, says Jain. Similar types of analyses in other ongoing trials with venetoclax and ibrutinib (Imbruvica) in the frontline setting are also being conducted to understand the pattern of resistance to the agent in less heavily pretreated patients.

To do this, pretreatment samples will need to be collected and studied. In the phase 1 study, the pretreatment samples had been previously treated with other agents, such as ibrutinib or chemotherapy, making the pretreatment clonal evolution data not indicative of what an untreated sample would look like.

Even in patients with poor-risk MCL, the response rate with venetoclax was very impressive. These findings are very provocative, according to Jain, even though it was a retrospective study that had enrolled a small number of patients with limited samples available for whole-exome sequencing. These are preliminary findings, which will potentially lead to studying this particular pattern of resistance in a larger number of samples, concludes Jain.

Preetesh Jain, MD, PhD, discusses research efforts examining resistance patterns with venetoclax in mantle cell lymphoma.

Dr. Jain on Future Research Efforts Examining Venetoclax Resistance Patterns in MCL

Justin Moyers, MD, a fellow in hematology and oncology at Loma Linda University Cancer Center, discusses real-world data and sociodemographic factors from an early analysis of the National Cancer Database (NCDB) associated with the treatment of adjuvant immunotherapy in stage III melanoma.

, survival curves and demographic data from the database were presented, says Moyers. As there has only been approximately 2 to 3 years of follow-up for these patients in the NCDB, landmark 24-month survival was studied in patients with all stages of disease. Additionally, since median survival data could be reported specifically for patients with stage IIIC disease, those results were also presented. The 24-month survival for all-comers was 83% for immunotherapy received versus 80% for immunotherapy not given, which was close to being statistically significant with a 

The 24-month survival data by substages were also reported, adds Moyers. Patients with stage IIIC disease who received adjuvant immunotherapy had a statistically significant improvement in survival compared with those who did not receive the treatment, at 70% versus 59%, respectively (

<.01). Although survival rates were still higher in those with stage IIIA and stage IIIB disease who received immunotherapy after surgery, the benefit did not reach statistical significance. The rates for immunotherapy-treated patients with stage IIIA and stage IIIB disease were 94% and 84%, respectively, versus 91% and 81%, respectively, for those who did not receive the treatment.

Furthermore, the overall survival of patients with stage IIIC disease was estimated to be 32.8 months for those who received adjuvant immunotherapy versus 28.0 months for those who did not receive immunotherapy. It is important to note that these are early data and a more precise estimation is expected in the future, concludes Moyers.

Justin Moyers, MD, discusses real-world data and sociodemographic factors from an early analysis of the National Cancer Database associated with the treatment of adjuvant immunotherapy in stage III melanoma.

Dr. Moyers on Real-World Data With Adjuvant Immunotherapy in Melanoma

Sheila Figel, PhD, a neuro-oncologic scientist with Roswell Park Cancer Institute, discusses preclinical research with canonical and noncanonical survivin isoforms that are displayed on the surface of cancer cells.

For their research, Figel and colleagues set out to express the different types of transcripts in multiple cell type backgrounds, including an embryonic cell line that was representative of developmental tissue (HAK 293), and several tumor cell lines, which included cervical adenocarcinoma and glioblastoma.

When this was done across different cell lines, investigators found that in addition to the canonical isoform, the Δex3 and 2B isoforms of survivin, which are known to be expressed in different cancer types, were being shuttled to the plasma membrane and were being expressed on the outside of cancer cells. This indicates that since this can be observed in the system, it is possible that this is also happening in real tumors within patients. This theory will be further examined in a follow-up study, Figel adds.

Additional findings were reported from analyses that focused on sequence of the isoforms. The isoforms differ in their C-termini but they share the Baculovirus IAP Repeat domain, which is known to have a role in antiapoptosis or survival, Figel explains. Investigators theorized that cutting off certain domains within the isoforms would impact the localization and that a flow assay could be used as a read out for that. However, results showed that canonical isoform 1 does not appear to require its dimerization for translocation to take place, nor does it appear to require the first 10 amino acids, which are needed for dimerization and mitochondrial targeting, Figel concludes.

Sheila Figel, PhD, a neuro-oncologic scientist with Roswell Park Cancer Institute, discusses preclinical research with canonical and noncanonical that are displayed on the surface of cancer cells.

Dr. Figel on Preclinical Research With Survivin Isoforms in Cancer Cells

Nabil F. Saba, MD, FACP, director, Head and Neck Medical Oncology Program, Winship Cancer Institute of Emory University, professor, Department of Hematology and Medical Oncology, Department of Otolaryngology, Emory University School of Medicine, discusses the future of treatment in head and neck cancer.

The introduction of immunotherapy to the head and neck cancer paradigm significantly improved outcomes for patients while maintaining quality of life, explains Saba.

However, the question of whether patients who progress on first-line immunotherapy can be resensitized to receive immunotherapy remains unclear, says Saba.

Determining the optimal sequencing strategy and combination regimen is critical to push the field forward. However, Saba predicts pembrolizumab will not be challenged as a standard of care for at least 1 year.

Nabil F. Saba, MD, FACP, discusses the future of treatment in head and neck cancer.



Dr. Saba on the Future of Treatment in Head and Neck Cancer 

John Kuruvilla, MD, FRCPC, clinician investigator, Cancer Clinical Research Unit, Princess Margaret Cancer Centre, discusses the broad utility of pembrolizumab (Keytruda) in Hodgkin lymphoma.

At the 2020 ASCO Virtual Scientific Program, findings from the phase 3 KEYNOTE-204 trial demonstrated a 35% reduction in the risk of disease progression or death with pembrolizumab compared with brentuximab vedotin (Adcetris) in patients with classical Hodgkin lymphoma who relapsed post-transplant or were ineligible for transplant.

Moreover, the progression-free survival benefit with pembrolizumab was observed across prespecified patient subgroups.

Biomarkers were not included in this study as there no well-defined predictive targets in Hodgkin lymphoma, explains Kuruvilla.

As such, pembrolizumab may broadly apply to patients in this population who fit the inclusion criteria and have relapsed following or who are ineligible for transplant, concludes Kuruvilla.

John Kuruvilla, MD, FRCPC, discusses the broad utility of pembrolizumab in Hodgkin lymphoma.



Dr. Kuruvilla on the Broad Utility of Pembrolizumab in Hodgkin Lymphoma

Brian T. Hill, MD, PhD, director of the Lymphoid Malignancies Program and staff physician, Taussig Cancer Institute, and assistant professor, Hematology and Oncology, Cleveland Clinic, discusses the safety profile of selinexor (Xpovio) in relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

On June 22, 2020, the FDA approved selinexor for the treatment of patients with relapsed/refractory DLBCL, not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 prior lines of systemic therapy.

The approval is based on findings from the phase 2b SADAL trial, in which patients were administered oral selinexor twice weekly at a dose of 60 mg or 100 mg, explains Hill.

Regarding safety, common adverse effects that were observed with the 100 mg dose were nausea, anorexia, diarrhea, fatigue, constipation, vomiting, and pyrexia, says Hill. The approval is for the 60 mg dose.

Supportive care measures such as antiemetics and appetite stimulants may alleviate some of these toxicities and allow patients to remain on treatment for extended periods of time, concludes Hill.

Brian T. Hill, MD, PhD, discusses the safety profile of selinexor in relapsed/refractory diffuse large B-cell lymphoma.

Dr. Hill on the Safety Profile of Selinexor in Relapsed/Refractory DLBCL

Alexandra Sokolova, MD, a hematology/oncology fellow of the University of Washington, discusses the challenges of germline testing in patients with metastatic prostate cancer. 

The lack of infrastructure to facilitate efficient germline testing is an unmet need, says Sokolova. Traditionally, ​when patients aresent to a genetic counselor, they must undergo pre-test counseling, germline testing, and post-test counseling.

This method can be time consuming, and there is a lack of available resources to provide this service to eligible patients. Providingan alternative model that could help them streamline the resources could lead to better care for their patients, Sokolova adds. 

In an IRB-approved prospective trial, genetic counseling was conducted through video meetings. This method appeared effective, especially when the patients were comfortable with the ​genetic provider, Sokolova concludes.

Alexandra Sokolova, MD, discusses the challenges of germline testing in patients with metastatic prostate cancer. 

Dr. Sokolova on Challenges of Germline Testing in Metastatic Prostate Cancer

David O'Malley, MD, a professor in the Department of Obstetrics and Gynecology at the Ohio State University (OSU) College of Medicine; and director of the Division of Gynecologic Oncology; director of Clinical Research in Gynecologic Oncology; and co-director of the Gynecologic Oncology Phase I Program at The OSU Comprehensive Cancer Center–James, discusses the utility of mirvetuximab soravtansine (IMGN853) in ovarian cancer.

Historically, mirvetuximab has been shown to be continuously beneficial in multiple areas of treatment, most notably in platinum-resistant ovarian cancer, says O’Malley. However, data have also been previously reported on mirvetuximab combined with carboplatin and bevacizumab (Avastin) and exciting data have been reported with this triplet combination, adds O’Malley.

Now, mirvetuximab may offer an opportunity to replace paclitaxel in the ovarian cancer space. It is well-known that paclitaxel causes several adverse events, such as alopecia and neuropathy, and it is possible that mirvetuximab could replace it as a better option with less toxicity and potentially improved efficacy, concludes O’Malley.

David O'Malley, MD, discusses the utility of mirvetuximab soravtansine in ovarian cancer.

Dr. O’Malley on the Utility of Mirvetuximab in Ovarian Cancer

Leora Horn, MD, MSc, Ingram Associate Professor of Cancer Research; associate professor of medicine (Hematology and Oncology); assistant director of the Educator Development Program and clinical director of the Thoracic Oncology Program at Vanderbilt-Ingram Cancer Center, discusses data from an updated analysis of the phase 3 IMpower133 trial, which examined the first-line combination of atezolizumab (Tecentriq), carboplatin, and etoposide in small cell lung cancer (SCLC).

Results from an exploratory analysis of IMpower133 presented during the 2020 AACR Virtual Annual Meeting showed that the combination continued to improve overall survival (OS) compared with chemotherapy alone in the frontline treatment of patients with extensive-stage SCLC, regardless of PD-L1 and blood tumor mutational burden (TMB) status.

One important thing to remember withseveral trials evaluating checkpoint inhibitors, Horn notes, is that oftentimes investigators are focusing on the tail of the curve and trying to understand whether patients are experiencing long-term survival. With longer follow-up, results showed that the triplet regimen continued to have an OS benefit, at 12.3 months with a hazard ratio of 0.76. Additionally, the 18-month OS was found to be 13% higher in patients treated with the triplet versus those given chemotherapy alone, at 34% versus 21%.

Updated results related to PD-L1 expression and TMBand and how these factors might help to predict outcomes with checkpoint inhibitor therapies were also presented. In the original publication, investigators examined blood TMB using cutoffs of both 10 and 16 and found that this factor did not serve as a predictor of response or survival with checkpoint inhibitor therapy. A benefit was observed in patients with high TMB and low TMB, Horn concludes.

Leora Horn, MD, MSc, discusses data from an updated analysis of the phase 3 IMpower133 trial, which examined the first-line combination of atezolizumab (Tecentriq), carboplatin, and etoposide in small cell lung cancer.