Winship

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.

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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 

Sagar Lonial, MD, FACP, professor and chair within the Department of Hematology and Medical Oncology and Anne and Bernard Gray Family Chair in Cancer at Emory University School of Medicine, as well as chief medical officer, Winship Cancer Institute of Emory University, discusses the benefits of early intervention in high-risk smoldering multiple myeloma (SMM).

Treatment for patients with SMM has undergone a great deal of change over the past few years, primarily due to the improved ability to identify risk stratification in different patient subgroups. Additionally, results from 2 randomized trials have demonstrated that a subset of patients should be offered early intervention, explains Lonial. 

This subset is the highest-risk smoldering myeloma subgroup, that is now categorized by the 20/20/20 criteria, published by the Mayo Clinic in 2018. Results from the QuiRedex trial evaluating lenalidomide (Revlimid) combined with low-dose dexamethasone demonstrated significant improvement in progression-free survival and overall survival in high-risk patient populations. These findings were corroborated by data from the recent ECOG-ACRIN trial, which showed similar benefit with regard to PFS, as well as a 91% risk reduction in the highest risk subset of patients.

Although many might not be open to the idea of early intervention, it is important that this is discussed with these patients and that they are offered the option of early therapy for the sake of prevention, concludes Lonial.

Sagar Lonial, MD, FACP, discusses the benefits of early intervention in high-risk smoldering multiple myeloma.

Dr. Lonial on the Importance of Early Intervention in High-Risk Smoldering Myeloma

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 impact of the coronavirus disease 2019 (COVID-19) on telehealth in head and neck cancer.

Telehealth has become an integral element of health care. Providers have begun to structure clinics so that patients who are healthy enough to be treated and managed remotely can do so through telehealth, says Saba.

In head and neck cancer, there are 2 groups of patients. Those who have good prognosis who may be in follow-up after definitive therapy or have stable disease. These patients are not receiving high-dose cytotoxic chemotherapy that would put them at high-risk of COVID-19, says Saba. Therefore, they can be seen remotely through telehealth.

However, patients who present with an acute illness that requires immediate care don’t necessarily have the luxury of using telehealth. These patients need to be managed in the clinic, says Saba, despite the added complications COVID-19 poses.

Dr. Saba on the Impact of COVID-19 on Telehealth in Head and Neck Cancer

The coronavirus disease 2019 (COVID-19) has created a unique set of challenges in the head and neck cancer paradigm, as related to the age and fitness of patients, the increased susceptibility to viral transmission through oral cavity examination, and the need for multidisciplinary treatment, according to Nabil F. Saba, MD, FACP.

Such challenges have led to the rapid implementation of telehealth, rotation schedule modifications for physicians, and new surgical guidance.

"We are adapting," said Saba. "As more time progresses, the more we are able to adapt to the situation. We are making changes that I believe will last even after the pandemic is gone. Sometimes it takes a crisis to induce people, including health care workers, to make the necessary changes to improve care for patients."

, Saba, director of the Head and Neck Medical Oncology Program at Winship Cancer Institute of Emory University, professor in the Department of Hematology and Medical Oncology and Department of Otolaryngology at Emory University School of Medicine, discussed how the COVID-19 pandemic has impacted treatment in head and neck cancer and the health care system at large.

 How has the COVID-19 pandemic altered your practice?

 Things have been drastically changing since the COVID-19 pandemic [started]. This has affected our day-to-day life in the cancer center and the way we practice. My schedule has completely changed. In regard to the clinic schedule, the rotation of physicians who are covering the clinic has changed. As you can imagine, it has really had a drastic effect on our patients.

At the cancer center, each of us spend a long time, every day, reviewing information, going over ways to implement new methods to try to overcome this [virus], and trying to cope with the current situation.

How has the virus impacted treatment plans for patients?

At the cancer center, we are trying to rely on telehealth. We are trying to structure the clinics so that patients who are healthy enough to be treated and managed remotely can take advantage of this possibility.

Regarding head and neck cancer, we really have 2 groups of patients. One group consists of patients who have relatively good disease. They may be in a follow-up period after definitive therapy or have advanced disease that is under control. [Those patients] are not getting high-dose cytotoxic chemotherapy that would put them at high-risk [of COVID-19]. Those patients are likely the best candidates for remote visits and telehealth.

The problem arises with patients who present with an acute illness that requires immediate care. We know that cancer in general is a dreadful disease and an inherently life-threatening condition. Therefore, when you add another life-threatening situation, such as COVID-19, it complicates matters for our patients who need acute intervention and care.

Patients with head and neck cancer need to be seen by multiple specialists. It's unlike other cancers. The blessing, but also the curse, of head and neck cancer is that it requires a multidisciplinary approach to treatment. We have the blessing of having multiple specialists taking care of patients. During this crisis, the surgical aspect has been affected to a great extent. Because of our multidisciplinary approach to treatment, many of these patients [have been] offered alternative modalities to surgery until a surgical approach can be offered.

In this period of time where social distancing is important, it becomes challenging to limit the health care team that is [allowed] in the clinic. We typically have multiple people in the same location trying to manage patients with acute problems.

This [issue] is compounded by the fact that head and neck cancer is inherently a disease where you need to examine the patient's oral cavity to look into the airway. We rely on that to be able to diagnose the disease and monitor patients.

If the patient's disease is relatively under control, it likely makes sense to follow them through telehealth. Additionally, there may be some ways to remotely examine patients' lesions.

However, when you are dealing with a newly diagnosed patient who has a life-threatening disease and requires immediate intervention, it becomes difficult to manage these patients through telehealth. Those patients need to be in the clinic for the initial evaluation and endure treatments that are already harsh for them in a normal situation. Now we are adding COVID-19 to the mix.

Surgery is taxing on the patient's day-to-day life, and the recovery period is slow and difficult. Daily radiation or chemoradiation for 6 weeks is also taxing.

In head and neck cancer, we don't have the luxury of de-intensifying therapy because our ultimate goal is to cure patients. When you have a patient who requires immediate intervention, deintensification is not really an option.

Have there been situations where you have been able to delay surgery or radiation in patients?

In general, we don't want to delay [treatment] because many of these patients need immediate care. However, we've been forced to delay interventions in many cases. Our surgical colleagues have been greatly affected by [COVID-19]. In the operating room, the nature of their work is to utilize the equipment [we need] to ration for the potential surge of patients who [present with] COVID-19.

In addition, there is a high risk when you manipulate and examine the patient's airway as we have seen from China and other countries. When you look into a patient's oral cavity during intubation, the chance of transmitting COVID-19 becomes high. This poses a major problem to those patients who require surgery.

We've created a sort of emergency mini-tumor conference where usually 3 of us representing surgery, medical oncology, and radiation oncology meet remotely on very short notice to briefly go over the cases that are scheduled for surgery or definitive therapy. Those are the most acute cases; we aren't talking about follow-ups or patients who are in progress.

We make decisions based on different factors, such as what is happening in the operating room and whether surgeries are allowed to happen that week. For example, this week has been better than 2 weeks ago when our operating rooms [limited patients from having] elective surgeries. This week, [surgeries] have been somewhat easier to schedule. Another factor is how acutely ill the patient is. When we look at different factors in a normal situation like the patient's age, and whether they are likely to tolerate the [proposed regimen], we need to see the patient.

We have been very busy not just dealing with COVID-19, but dealing with the ramifications of the virus on our patients.

Are you limiting the use of immunotherapy?

This is a very good question that we still need to learn more about. In head and neck cancer, we tend to use high-dose chemotherapy. However, high-dose chemotherapy, even though it is fairly toxic when you combine it with radiation, is not usually as immunosuppressive as the chemotherapy you would use in a patient with leukemia or breast cancer. We typically use cisplatin combined with radiation. The main toxicities include kidney toxicity, which we take care of by making sure the patient is well hydrated. Other common toxicities include neuropathy and hearing loss. Cisplatin in general is not very immunosuppressive because of these other limiting toxicities. In that sense, we are still somewhat blessed compared with some of our other colleagues.

However, I would say that we also deal with a patient population that has smoking-related cancers and patients who tend to have comorbidities linked to smoking. Of course, we have our HPV-positive patient population that is usually healthier and younger.

Additionally, because head and neck cancer tends to occur in an older patient population, these patients are at a higher risk of developing complications from COVID-19. They may have comorbidities that increase that risk as well.

Therefore, even though our treatment may not be as immunosuppressive, we are not dealing with a young, relatively healthy patient population. A large portion of patients with head and neck cancer tend to be older, frail, and at a high-risk of developing complications.

Your practice is based in Atlanta, Georgia. How has this city responded to the crisis?

Thus far in the Atlanta health care system, including our academic center at Emory University, it has been able to manage well, despite the fact that we have had a surge of patients with COVID-19. This surge has not broken the health care system or put us in a dire situation where we are not able to cope. We've been able to cope well.

I am hoping that because of the aggressive social distancing we've observing that things will continue to improve over the next few weeks.

The world is rapidly changing, and the world of communication is rapidly changing. We're able to at least communicate and keep in connection with our patients and colleagues. If it were not for [technology], we would be in a very different situation.

Additionally, health care and the treatment of patients with cancer is evolving. Those 2 worlds have to take advantage of what is happening in the world and implement these new tools to improve patient care and patient satisfaction. We've been forced to do that at some level [because of the current situation]. It is a good, healthy step for many cancer centers and for health care in general [to evolve with the times].

Is there anything else you would like to share?

It is important to remember different aspects of what we do in general. [The COVID-19 pandemic] has had an effect on our trainees, residents, and fellows. They are in a period of time where they need to [have as much hands-on learning] as possible. They need to see patients and be with the attending physicians to learn how to manage patients on a day-to-day basis.

I think we may have forgotten about this aspect, but it is an important aspect [of the conversation]. We're training the future physicians while we are dealing with this crisis. Our fellows and residents are stepping up to the plate to manage the situation, but because we are all under so much stress, we tend to not pay much attention to this.

Articles

Nabil F. Saba, MD, FACP, discusses how the COVID-19 pandemic has impacted treatment in head and neck cancer and the health care system at large.

COVID-19 Causes Major Treatment Modifications in Head and Neck Cancer

Ragini R. Kudchadkar, MD, associate professor, Department of Hematology and Medical Oncology, associate director, Hematology and Medical Oncology Fellowship Program-Clinical/Service, Emory University School of Medicine, Winship Cancer Institute, discusses the biological differences between ocular melanoma and cutaneous melanoma.

Ocular melanoma and cutaneous melanoma have biological differences that impact how patients respond to treatment, explains Kudchadkar.

Ocular melanoma generally metastasizes in the liver, says Kudchadkar. Additionally, ocular melanoma does not respond as well to immunotherapy and is associated with a poorer prognosis compared with cutaneous melanoma, explains Kudchadkar.

Currently, the primary means of treatment for patients with ocular melanoma is obtained through clinical trials, says Kudchadkar.

Ongoing phase 3 trials such as the FOCUS study and phase 2 trials such as the IMCgp100-202 study appear promising in developing novel treatments for patients with ocular melanoma, concludes Kudchadkar.

Ragini R. Kudchadkar, MD, discusses the biological differences between ocular melanoma and cutaneous melanoma.

Dr. Kudchadkar on the Biological Differences Between Ocular and Cutaneous Melanoma

Obese men with nonmetastatic prostate cancer have higher cardiovascular disease—related mortality and all-cause mortality, and potentially increased prostate cancer–specific mortality, according to findings published in the 

In the study, the distribution of 3855 patient deaths from all causes revealed 500 disease—specific deaths and 1155 cardiovascular disease–related deaths. Men who had an obese body mass index (BMI) ≥30 kg/m

 were more likely to experience prostate cancer—specific mortality versus men who had a healthy BMI of 18.5 < 25.0 kg/m

 (HR, 1.28; 95% CI, 0.96-1.67). Cardiovascular disease—related mortality was also heightened among obese men versus men at healthy weight (HR, 1.24; 95% CI, 1.03-1.49), translating to worse all-cause mortality (HR, 1.23; 95% CI, 1.11-1.35).

Moreover, men who gained >5% of their weight after diagnosis had a higher risk of prostate cancer—specific mortality versus those who maintained stable weight (+/- <3%; HR, 1.65; 95% CI, 1.21-2.25). This also translated into worse all-cause mortality among men who gained >5% of their body weight after diagnosis versus those who maintained stable weight (HR, 1.27; 95% CI, 1.12-1.45).

Men who were overweight at diagnosis and developed an obese BMI after diagnosis had a higher likelihood of prostate cancer—specific mortality (HR, 1.69; 95% CI, 1.12-2.57).

"Our results suggest that among survivors of nonmetastatic prostate cancer, postdiagnosis obesity may be associated with higher cardiovascular disease—related mortality and all-cause mortality," Alyssa N. Troeschel, MPH, and PhD candidate at Emory University, and coinvestigators wrote. "Postdiagnosis weight gain may be associated with a higher mortality as a result of all causes and prostate cancer," Troeschel and coinvestigators added.

In the analysis, men in the Cancer Prevention Study II Nutrition Cohort who were diagnosed with nonmetastatic prostate cancer between 1992 and 2013 were followed for mortality through 2016. Men who died within 4 years of follow-up were excluded from the analysis.

Patients' "baseline" BMI was taken from the first survey they completed within the first 6 years after diagnosis (n = 8330). Patients completed follow-up questionnaires every 2 years thereafter to track their change in weight (n = 6942).

Prostate cancer—specific mortality served as the primary endpoint of the trial. Key secondary endpoints included cardiovascular disease–related mortality and all-cause mortality.

The multivariable models used to calculate the association between BMI and mortality controlled for age, education, smoking status, physical activity, American Joint Committee on Cancer primary tumor category, Gleason score, initial treatment, and year of diagnosis. The weight change models also adjusted for patients’ postdiagnosis BMI in the calculation.

In the BMI cohort, 36% of men were of healthy weight, 49% were overweight, and 16% were determined to be obese.

Although the mortality rate was most pronounced in obese men, overweight men also demonstrated a higher risk of prostate cancer—specific mortality (HR, 1.23; 95% CI, 1.00-1.50), but not cardiovascular disease–related mortality or all-cause mortality.

"Survivors of prostate cancer are advised to maintain a healthy weight and avoid weight gain, and our findings provide additional evidence to follow these recommendations," Troeschel and coinvestigators wrote.

Notably, obesity was associated with a higher likelihood of prostate cancer—specific mortality in men with low-risk tumors (HR, 1.58; 95% CI, 1.13-2.22) but not high-risk tumors (HR, 1.00; 95% CI, 0.63-1.58). Although the relationship between BMI and prostate cancer–specific mortality was stronger in men with low-risk tumors, the association between risk category and BMI was not statistically significant (

In the weight change cohort, all-cause mortality was also heightened in men who lost 3% to 5% of their body weight (HR, 1.15; 95% CI, 1.02-1.31) and in men who lost >5% of their body weight (HR, 1.30; 95% CI, 1.16-1.46). There was no association between weight change and cardiovascular disease—related mortality.

Additional analyses that accounted for other potential confounding variables, such as treatment course, revealed similar findings.

"Future studies are needed to determine whether intentional weight loss provides health benefits among overweight and obese survivors of prostate cancer. Clinicians should be vigilant about identifying moderate weight loss or gain in survivors of prostate cancer because both have poor prognostic implications," Troeschel and coinvestigators concluded.

Postdiagnosis body mass index, weight change, and mortality from prostate cancer, cardiovascular disease, and all causes among survivors of nonmetastatic prostate cancer [published online ahead of print April 6, 2020]. 

Obese men with nonmetastatic prostate cancer have higher cardiovascular disease–related mortality and all-cause mortality, and potentially increased prostate cancer–specific mortality.

High BMI, Weight Gain Tied to Increased Mortality in Prostate Cancer

Advances have been few and far between in metastatic ocular melanoma, explained Ragini Kudchadkar, MD. However, as ongoing research unfolds, the field may be able to couple these findings with optimal patient selection to improve outcomes.

Patients with metastatic ocular melanoma have a poor prognosis. However, findings from a retrospective study showed that patients with ocular melanoma that is metastatic to the liver experienced prolonged progression-free survival (PFS) and overall survival (OS) if they had an ECOG performance status of 0 and received concurrent yttrium-90 (Y-90) and immunotherapy.

Among 24 patients who received immunotherapy within 3 months of undergoing Y-90, the median OS was 26 months versus 9.5 months for others (

 = .014). For patients with an ECOG performance status of 0, the median OS was 26 months versus 5.5 months for others (

 = .003). The median hepatic PFS was 10.3 months with Y-90 on concurrent immunotherapy versus 2.7 months in patients who received transarterial radioembolization only (

“We're all trying to understand where liver-directed therapy lies in patients with melanoma, as we are combining these liver-directed therapies with traditional immunotherapies. The study shows that you can use liver-directed therapies along with other therapies to help improve outcomes for specific populations of patients,” said Kudchadkar, a co-author of the study.

, Kudchadkar, associate professor, Department of Hematology and Medical Oncology, associate director, Hematology and Medical Oncology Fellowship Program-Clinical/Service, Emory University School of Medicine, Winship Cancer Institute, discussed the prognosis of patients with metastatic ocular melanoma and the work being done to define novel approaches in the space.

: Could you discuss the overall prognosis for patients with ocular melanoma? 

: Ocular melanoma is a different “beast” than cutaneous melanoma. The biology of ocular melanoma is very different in the sense that it primarily metastasizes to the liver, though it can go other places. Responses to traditional therapies, such as immunotherapy, are nowhere near the degree of responses in cutaneous melanoma, so patients’ prognosis is much more guarded. In ocular melanoma, we haven't made anywhere near the advancements we have made in cutaneous melanoma.

What is the state of treatment in ocular melanoma?

Right now, the primary treatment for patients with metastatic ocular melanoma is clinical trials. There are a lot of novel agents that are in the pipeline. There are 2 big phase III trials that are ongoing right now: one from [Delcath Systems with perfusion] with liver-directed chemotherapy and 1 with glycoprotein 100 versus standard of care, immunotherapy. Both trials are showing promise, and I'm very hopeful that there's more to come.

Could you discuss additional research in this space?

The 2 targets in clinical trials have been these novel immunotherapies. We’re also trying to target different gene mutations that lead to upregulation of the MEK pathway. Many MEK inhibitors have been tested, but we have yet to make a significant impact on the PFS of patients with this disease.

You co-authored a study on predictors of OS and PFS with Y-90 radioembolization in patients with ocular melanoma that is metastatic to the liver. What did the results of that study show? 

The study showed that patients with metastatic ocular melanoma to the liver can undergo a liver-directed therapy to help control disease. Volume of disease and function of the liver are probably the biggest predictors of how well patients do with this procedure. Isolated metastases in patients with good overall liver function do the best.

Is there any other research in this space that you're excited about? 

There has been a lot of excitement in skin cancers outside of melanoma. Traditionally, medical oncologists haven't been involved in the care of patients with Merkel cell carcinoma, squamous cell carcinoma, and basal cell carcinoma. It's very exciting to know that there are a lot of new immunotherapies and targeted therapies for patients with these diseases.

The multidisciplinary team should now include medical oncologists. We have a lot more options [beyond] surgery and radiation, which we perform with curative intent, [for] the small portion of patients that have more advanced disease.

The role of treatments in melanoma and non-melanoma skin cancers has dramatically improved as [have our biomarkers of response to these agents]. I'm really interested in biomarkers and how to address resistance to these therapies in advanced melanoma. Unfortunately, a group of patients still don’t respond to our therapies, [so we have more work to do].

Levey AO, Elsayed M, Lawson D, et al. Predictors of overall and progression-free survival in patients with ocular melanoma metastatic to the liver undergoing Y90 radioembolization. 

. 2020;43(2):254-263. doi: 10.1007/s00270-019-02366-8.

Ragini Kudchadkar, MD, discusses the prognosis of patients with metastatic ocular melanoma and the work being done to define novel approaches in melanoma.

Ongoing Research Efforts in Metastatic Ocular Melanoma Could Shift Paradigm

Walter J. Curran, Jr, MD, FACR, FASCO, executive director of Winship Cancer Institute of Emory University, associate vice president of Cancer at Woodruff Health Sciences Center, and Lawrence W. Davis Chair of Radiation Oncology at Emory University School of Medicine, explains the eligibility criteria for immunotherapy and radiation in patients with lung cancer.

Any fit patient with stage III lung cancer who comes out of chemoradiation in good condition without evidence of disease progression should be considered for adjuvant durvalumab (Imfinzi), irrespective of PD-L1 status, explains Curran.

In the metastatic setting, although no standard of care exists, ongoing clinical trials are examining the integration of high-dose radiation with immunotherapy, says Curran. Furthermore, the opportunity for stereotactic body radiation therapy is in the clinical trial setting, concludes Curran.

Walter J. Curran, Jr, MD, FACR, FASCO, explains the eligibility criteria for immunotherapy and radiation in patients with lung cancer.

Dr. Curran on the Integration of Immunotherapy With Radiation Therapy in Lung Cancer

Sagar Lonial, MD, FACP, professor and chair, Department of Hematology and Medical Oncology, Emory University School of Medicine, chief medical officer, Winship Cancer Institute of Emory University, discusses the role of targeted therapy in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).

-mutant AML as well as emerging data with monoclonal antibodies, bispecific T-cell engagers, and bispecific antibodies are changing the treatment paradigm in AML, says Lonial.

Targeted therapy has shifted the treatment paradigm of AML away from standard 7+3 chemotherapy to become more personalized.

In ALL, similar data have emerged with novel CD19- and CD22-directed therapies, says Lonial.

Additionally, the use of minimal residual disease status in ALL may shed light on which patients should undergo an allogeneic stem cell transplant, Lonial concludes.

Sagar Lonial, MD, FACP, discusses the role of targeted therapy in acute myeloid leukemia and acute lymphoblastic leukemia.

Dr. Lonial on the Role of Targeted Therapy in AML and ALL

Belantamab mafodotin is emerging as a novel BCMA-targeted therapeutic option to treat patients with heavily relapsed/refractory multiple myeloma, a population that continues to be an unmet need, explained Sagar Lonial, MD, FACP.

The DREAMM-1 trial evaluated the safety, pharmacokinetics, pharmacodynamics, immunogenicity, and clinical activity of belantamab mafodotin in patients with relapsed/refractory myeloma and other advanced BCMA-expressing hematologic malignancies. These data elicited an overall response rate (ORR) of 60.0%, with 3 complete responses (CRs) and 2 stringent CRs.1 The median progression-free survival (PFS) was 12 months (95% CI, 3.1—not estimable), and the median duration of response was 14.3 months (95% CI, 10.6-NE).

The DREAMM-2 trial compared different doses of belantamab mafodotin in patients with relapsed/refractory myeloma. The agent showed an ORR of 31% (97.5% CI, 20.8-42.6) in patients receiving the recommended 2.5-mg/kg dose. In those who received belantamab mafodotin at 3.4 mg/kg, the ORR was 34% (97.5% CI, 23.9-46.0).

Based on the DREAMM-2 data, the FDA granted a priority review designation to belantamab mafodotin in January 2020 as a treatment for patients with relapsed/refractory multiple myeloma who received prior therapy with an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 agent.

“Having an off-the-shelf BCMA targeted therapy is a really easy and simple way to talk about treating [patients] when you don't have a lot of other options,” said Lonial. “I suspect other [BCMA-targeted therapies] will start to move [into] the treatment paradigm as well.”

Data show that belantamab mafodotin is associated with ocular adverse events (AEs), which are typically manageable with supportive care and dose modifications. Monitoring and treating these AEs allows patients to continue with treatment, sometimes with a brief pause.

The next steps to take with belantamab mafodotin will involve searching for other agents to pair with the antibody-drug conjugate (ADC).

, Lonial, professor and Anne and Bernard Gray Family Chair in Cancer at Emory University School of Medicine, as well as chief medical officer at Winship Cancer Institute of Emory University, discussed the encouraging activity with the BCMA-targeted agent belantamab mafodotin in multiple myeloma.

: What novel therapies are being explored in multiple myeloma?

: The novel approaches involve the use of BCMA-targeted therapy, including ADCs—such as belantamab mafodotin&mdash;bispecific antibodies, or CAR T-cell therapy. [BCMA] is the next new big target in myeloma. We are trying to figure out the best approach, when to use [these BCMA-targeted therapies], and how to maximize their benefit to eventually discuss curing patients.

How will ADCs transform the myeloma landscape?

ADCs, particularly those targeting BCMA, have the ability to come off the shelf, meaning you don't have to wait for [the ADCs] to be available. They don't necessarily have the inpatient hospitalization that you might see with bispecific T-cell engagers (BiTEs) in terms of cytokine release syndrome (CRS) or other potential complications. As we're learning from early-phase studies, [ADCs] are able to be combined with other standard anti-myeloma drugs. Figuring out how to use [ADCs] and position them in a way that is effective immediately and can translate into long-term immunity is an exciting part of ADCs.

Could you discuss the DREAMM-1 and DREAMM-2 trials and their impact on the paradigm?

What we know about belantamab mafodotin comes from 2 trials: DREAMM-1 and DREAMM-2. The first was the DREAMM-1 study, which was a phase I trial designed to identify the dose that should go forward in trials. We saw that the ORR was around 60%. The median PFS was somewhere between 11 and 12 months. In that same trial, if you look at a penta-refractory patient population, these numbers are much smaller [compared with the overall DREAMM-1 population]. We demonstrated that the response rate was somewhere around 35% to 40% and the median PFS was around 4 months.

In DREAMM-2, we tested 2 different doses of belantamab mafodotin. One dose was 2.5 mg/kg and the other was 3.4 mg/kg; we tried to identify which was the safer dose to move forward. The ORR was relatively similar, at about 30% in both cohorts, which is similar to what we have seen for every other approved drug in the refractory myeloma setting. The median PFS is somewhere around 3 months. It looks like the duration of response is going to be much longer, suggesting that the responses patients get are durable.

If you begin to look at AEs, there were 2 big categories that came up. One was ocular toxicity, which can be managed with dose modifications and adjustments. The second was hematologic toxicity, which was not unexpected, given that it's an ADC. The hematologic toxicity is easily manageable by most hematologists and belantamab mafodotin hopefully will be a very active drug for us. The ability to combine belantamab mafodotin with other drugs is what we're looking at in current trials.

You want to partner with an ophthalmologist who can give you some early clues as to what's going on in the cornea, and then make decisions based on symptoms and AEs—regarding whether you want to hold the dose, give the dose, make dose adjustments, or dose modifications. Those are probably the biggest issues. Much of the other toxicity is infusion related, which is standard for most of us in hematology. There is also thrombocytopenia or hematologic toxicity, which most of us are used to dealing with in this disease.

If belantamab mafodotin receives FDA approval, what impact will it have on the myeloma landscape?

As good as we've gotten in myeloma, unfortunately, there still are a lot of patients who run out of available treatment options. Having something for those heavily relapsed and refractory patients will be a huge step forward.

What are the next steps of this research with belantamab mafodotin?

Beyond FDA approval, the next steps include combining belantamab mafodotin with standard drugs, such as bortezomib (Velcade), lenalidomide (Revlimid), pomalidomide (Pomalyst), and carfilzomib (Kyprolis). There are also other studies combining belantamab mafodotin with checkpoint inhibitors to see whether or not you can take that immunogenic cell death and use that to spur on an immune response that may last longer than the time that you're giving the drug. That is an exciting concept if we can prove that it works.

Trudel S, Lendvai N, Popat R, et al. Antibody—drug conjugate, GSK2857916, in relapsed/refractory multiple myeloma: an update on safety and efficacy from dose expansion phase I study. 

. 2019;9(37). doi: 10.1038/s41408-019-0196-6           

Lonial S, Lee HC, Badros A, et al. Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study. 

 2020;21(2):207-221. doi: 10.1016/S1470-2045(19)30788-0

Sagar Lonial, MD, FACP, discusses the encouraging activity with the BCMA-targeted agent belantamab mafodotin in multiple myeloma.