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Mehmet Akce, MD, is a hematologist/oncologist and associate professor at the University of Alabama. 

Mehmet Akce, MD, discusses how he treats patients with advanced hepatocellular carcinoma in the first-line setting.

Addressing How to Treat Patients With Advanced Hepatocellular Carcinoma

ASH 2024 Preview for Community Oncologists: The Show and After Show

The American Society of Hematology (ASH) Annual Meeting and Exposition aims to educate oncology providers across an array of hematologic malignancies, with a focus on novel agents, drugs across the FDA pipeline, and more.

, co-hosts Kristie L. Kahl and Andrew Svonavec offer a glimpse at some of the presentations guaranteed to spark one’s curiosity, spur debate, and enhance the field even further. Some key highlights include:

 Continued advancements in CAR T-cell therapy are expected to revolutionize the treatment of hematologic malignancies.

 Bispecific antibodies, such as Epcoritamab (Epkinly), offer a novel approach to target multiple antigens on cancer cells.

 The assessment of MRD is becoming increasingly important in predicting treatment response and overall survival.

Advances in Acute Lymphoblastic Leukemia (ALL)

Blinatumomab (Blincyto) in pediatric ALL:

 The addition of blinatumomab to chemotherapy has shown promise in improving disease-free survival in high-risk pediatric ALL. This combination therapy may offer a more effective treatment option for young patients.

Acalabrutinib (Calquence) in mantle cell lymphoma (MCL):

 The FDA is set to review the approval of acalabrutinib with bendamustine or rituximab (Rituxan) for previously untreated MCL, based on data from the phase 3 ECHO trial (NCT02972840).

Asciminib (Scemblix) in chronic phase chronic myelogenous leukemia (CML-CP):

 The FDA recently granted accelerated approval to asciminib for newly diagnosed CML-CP. This tyrosine kinase inhibitor has shown favorable safety and tolerability profiles.

 isn't just about data, as the duo also offers food recommendations, tourist attractions and fun activities to partake in, as well as interesting facts about San Diego.

This is just a taste of the wealth of information and inspiration waiting at the 2024 ASH Annual Meeting. Check back for future meeting previews with 

Targeted Oncology co-hosts Kristie L. Kahl and Andrew Svonavec highlight abstracts for community oncologists to look out for at the upcoming ASH Annual Meeting in San Diego, with some additional tidbits to round out the main event.

News

The biologics license application (BLA) of the subcutaneous formulation of nivolumab (Opdivo) coformulated with human hyaluronidase (rHuPH20) has been accepted by the FDA.

Findings from the CheckMate -67T (NCT04810078) support this BLA of subcutaneous nivolumab as the trial met its coprimary pharmacokinetic end points and key secondary end point of overall response rate (ORR) vs intravenous (IV) nivolumab in clear cell renal cell carcinoma.

The FDA has set a Prescription Drug User Fee Act (PDUFA) goal date for December 29, 2024.

The FDA has accepted the BLA of the subcutaneous formulation of nivolumab coformulated with rHuPH20, also known as subcutaneous nivolumab, for all previously approved adult solid tumor indications of nivolumab as a monotherapy, monotherapy maintenance following completion of the combination therapy with nivolumab plus ipilimumab (Yervoy), or in combination with chemotherapy or cabozantinib (Cabometyx).

Results from the phase 3 CheckMate -67T trial of subcutaneous nivolumab support this application. In the trial, experts sought to evaluate subcutaneous nivolumab vs its intravenous (IV) formulation.

 Here, the subcutaneous form demonstrated noninferior pharmacokinetics and efficacy, as well as consistent safety compared with the IV formulation of nivolumab among patients with advanced or metastatic clear cell renal cell carcinoma (ccRCC) who have received prior systemic therapy.

A PDUFA goal date has been set for December 29, 2024. With this, subcutaneous nivolumab shows promise to become the first and only subcutaneously administered PD-1 inhibitor.

“We believe subcutaneous nivolumab has the potential to make a significant difference in the lives of patients, which is reinforced by the FDA’s acceptance of our application,” said Gina Fusaro, PhD, vice president, global program lead, Bristol Myers Squibb, in a press release.

“[Nivolumab] is a foundational PD-1 inhibitor approved for many different types of cancer, and our continued investment in research that puts patients first remains a priority. If approved by the FDA, the subcutaneous administration of nivolumab would provide patients and their physicians with a new option that delivers the same well-known benefits as IV [nivolumab] but with the improved convenience of an injection administered in 3 to 5 minutes rather than a 30- to 60-minute infusion,” Fusaro continued.

The phase 3, randomized, open-label CheckMate -67T trial is exploring subcutaneous administration of nivolumab coformulated with rHuPH20 vs IV nivolumab for the treatment of patients with advanced or metastatic ccRCC who were previously treated with systemic therapy.

In the study, 495 patients were randomly assigned to receive either subcutaneous nivolumab or IV nivolumab. Enrollment was open to patients with a histological confirmation of ccRCC, advanced RCC not amenable to curative or radiation therapy, metastatic RCC, those who received no more than 2 prior systemic therapies, those with intolerance or progression after last treatment regimen within 6 months of randomization, and those with a Karnofsky performance score ≥ 70 at screening.

Experts assessed the coprimary end points of time-averaged serum concentration over 28 days and trough serum concentration at steady-state of subcutaneous nivolumab vs IV nivolumab. A key secondary end point of the trial was ORR.

The study met its coprimary pharmacokinetic end points and key secondary end point of ORR with subcutaneous nivolumab in this patient population.

 Subcutaneous nivolumab was noninferior in regard to time-averaged nivolumab serum concentration over 28 days and steady-state trough serum concentration vs treatment with IV nivolumab. Additionally, subcutaneous nivolumab also demonstrated a noninferior ORR compared with IV nivolumab.

1. U.S. Food and Drug Administration accepts Bristol Myers Squibb’s application for subcutaneous nivolumab (nivolumab and hyaluronidase). News release. Bristol Myers Squibb. May 6, 2024. Accessed May 6, 2024. 

2. Phase 3 Check-Mate -67T trial of subcutaneous nivolumab (nivolumab and hyaluranisade) meets co-primary end points in advanced or metastatic clear cell renal cell carcinoma. News release. Bristol Myers Squibb. October 19, 2024. Accessed May 6, 2024. 

3. A study of subcutaneous nivolumab versus intravenous nivolumab in participants with previously treated clear cell renal cell carcinoma that is advanced or has spread (CheckMate-67T). ClinicalTrials.gov. Updated October 12, 2023. Accessed May 6, 2024. 

https://www.clinicaltrials.gov/study/NCT04810078

The FDA is considering a subcutaneous nivolumab formulation for various solid tumors based on promising data from the phase 3 CheckMate -67T trial. A target action date has been set for December 29, 2024.

Clinical

FDA Accepts BLA for Subcutaneous Nivolumab Across Various Solid Tumors

70-year-old man with asymptomatic lymphocytosis identified 4 years previously​

Initially monitored; after 2 years, developed anemia, night sweats, and splenomegaly​

Treated with venetoclax (Venclexta) plus obinutuzumab​ (Gazyva)

CT of chest, abdomen, pelvis: largest node: 4.2 x 2.8 cm; all others less than 3 cm ​

High cardiovascular risk due to history of non-ST-elevation myocardial infarction status post 2 stents​

Simvastatin; amlodipine; clopidogrel, aspirin​

Fluorescence in situ hybridization: del(11q); w/o del(17p)​

What are your next steps for treatment of this patient with chronic lymphocytic leukemia (CLL)?​

If you look at the NCCN guidelines in the frontline setting, the recommended therapies are either a single-agent BTKI [Bruton tyrosine kinase inhibitor] continuously, or you can combine with an anti-CD20 [antibody] in the setting of acalabrutinib [Calquence], or venetoclax plus obinutuzumab, which is a fixed-duration treatment.

If you start with venetoclax plus obinutuzumab in the front line, it's a 1-year treatment. After the patient relapses, you can go to a BTKI, or you can repeat the venetoclax plus obinutuzumab [treatment]. You have both options. What is the duration of remission that would trigger you to re-treat with a venetoclax-based therapy? That’s subjective. There's no real guidance on what the minimum duration of remission is after you finish venetoclax plus obinutuzumab, but you have both options, venetoclax plus obinutuzumab or BTKI.

Would you re-treat with venetoclax plus obinutuzumab or venetoclax plus rituximab [Rituxan]? I use venetoclax plus obinutuzumab even in the relapse, because I think obinutuzumab is a better anti-CD20 than rituximab. What's the minimum duration of remission that triggers you to retreat?

Probably a year or more is what I have been using in this patient. Although with high risk, he has a couple years out of venetoclax plus obinutuzumab. He has some underlying cardiac issues. It may be better to consider venetoclax plus obinutuzumab again over BTKI, because of those toxicities.

Because you're worried about the risk of atrial fibrillation that comes with BTKI with this risk status. So, 1 year after [the end of] treatment, you would re-treat. There is no right or wrong. Two years might be good for somebody and might not be good enough for somebody else.

If it is already apparent that this was not a successful regimen, I would rather go to BTKI. It's continuous, and chances of relapse would be lower. I know it's not time bound, but I would probably go to zanubrutinib [Brukinsa], or pirtobrutinib [Jaypirca], or something like that.

Are you worried about the risk of bleeding with the dual anti-platelet [therapy]? Would you maybe talk to the cardiologist to see if you can take 1 off, and then monitor closely?

With acalabrutinib, it has been much lower, so we have successfully used it with cardiac patients. I have many patients like that. They are doing well.

Would you worry about atrial fibrillation in this patient, or just [the] bleeding, or both?

I would. But like I said, with venetoclax you could potentially rechallenge, but the patient has already shown that [CLL] has relapsed on the venetoclax-based regimen. I would try to do something else.

 So the 2-year treatment-free remission is not sufficient for you, and that's totally fair. I've seen [physicians who like] 2 years. I've seen [those who] would like to see 3 years. I've seen people like to see 4 years, or the whole median progression-free survival of 5 or 6 years.

Does a deletion 11q have anything to do with this? Don't they do better with BTKIs?

For a 11q, for some reason, if you give a BTKI to a patient with 11q, they seem to do somewhat better than the non-11q. I would say 11q is not a big player with BTKI. The 17p and complex karyotype might be a player in the relapsed setting. In the front line, none of this matters. Even if you have a 17p, they seem to do well in the long run, as if they don't have a 17p, as opposed to venetoclax plus obinutuzumab, where the high risk continues to play a role, particularly 

 mutation and complex karyotype, and then unmutated 

If the patient got a year or 2 out of that regime, I probably would put them on a BTKI. That doesn't mean that I'm done with venetoclax. Just because we don't use it now doesn't mean we may not use it down the road. He didn't relapse on it, and he had some degree of remission. I would not put him back on it immediately within 2 years, but I would keep it in reserve for the future when he needs another treatment switch.

These are 3 different strategies, and all 3 are being used, and none of them are wrong. It's a preference; it's experience. I agree, and you still have pirtobrutinib down the line if you progress on both.

If you choose to use a BTKI in the second line:​

How do you characterize the efficacy of acalabrutinib vs ibrutinib?​

How do you characterize the efficacy of zanubrutinib vs ibrutinib?​

Let's say you decide to go with a BTKI, which one do you go with? We’re going with covalent BTKI. We're keeping pirtobrutinib for later, at least for now. Are you doing ibrutinib [Imbruvica], acalabrutinib, or zanubrutinib?

I use acalabrutinib or zanubrutinib. I can tell you I use more acalabrutinib, maybe [this is] just a matter of habit, but that's what I will use for this patient. I know it is a preferred treatment by NCCN; ibrutinib is not a preferred treatment anymore. I think it is [as] effective as ibrutinib. It's probably less toxic there. It's a very reasonable option.

Between acalabrutinib and ibrutinib, which is superior in terms of efficacy?

What about zanubrutinib vs ibrutinib in terms of efficacy?

I think the ALPINE trial [NCT03734016] showed in the relapsed setting that zanubrutinib was better compared with ibrutinib.

You're on spot with that and both acalabrutinib and zanubrutinib were safer than ibrutinib.2,3

1. NCCN. Clinical Practice Guidelines in Oncology. Chronic lymphocytic leukemia/small lymphocytic leukemia, version 1.2025. Accessed January 20, 2025. 

https://www.nccn.org/professionals/physician_gls/pdf/cll.pdf

2. Brown JR, Eichhorst B, Lamanna N, et al. Sustained benefit of zanubrutinib vs ibrutinib in patients with R/R CLL/SLL: final comparative analysis of ALPINE. 

. 2024;144(26):2706-2717. doi:10.1182/blood.2024024667

3. Byrd JC, Hillmen P, Ghia P, et al. Acalabrutinib versus ibrutinib in previously treated chronic lymphocytic leukemia: results of the first randomized phase III trial. 

. 2021;39(31):3441-3452. doi:10.1200/JCO.21.01210

During a Case-Based Roundtable® event, Nakhle Saba, MD, and participants discussed treatment for a patient with chronic lymphocytic leukemia who received 1 prior line of therapy in the first article of a 2-part series. 

Deciding on Therapy for a Patient With High-Risk Relapsed CLL

ahnert-amy-1245260587.avif

Scientists and physicians have long been aware of links between cardiovascular disease (CVD) and breast cancer. Both conditions share common lifestyle risk factors, such as smoking, obesity, physical inactivity, and poor diet. Additionally, chemotherapy for breast cancer may increase the risk of developing chemotherapy-induced heart disease, known as cardiotoxicity.

For Heart Health Month, Amy Ahnert, MD, Director, Women’s Heart Program at Morristown Medical Center, Atlantic Health System, discussed the link between cardiovascular disease and breast cancer.


Mehmet Akce, MD

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