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Sabrina Serani is a senior editor for Targeted Oncology. 

Researchers presented updated results from longer-term follow-up studies of GC012F for newly-diagnosed multiple myeloma treatment at the International Myeloma Society Annual Meeting.  

GC012F CAR T Shows 100% Complete Response Rate in Multiple Myeloma 

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

A 77-year-old White woman presented to her primary care physician complaining of abdominal pain and fatigue.​ She had a history of cirrhosis due to heavy alcohol use; Crohn disease, controlled with infliximab [Avsola]; and a history of variceal bleeding, with banding 2 months ago​. Her ECOG performance status was 1​. A CT scan of her chest, abdomen, and pelvis with triphasic liver evaluation showed a 4.5-cm Liver Imaging Reporting and Data System 5 hepatic mass in the right lobe plus metastatic disease in the lung. She had a Child-Pugh score of A​ and an αfetoprotein level of 380 ng/mL. A biopsy was obtained and confirmed the diagnosis of hepatocellular carcinoma.

 I’d chose lenvatinib [Lenvima] because the patient [is receiving infliximab]. Otherwise, I probably would have used atezolizumab [Tecentriq] plus bevacizumab [Avastin].

 Anyone from the atezolizumab plus bevacizumab crowd? Why did you choose [that treatment]?

 I think it is the most preferred option. In this patient, there [was all that] plausible bleeding and Crohn disease, but it looks like everything is well controlled. The patient was banded recently and the risk of bleeding is lower, and it looks like the Crohn is well controlled too. It is not very clear, but I am assuming it is well controlled with infliximab. So the patient isn’t going to get a flare. One could use immunotherapy if they had colitis and didn’t respond to steroids, but you could use infliximab in those patients anyway. I feel like that patient is already on treatment and the autoimmune disorder is well controlled. If this patient doesn’t have a severe form of Crohn disease that is uncontrolled, immunotherapy is still an option.

How many of your patients are you treating if they have a history of autoimmune disease?

Are you comfortable treating those patients that have autoimmune disease that are potentially controlled?

 These are all questions that face us in the real-world practice because if you look at the trials of atezolizumab plus bevacizumab, they definitely excluded patients who had significant autoimmune diseases, or they had to have lower than physiologic doses of prednisone to be eligible for the study. So there were very fixed criteria for patients excluded from the trial. In real-world practice, how many people are using atezolizumab plus bevacizumab for patients with autoimmune conditions?

 Well controlled is when the specialist treating the patient says it’s well controlled. I am not a gastroenterologist, and I wouldn’t comment if somebody’s Crohn disease is well controlled, and the same with other autoimmune diseases. It should come from the subspecialists treating the patient. Also, symptom-wise, what kind of symptoms does the patient have? If they are symptomatic, obviously, they are not well controlled.

 I usually try to steer clear of immunotherapy when somebody is using an immunosuppressant if there is another option. I think there are active trials looking at these immunotherapies to see if they are acceptable in autoimmune diseases. Until we have more data, if there are other feasible options, I try to use them.

 I would say I am also conservative with this. In the IMbrave150 trial [NCT03434379] with atezolizumab plus bevacizumab, there were clearly defined exclusions. Our case is somewhat a high-risk patient because they are on an immune modulatory agent like infliximab that tells me, potentially, they were not able to be controlled by steroids. That is a little bit concerning for me. This is an ongoing area of research, particularly for patients with liver transplants on chronic immunosuppressants. Many of us wouldn’t necessarily treat them [with immune modulators] because early retrospective studies have shown high rejection rates. So I think it is very risky, but Dr. Chand I do understand your point about working with gastroenterology to make sure of what is defined as good control versus poor control. It’s a personal decision that is somewhat risky to [proceed with] because there can be significant toxicity when this is introduced in someone that is on immunosuppressants.

 What are your thoughts on bevacizumab? In which patients would you not use it? [With] portal hypertension that is systemic? How do you select it?

That is a very good question just because of the potential bleeding risk. In general, I would say I follow what was done in the trials. I do get endoscopy prior to starting treatment and I make sure that varices are treated. If someone has significant varices, particularly gastric varices that cannot be banded or eradicated and which traditionally have been very difficult to treat, I think that would potentially give me pause because those patients are at a very high risk for bleeding. Certainly, [I would not use bevacizumab] in someone who had an acute bleed prior to that. I would say that this in general applies for the tyrosine kinase inhibitors [TKIs] too.

In the National Comprehensive Cancer Network guidelines, atezolizumab plus bevacizumab is the preferred regimen for Child-Pugh A patients.

Other recommended regimens include sorafenib [Nexavar] and lenvatinib. Sorafenib includes Child-Pugh B7 patients and nivolumab [Opdivo] is useful in certain circumstances based off the CheckMate 459 study [NCT02576509] data for frontline therapy. Even though it wasn’t technically a positive study, it showed some benefit in terms of overall survival but not significant; however, FOLFOX is approved in China.

1. NCCN. Clinical Practice Guidelines in Oncology. Hepatobiliary cancers, version 1.2022. Accessed April 3, 2022. https://bit.ly/3Ao3MZW

During a live virtual event, Daneng Li, MD, discussed the case of a 77-year-old woman with stage IV hepatocellular cancer and a Child-Pugh score of A. 

This is the first of 2 articles from this event. 

Considering Treatment for Patients with HCC and Autoimmune Disease

A 59-year-old African-American woman presented with a left renal mass​. She underwent left radical nephrectomy in December 2019 revealing clear cell renal cell carcinoma (RCC)​. Nine months later, she developed nodules in both lungs, with mediastinal (35 × 38 mm), and retroperitoneal lymph nodes​. Lung biopsy confirmed stage IV RCC with clear-cell histology​. Her Karnofsky performance status was 90%​. Hemoglobin was 11.1 g/dL and ​corrected calcium, neutrophils, platelets were within normal limits. She was considered to have an International Metastatic RCC Database Consortium (IMDC) intermediate risk status.

: There is a higher rate of patients in the intermediate and poor [risk group] in the [CheckMate 214 trial; NCT02231749] of ipilimumab [Yervoy] plus nivolumab [Opdivo]. So even though the numbers look worse, I think that the population may be a bit different.

 If you look at the CLEAR trial [NCT02811861], the poor prognosis percentage is 9% against 17% in the [CheckMate 214 trial], so I [chose] ipilimumab/nivolumab.

 One of the other things that I take into consideration as a community oncologist is…how easy it is to give immunotherapy compared with adding a TKI [tyrosine kinase inhibitor] because the adverse events [AEs] are significant. Not always, but we need to do a lot of hand holding in terms of how we’re going to set the dose, and the timing of starting therapy because of pre-authorization process. I think that all the options are very valid, and I usually present all the options to the patients. But, in practicality, I like the idea of the ipilimumab/nivolumab and I’m more familiar with it, too.

 I think that’s a great point. First of all, when you look at [the 4 frontline trials,] there are different breakdowns for the different IMDC risk populations within the trial. Interestingly, the patients who have intermediate and poor risk tend to do better in these trials. I think that having a lower percentage of poor-risk patients is a disadvantage to that regimen because the favorable-risk patients do well almost regardless of what you give them. But I think the second point is accurate. All these regimens are 100% appropriate, but to choose one based on the ease of administration is completely reasonable.

I think we’ve been giving ipilimumab/nivolumab for the longest time of all these regimens because it was approved first. It has the longest follow-up, and when you look at the 5-year follow-up, approximately 50% of patients are still alive and approximately 30% are still progression-free.

 We’re comfortable giving it. It doesn’t require a TKI and [so] I give it as well.

 I voted for lenvatinib [Lenvima] and pembrolizumab [Keytruda]. The reason behind that is…patients like to see a little quicker response, so adding a TKI always give you a little quicker response than just IO [immunotherapy] plus IO. I have used all 4 regimens. I had a bad experience with axitinib [Inlyta] and pembrolizumab. The patient had a hypertensive crisis and was admitted to the hospital with seizures and delusions. We still do not know whether he had a posterior reversible encephalopathy versus just a hypertensive crisis. We had to discontinue axitinib and he is doing fine on pembrolizumab alone. Lately I've been using cabozantinib [Cabometyx] or lenvatinib/pembrolizumab, and I’m very comfortable with the combinations. I just have to do little dose adjustments. I’m in a community practice, so…I look at the risk factors but I’m not bound by the risk factors [for choosing which] combination I use. So far, I have not got pushback from the insurance companies. I have a few patients on lenvatinib/pembrolizumab and I’m very comfortable with that combination; they’re all doing very well.

 Great. It’s interesting to hear how much personal experience plays a role in decision making. If somebody has a bad experience with, let’s say, cabozantinib and nivolumab—in the context of having 3 other regimens approved, they’re not going back to it. So it’s interesting to hear that you have that experience with axitinib/pembrolizumab and you tried other regimens [and you were] comfortable with them.

 I’ve used axitinib/pembrolizumab and ipilimumab/nivolumab in this patient population, and both of these regimens have significant potential AEs. I have had patients on ipilimumab/nivolumab with significant AEs where I have to drop immunotherapy or at least 1 of the drugs, which made me a little bit reluctant to give it to patients whom I thought will do OK on axitinib and pembrolizumab. Having said that, I had patients with significant AEs with axitinib and had to either drop it or significantly dose reduce it. I use both of these regimens with caution, and the risk factors…but also clinical judgment is key. I use both of the regimens with excellent results and with patients who’ve had significant AEs.

 Is there a reason you would use axitinib/pembrolizumab over lenvatinib/pembrolizumab or cabozantinib/nivolumab or is it just you have the experience with axitinib/pembrolizumab?

 I definitely have much more experience with axitinib and pembrolizumab. For that very reason I don’t think I’ve ever use lenvatinib and pembrolizumab in metastatic RCC because I’m so much more familiar with the other regimens. I’ve used lenvatinib in other cancers and that can be a challenging drug, too.

 The lenvatinib/pembrolizumab looked like the best [drug] for progression-free survival, but…[the trial] had…very few patients with poor prognostic factors.

 I think comparing cross trial is not a good idea, in my opinion, because they do not have the same population enrolled. Personal experience is more important than this trial.

 I think the note that I would caution on is when you look at the subgroup analyses in these trials, the benefit is more significant in the patients who have intermediate and poor risk. So, one would expect that for a trial that has less than 10% of patients with poor risk, the outcomes would be a little bit worse than the other trials.

 I found lenvatinib the most difficult of these TKIs to manage out of all the TKIs that we have here. I have tended to use lenvatinib/pembrolizumab in patients who are very fit and very symptomatic since the objective response rate seems to be a bit higher.

 I have more experience with axitinib because at the Cleveland Clinic, we had the trial published by Brian Rini, MD, and we adopted it pretty fast.

 But, if somebody is at high cardiovascular risk, where TKIs would be very high risk, I have gone towards the IO/IO combination.

 Because we had a good chunk of patients on the trial and Dr Rini was here, we shifted to axitinib/pembrolizumab quickly when it got approved. And now there’s more of a smattering of different agents being used now that we have more approvals.

1. Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. 

2018;378(14):1277-1290. doi:10.1056/NEJMoa1712126


2. Motzer RJ, Tannir NM, McDermott DF, et al. Conditional survival and 5-year follow-up in CheckMate 214: First-line nivolumab + ipilimumab (N+I) versus sunitinib (S) in advanced renal cell carcinoma (aRCC).

2021;32(suppl_5):S678-S724. doi: 10.1016/annonc/annonc675

3. Motzer R, Alekseev B, Rha SY, et al; CLEAR Trial Investigators. Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. 

2021;384(14):1289-1300. doi:10.1056/NEJMoa2035716

4. Rini BI, Plimack ER, Stus V, et al. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. 

During a Targeted Oncology case-based roundtable event, Moshe Ornstein, MD, MA, discussed the factors influencing the choice of frontline therapy for a patient with stage IV clear cell renal cell carcinoma whose risk status was intermediate. 

Sabrina Serani

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