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Authors

Olalekan O Oluwole, MD, MBBS, is an associate professor, medicine, hematology/oncology, Vanderbilt Institute for Infection, Immunology and Inflammation, Vanderbilt University Medical Center.

Olalekan O Oluwole, MD, MBBS, discusses the background and rationale of the research he contributed to, which was presented at the 2025 Transplantation & Cellular Therapy Meetings.


Assessing the Need for Extended Monitoring After Axi-Cel Infusion

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 71-year-old man with a history of metastatic renal cell carcinoma (mRCC) had undergone a left nephrectomy and adrenalectomy. He had clear cell RCC (ccRCC) and metastases in his adrenal gland. Four years later, the patient had a recurrence of his cancer. A biopsy showed lung nodules consistent with ccRCC. In retrospect, it had been present on scans for at least 2 years prior.

The patient was observed based on the low volume and indolence of the disease and on his preference. Eighteen months later, a reexamination showed continued indolent growth on scans, with an increased total tumor burden, and a new paratracheal lymph node (20 × 15 mm). A decision was made to initiate systemic therapy with pembrolizumab (Keytruda) plus axitinib (Inlyta).

On follow-up, the patient’s disease had a confirmed partial response. The patient reported moderate diarrhea (well controlled with antidiarrheal medication) and mild fatigue. After cycle 6, he developed fatigue, mild shortness of breath, and mild cough without chest pain.

At approximately week 18, a chest CT scan confirmed grade 3 pneumonitis. Pembrolizumab treatment was held, and intravenous steroids were administered. Pembrolizumab then was discontinued, and the patient continued on axitinib.

Fourteen months after the initiation of systemic therapy, the patient reported increasing back pain, mild nausea, weight loss, and new onset of persistent rib pain. Imaging confirmed disease progression: the paratracheal lymph node had been 20 × 15 mm and was now 25 × 28 mm; there were new mediastinal and hilar nodal involvement, new retroperitoneal nodes, and new lytic lesions. He had an ECOG performance status of 1.

The patient was treated with 60 mg of cabozantinib (Cabometyx) once a day. Nine months later, disease progression was documented. The patient wanted to continue active therapy.

What are the goals of therapy going into the third line?

What factors most influence your choice of therapy?

When you get into the third-line setting of RCC, how do your priorities change? Are you still focused on progression-free survival [PFS] and overall survival, or are you thinking more about palliation?

: Typically palliation, but I have seen good results with tivozanib [Fotivda] and patients are living a while with it. I usually go with pembrolizumab plus axitinib first, then cabozantinib second. This way, I know I have a second option. If I use cabozantinib plus nivolumab [Opdivo], then I don’t know what to use as a second line. I have some problems with using tivozanib as second line from insurance. I have not seen that any one of the 3 [tyrosine kinase inhibitor (TKI) plus immunotherapy (IO) regimens] are better than the others with a big difference. With bone [metastatic] disease, I may use cabozantinib as a first line. That has been my approach for those patients. I’m one of the physicians who sees a lot of [patients with recurrent disease]; I have more than 5 [treated in the] second line, and probably 4 patients in the third line.

: In the community oncology setting, the patient population is little bit different than in the academic [setting]. Palliation is the No. 1 goal and close attention is given to the adverse event profile and tolerability. Depending on the patient population, the insurance also plays a role in terms of what they are going to be approved for, and what their out-of-pocket cost is going to be.

That makes perfect sense. I didn’t incorporate that financial element, but I definitely think that’s an important one.

Single-agent TKI (eg, sunitinib, pazopanib)

 [Approximately] 80% of participants chose tivozanib in this setting, with 13% choosing lenvatinib [Lenvima]/everolimus [Afinitor]. Dr Rapisuwon, what would you choose in this setting?

[I would choose] lenvatinib plus everolimus; we know, at least from our experience… often when we start people with IO/IO, and if IO doesn’t work, then we move on to cabozantinib. Cabozantinib would give a [progression-free interval] of maybe 9 to 12 months, then when a patient might progress on cabozantinib, they can still respond to lenvatinib/everolimus—although you just have to dose-reduce lenvatinib a lot.

I tend to have the same experience with lenvatinib and we’ll talk about some of the toxicity considerations around the drug.

Have you used tivozanib? If so, what are your impressions of it?

Dr Mattar, you had mentioned that you treated patients with tivozanib. Are [the data from TIVO-3 (NCT02627963)] fairly consistent with your experience with it?

Yes, I have a patient who is still responding. I’ve had a patient who started it and then had issues with infection, and went on dialysis, so I was anxious to keep it. I don’t know what your experience is using it in dialysis. I know the package insert does not define how to use it. But this patient is still doing well. It’s been 6 to 8 weeks now. I’m watching it, making sure that I’m seeing him more often. But my experience has been very good.

The challenge in dialysis is if we need to use [tivozanib], you use it. In clinical practice what I’ve done is started on a low dose in my patients on dialysis. I’ve started at 0.89 mg, see if they tolerate that, then I’ll escalate to 1.34 mg. It’s similar principle for [other] TKIs. I’ve occasionally started low and worked my way up very quickly, not waiting months to do this. I might increase the dose after a week or 2.

: Because they’re mostly hepatically metabolized, I’ve tended to treat [those patients] like I treat anybody else. It’s been a handful of patients, probably not even a dozen over the years, but I haven’t run into trouble. I haven’t found [dialysis] as limiting or dose modifying.

I’ve used [tivozanib] in the third-line setting. I have to say I’m very impressed. I have patients with relatively good PFS on the drug and tolerating very well. Going back to the conversation that we had before, in the third-line setting many of these patients have some decline in their performance status. I am very impressed at how they’re tolerating this TKI. It’s tempting to see more studies to see that drug in a frontline setting.

: I’ve been hearing about tivozanib for a long time. I’ve been in practice for 12 years and I remember hearing about it when I was a fellow. The thing that impresses me about it is that it is quite VEGF-receptor specific. We know from some other VEGF receptor–specific TKIs like axitinib that response rates are pretty low after a previous TKI exposure. But with tivozanib, we do see some meaningful responses after previous TKIs. I find it to be well tolerated. Generally, in the third line I will go with lenvatinib/everolimus, but I would have a conversation with the patient. I generally think lenvatinib/everolimus is more active and tivozanib is better tolerated.

I try to figure out what that patient’s particular goals are. But tivozanib has been well tolerated. Obviously, we run into hypertension, and we make dose adjustments and we’re very comfortable with it.

1. Rini BI, Pal SK, Escudier BJ, et al. Tivozanib versus sorafenib in patients with advanced renal cell carcinoma (TIVO-3): a phase 3, multicentre, randomised, controlled, open-label study. 

. 2020;21(1):95-104. doi:10.1016/S1470-2045(19)30735-1

2. Motzer RJ, Hutson TE, Glen H, et al. Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial. 

. 2015;16(15):1473-1482. doi:10.1016/S1470-2045(15)00290-9

During a Targeted Oncology™ Case-Based Roundtable™ event, Sumanta K. Pal, MD, discussed the case of an older patient with metastatic renal cell carcinoma who had recurrent disease after receiving axitinib and pembrolizumb, then single-agent cabozantinib. This is the first of 2 articles based on this event. 

Peers Discuss Impressions of Tivozanib’s Role as Third-Line RCC Therapy

A 68-year-old woman presented to her physician with symptoms of fatigue and abdominal pain lasting 4 months; she also reported increased bruising​.

Spleen was palpable 8 cm below the left costal margin​.

Bone marrow biopsy: megakaryocyte proliferation and atypia with evidence of reticulin fibrosis​

Blood smear reveals leukoerythroblastosis

Initiate ruxolitinib ± refer for stem cell transplant

Initiate fedratinib ± refer for stem cell transplant

: How would you approach treating this patient with Janus kinase (JAK) inhibitors and a stem cell transplant?

 First, I think the decision for [allogeneic hematopoietic stem cell] transplant is a complex one. I take a generous view of having the transplanters visit with everyone who might be a transplant candidate, either now or in the near future. Second, I’ve found that patients can be quite variable, particularly in their late 60s or 70s, as to whether they want to go through with a transplant. It’s not uncommon for me to see patients that are recommended to have a transplant who decline it, given the complexity that can go with that. Almost all patients are on a JAK inhibitor or have had a JAK inhibitor.

One thing I think we’ve learned over time is that you clearly can be on a JAK inhibitor and then go to transplant, which was questioned at first. Probably the best time to go for transplant is when you’re having your best response to the JAK inhibitor. What we’ve found is that the outcomes are probably worse for transplant as a salvage therapy for the patient who has failed multiple JAK inhibitors. The outcomes are probably best before the patient [wants] transplant. The spleen is smaller, their performance status is better. They probably do better in engraftment; it does make it challenging, but that is probably when they do best.

How do the National Comprehensive Cancer Network (NCCN) guidelines advise treating patients with higher-risk myelofibrosis?

In terms of the NCCN guidelines, as we look at patients with higher-risk disease—which are probably the majority—at this point, we still stratify patients based on their platelet count.

 We have 2 approved agents: ruxolitinib [Jakafi] and fedratinib [Inrebic], and both are FDA approved for platelet counts over 50,000 (50 × 10

During a live virtual event, Ruben Mesa, MD, discussed the use and sequencing of JAK inhibitors and stem cell transplant for patients with myelofibrosis. 

Olalekan O Oluwole, MD, MBBS

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