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Authors

Firas Eladoumikdachi, MD, FACS, is a breast surgical oncologist, associate professor of surgery, Rutgers Robert Wood Johnson Medical School.

Firas Eladoumikdachi, MD, FACS, and M. Michele Blackwood, MD, FACS, assess preoperative radiation boosts in breast cancer care.

Breast Cancer Study Shows Minimal Score Variation After Radiation Boost

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

Durvalumab (Imfinzi) has been approved by the FDA for the treatment of patients with muscle-invasive bladder cancer (MIBC).

Positive data from the phase 3 NIAGARA trial (NCT03732677) support this approval.

In the study, durvalumab led to statistically significant and clinically meaningful improvements in event-free survival (EFS) and overall survival (OS) in this patient population.

The FDA has approved durvalumab plus chemotherapy followed by single-agent durvalumab for the treatment of patients with MIBC after radical cystectomy, based on findings from the phase 3 NIAGARA trial.

According to data from the randomized, open-label, multicenter, global NIAGARA trial 

presented during the 2024 European Society for Medical Oncology (ESMO) Congress

 neoadjuvant durvalumab given with chemotherapy, followed by adjuvant durvalumab, significantly improved EFS and OS in patients with cisplatin-eligible MIBC vs neoadjuvant chemotherapy plus placebo. These benefits were achieved without affecting patients' ability to undergo radical cystectomy.

This approval of durvalumab for patients with MIBC marks the first and only perioperative immunotherapy regimen available for this patient population.

The NIAGARA trial included adult patients with cisplatin-eligible MIBC with a clinical stage of T2-T4aN0/1M0.2 A total of 1530 patients were enrolled in the study, and 1063 patients were randomly assigned in a 1:1 fashion to receive 1500 mg of intravenous durvalumab every 3 weeks plus gemcitabine/cisplatin for 4 cycles, followed by durvalumab alone every 4 weeks post-radical cystectomy for 8 cycles; or 4 cycles of gemcitabine/cisplatin alone prior to cystectomy, followed by no further treatment after surgery.

The primary end points of the trial were EFS by blinded independent review and pCR rate at the time of cystectomy. Secondary end points included OS and safety, and additional end points were disease-free survival, disease-specific survival, metastasis-free survival, health-related quality of life, and 5-year OS.

Findings from the planned interim analysis showed that perioperative durvalumab led to a 32% reduction in the risk of disease progression, recurrence, not undergoing surgery, or death compared with neoadjuvant chemotherapy with radical cystectomy alone (95% CI, 0.56-0.82; 

<.0001). Among those treated with durvalumab, the estimated median EFS was not yet reached vs 46.1 months in the comparator arm. At 2 years, an estimated 67.8% of patients in the durvalumab arm vs 59.8% in the comparator arm were event-free.



Looking at OS, treatment with the durvalumab perioperative regimen reduced the risk of death by 25% vs neoadjuvant chemotherapy with radical cystectomy (HR, 0.75; 95% CI, 0.59-0.93; 

 =.0106). In both arms, the median survival was not yet reached. At 2 years, an estimated 82.2% of patients given the durvalumab regimen and 75.2% in the comparator arm were alive.

The durvalumab regimen was also generally well tolerated with no new safety signals seen in both the neoadjuvant and adjuvant settings. In both arms, the majority of patients had adverse events (AEs) of any cause (99% in the durvalumab arm; 100% in the comparator arm), 69% and 68% of which were grade 3/4, respectively.

Serious AEs were observed in 62% of patients receiving durvalumab and 55% in the comparator arm. Reported AEs included those leading to death (5% vs. 6%), treatment discontinuation (21% vs. 15%), discontinuation of neoadjuvant durvalumab (9%; NA), discontinuation of neoadjuvant chemotherapy (14% vs. 15%), failure to undergo radical cystectomy (1% in both groups), surgical delays (2% vs. 1%), and discontinuation of adjuvant durvalumab (8%; NA).

Additionally, 41% of patients in both arms had potential treatment-related AEs, 0.6% of which resulted in death in both arms. Any-grade immune-mediated AEs were seen in 21% and 3% of patients in the durvalumab arm vs the comparator arm.

FDA approves durvalumab for muscle invasive bladder cancer. News release. FDA. March 28, 2025. Accessed March 28, 2025. https://tinyurl.com/yc57uhb3

Powles T, Van der Heijden MS, Galsky M, et al. A randomized phase III trial of neoadjuvant durvalumab plus chemotherapy followed by radical cystectomy and adjuvant durvalumab in muscle-invasive bladder cancer (NIAGARA). Presented at: 2024 ESMO Congress; September 13-17, 2024; Barcelona, Spain. Abstract LBA5.

This approval of durvalumab marks the first and only perioperative immunotherapy regimen available in muscle-invasive bladder cancer.


FDA Grants Approval to Durvalumab in MIBC

Ongoing studies of Ra- 223–based combinations

What are some other ongoing investigations looking at Ra-223-based combinations?

An expert discusses other ongoing investigations exploring radium-223-based combinations for the treatment of metastatic castration-resistant prostate cancer, highlighting key studies and their potential impact on clinical practice.

Case Based Peer Perspectives

Video Series

How do you monitor and manage anemia in patients with primary myelofibrosis prior to starting Janus kinase (JAK) inhibitor therapy?​

How do you monitor and manage anemia in patients with myelofibrosis even prior to starting a JAK inhibitor? If you're initially evaluating someone, they come in with hemoglobin of 7 or 8 g/dL or something like that, how does that impact your thinking, and how do you work that up?

The first thing is to make sure that they don't have something easily fixable [such as] iron, B12, or folate deficiency. Theoretically, if you don't have any nutritional cause or any immune causes, you could use erythropoietin analogs, but they are very tricky because they don't help with the spleen, at least in my experience, and they may increase the risk of clots. I try to avoid them if possible. If I have to start a JAK inhibitor, if they have symptoms, either I go away from ruxolitinib [Jakafi] or I start a low dose of ruxolitinib. Sometimes I use anabolic steroids and prednisone. We have the thalidomide/prednisone [regimen] that now is kind of forgotten about.

Erythropoietin-stimulating agents [ESAs] are limited in what they do, and certainly not helping other aspects of the disease. You did mention one of my favorite regimens, thalidomide/prednisone, which is looked over a bit nowadays, but has quite a potential for efficacy in terms of improving hemoglobin. But it’s probably something that's gone by the wayside in many practices.

As Dr Lekakis says, there are some other options that you can use. Danazol is sometimes something you can use perfectly in this patient population. From the JAK inhibitors, there is momelotinib [Ojjaara]. But a priority for me is to refer a patient for a stem cell transplant; when I was a fellow, we did the first allogeneic bone marrow transplant at the University of Illinois, Chicago, and it was a very nice experience.

Dr Lekakis] also mentioned steroids, [and we are] thinking about things like danazol, androgen derivatives. We saw from the MOMENTUM study [NCT04173494] looking at momelotinib that danazol is an active agent.

 It was a large, randomized trial, one of the first randomized trials with danazol. The focus there was on momelotinib, but there's also a lot to learn about what danazol could do as well from that study.

You're mainly talking about anemia here, and [if], the patient is not a candidate for a transplant or a clinical trial [there are] the 

, which basically double the response and reduction of the spleen.

Yes, these emerging therapies to some degree may change how we approach this disease. But I think that with some of these older therapies, especially when you're when you're first talking about someone who's coming in with anemia, you need to think about ESA, danazol, and thalidomide/prednisone.

I think that ESA is probably the most prominently used. How many of you are checking serum erythropoietin levels in these patients to assess their candidacy for ESAs, is that a common practice?

Now in terms of the patient who develops anemia while receiving a JAK inhibitor, ruxolitinib or fedratinib [Inrebic], how do you then approach that patient? This is the someone on therapy who may not have had prominent anemia before, but now that anemia is a little bit more obvious.

I would reduce the dose. I cannot stop [ruxolitinib] easily because of the withdrawal symptoms, but I would reduce the dose.

I probably would be giving a lower dose or initiating at a lower dose if they are anemic, and then I can go up later if I have to.

With the option of reducing dose, and now newer JAK inhibitors that are available, how do you decide between changing therapy vs reducing the dose of ruxolitinib?

I would try to maximize the use of ruxolitinib and then go to the next drug.

During a live event, Andrew Kuykendall, MD, discussed management of anemia before and during use of JAK inhibitor for myelofibrosis in the second of 2 articles. 

Firas Eladoumikdachi, MD, FACS

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