BRAIN CANCER

HER2 Breast Cancer

BREAST CANCER

Bladder Cancer

Prostate Cancer

Renal Cell Carcinoma

GENITOURINARY CANCERS

Liquid Biopsies

GENOMIC TESTING

Colorectal Cancer

GIST

Gastric Cancer

GI CANCERS

Cervical Cancer

Endometrial Cancer

Ovarian Cancer

GYNECOLOGIC CANCERS

HEAD & NECK CANCERS

Bone Marrow & Stem Cell Transplant

HEMATOLOGY

CAR T-Cell Therapy

IMMUNOTHERAPY

Chronic Lymphocytic Leukemia

Chronic Myeloid Leukemia

LEUKEMIAS

Biomarker-Driven Lung Cancer

EGFR+ Lung Cancer

MET-Targeted Therapy

Small Cell Lung Cancer

LUNG CANCER

DLBCL

Follicular Lymphoma

Mantle Cell Lymphoma

LYMPHOMAS

MPNs

MULTIPLE MYELOMA

NTRK GENE FUSIONS

SARCOMA

Melanoma

SKIN CANCERS

THYROID CANCERS

NEWS

Special Reports

All News

FDA Briefs

Oncology Icons

The Targeted Pulse

Voices from the Field

CONFERENCES

Conference Coverage

Conference Listing

Data Dialogue with the Oncology Brothers

MEDIA

All Videos

Case-Based Peer Perspectives

Evolving Paradigms in Oncology

Expert Perspective Virtual Tumor Board

Interviews

Investigator Perspectives

Medical World News

Personalized Medicine

Pivotal Practice Views with the Oncology Brothers

Podcasts

Speaking Out

PUBLICATIONS

All Publications

Evolving Paradigms

Peers & Perspectives in Oncology

Targeted Therapies in Oncology

CASE-BASED ROUNDTABLE

PARTNERS

RESOURCES

CME/CE

Clinical Trials

Events

Precision Medicine Perspectives

Press Releases

Treatment Resources

SUBSCRIBE

Targeted Oncology provides news, videos, and reviews on the rapidly evolving world of targeted therapies and immunotherapy for oncologists treating patients in a community setting.

About Us

Advertise

Contact Us

CureToday.com

CancerNetwork.com

OncLive.com

OncNursingNews.com

Do Not Sell My Information

Privacy

Terms & Conditions

Editorial Board

Targeted Oncology - Immunotherapy, Biomarkers, and Cancer Pathways

Facebook

Linkedin

YouTube

Instagram

Featured Clinical Focus

BTK Inhibitors: In-Focus

Bone Marrow & SCT

EGFR-Positive Lung Cancer

Lung Cancer

Multiple Myeloma

Thyroid Cancers

Clinical Focus

Brain Cancer

Breast Cancer

Gastrointestinal Cancer

Genitourinary Cancers

Gynecologic Cancers

Head & Neck Cancers

Hematology

Leukemias

Lymphomas

Sarcoma

Skin Cancers

Spotlight

1rem

Authors

Primary liver cancer death rates vary by region, and much is still to be done in the area of health equity. 

Achieving Health Equity in Liver Cancer

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 68-year-old woman presented to her physician with symptoms of mild fatigue. Spleen was palpable 6 to 7 cm below the left costal margin​. She had no known comorbidities​. Next-generation sequencing showed a 

 V617F mutation​. Bone marrow biopsy showed megakaryocyte proliferation and atypia with evidence of reticulin fibrosis​; blood smear revealed leukoerythroblastosis​. She received a diagnosis of primary myelofibrosis​ with Dynamic International Prognostic Scoring System intermediate-1​ risk. Laboratory values included hemoglobin of 9.7 g/dL, hematocrit 32.3%, and platelet count of 450,000/μL.

In your experience with myelofibrosis, which symptoms/presentations have the most negative impact on patients’ quality of life?​

[Symptoms with negative impact include] early satiety, fatigue, night sweats, bone pain, mood changes and minor attention problems, neurocognitive symptoms, but the main things are the [enlarged] spleen, anemia, and if they bleed from the thrombocytopenia. If they have a 

 [mutation], it can cause clots in the mesenteric vein or in the portal system.

Dr Lekakis covered a lot of ground there…. He also talked about neurocognitive or neuropsychiatric symptoms that are probably underappreciated in these patients, and some of the thrombotic issues as well. You can see a variety of symptoms that are impacting quality of life.

What is the trigger to initiate therapy?​

How important is it to initiate therapy early?​

I usually get started at diagnosis. Most of my patients are somewhat symptomatic with these very nonspecific symptoms, so I start ruxolitinib [Jakafi] right away.

What have you noticed that improves the most in these patients with ruxolitinib?

In my experience, the splenomegaly is what improves the most.

Dr Madadi, what's the trigger for you to start either ruxolitinib or another JAK inhibitor?

I use the NCCN criteria; splenomegaly, fatigue, pruritus, or worsening cytopenias would be indications for starting treatment. But now, with the overall survival [benefit shown for ruxolitinib,

 because] the majority of the patients have some of the other symptoms, we start with ruxolitinib unless there is significant anemia or other cytopenias.

That's fair. Does anyone have patients for whom you wait to start a JAK inhibitor until the symptoms are more prominent?

Especially with anemia and with fatigue, I feel starting early is better.

I have some patients for whom I didn't start therapy for many years, who sometimes go beyond the usual natural course of the disease. But eventually, all of them come for treatment. There are asymptomatic patients who have minimal symptoms, or they have a little bit of fatigue or a little bit of discomfort from the spleen. There are those patients who don't want to get treated, who hear the possible adverse events and say, “I will wait.” On the other hand, there have been some studies that show that there is probably some modification of the natural history of the disease; it’s modest, but there is something.

It’s easy to think of a reflex to start all these patients on therapy, but then sometimes the patients read about the potential adverse events of these agents, and they come back [saying] "I don't know if I necessarily want to go on these things," and the data for disease modification are pretty weak. There are some studies that suggest there is some disease modification, but largely, these are agents that help with symptoms. It is more of a nuanced discussion.

When do you consider clinical trial enrollment?

Are you thinking about clinical trials upfront, or is that something that is evaluated when sending a patient for a transplant evaluation, or after refractory disease?

I work in the Levine Cancer Institute, so I tend to send most of my patients to see the leukemia and myeloproliferative [specialists], especially if they're intermediate or high risk. They already get assessed if there's a clinical trial, but they also have that conversation about transplant down the line before I even start anything.

So you're sending these patients upfront at diagnosis.

Most of them; there are some who don't want to [get a consultation].

Most of my patients are older, and I'm 90 minutes from an academic center that does transplant. It becomes challenging [to enroll in] a clinical trial as well. We do start JAK inhibitors here.

Initiate ruxolitinib ± refer for stem cell transplant

Initiate momelotinib ± refer for stem cell transplant

Initiate pacritinib ± refer for stem cell transplant

 Most are saying to initiate ruxolitinib plus or minus referral for stem cell transplant. One responder said to just refer for stem cell transplant at this point in time. I would agree that’s probably my approach for this patient who has mild anemia, intact platelet counts, splenomegaly, constitutional symptoms, and seems like a good candidate for frontline ruxolitinib therapy. I would refer this patient for transplant to meet [the transplant physician], even though they have intermediate-1 risk. Transplant might not be something on the table right now, but sometimes that discussion is good to have earlier, rather than later.

Referring to the same patient, now we've changed the hemoglobin. Instead of 9.7 g/dL, our hemoglobin here is 7.8 g/dL. All other aspects of the case are the same. Would this alternate scenario change your approach for this patient?

We've got a little bit of an even split saying yes vs no. How would this have changed your approach?

Momelotinib [Ojjaara] and pacritinib [Vonjo] give less anemia than ruxolitinib. Ruxolitinib, if you go with full dose, usually drops the hemoglobin by 1.5 g/dL. But with momelotinib or pacritinib, you may see the hemoglobin even go up a little.

So with the anemia you don't want to drop her into the 6 g/dL range and have to start dealing with transfusions right off the bat. Let's see if we can get the same benefit, but also maintain that hemoglobin, maybe even improve it a little bit.

I would say [something] similar, that momelotinib helps with the anemia. Especially with severe anemia, it would be more helpful.

I might just start out a lower dose of ruxolitinib and still try to treat the splenomegaly. I can see myself using momelotinib, but I would just probably just start at a lower dose of ruxolitinib.

So give it a try and see what ruxolitinib does. We have a lot of experience with ruxolitinib. Let's see how the hemoglobin responds, and then, if we need to, maybe momelotinib is the backup plan. Does age or frailty factor into this at all? Is that a consideration when you're [treating] this patient? Does the patient being aged 68 factor into your decision-making?

With frailty, if the symptoms are from the disease, I still try the medications. If symptoms are otherwise, if they have multiple comorbidities—I have a patient with Parkinson disease, and they have a lot of symptoms from the Parkinson disease and frailty. Then I'm thinking of what kind of medication I give him and what dose? Frailty does affect the treatment management.

1. Harrison CN, Vannucchi AM, Kiladjian JJ, et al. Long-term findings from COMFORT-II, a phase 3 study of ruxolitinib vs best available therapy for myelofibrosis. 

. 2016;30(8):1701-1707. doi:10.1038/leu.2016.148

2. Deininger M, Radich J, Burn TC, Huber R, Paranagama D, Verstovsek S. The effect of long-term ruxolitinib treatment on JAK2p.V617F allele burden in patients with myelofibrosis. 

. 2015;126(13):1551-1554. doi:10.1182/blood-2015-03-635235

During a Case-Based Roundtable® event, Andrew Kuykendall, MD, and participants discussed the the importance of early intervention and consideration of anemia with JAK inhibitor therapy for patients with myelofibrosis in the first article of a 2-part series.

Lewis R. Roberts, PhD, MB, ChB

Articles

Latest Updated Articles