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Panelists discuss how the initial presentation of lower-risk myelodysplastic syndromes (LR-MDS) involves anemia and other cytopenias, with updates on MDS risk assessment using prognostic scoring systems like such as IPSS-R and IPSS-M to guide treatment decisions.

Defining LR-MDS: Initial Patient Presentation and Updates in MDS Risk.

Following a recent update in to NCCN gGuidelines, Drs. Garcia- Manero and Swoboda introduce themselves and theirwill discussion about the changing landscape of lower-risk myelodysplastic syndromeLR-MDS treatment.

Introduction to the Discussion of Frontline Treatment for Newly Diagnosed Lower-Risk Myelodysplastic Syndromes.

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 60-year-old White woman was diagnosed with stage II multiple myeloma. She has a history of being a heavy smoker, with a gain (1q21) cytogenetics and an ECOG performance score of 0. At the time, she was treated with bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (VRd) induction therapy, followed by autologous stem cell transplantation (ASCT). She achieved a complete remission with VRd and ASCT, and was minimal residual disease negative, then placed on lenalidomide maintenance therapy.

At a follow-up after 2 years on lenalidomide maintenance, the patient reported having severe fatigue and pain in her back and legs, which disrupted her ability to continue working full time. A PET scan showed vertebral fracture at L1, lesions in both femurs, and an ECOG performance score of 1. Her current lab levels were the following:

M protein, 1.98 g/dL (rapid increase from prior bloodwork)

λ free light chain increased from 47.5 mg/dL to 136.7 mg/dL

White blood cell counts and platelets: within normal limits

Creatinine: 1.4 mg/dL (range, 0.59-1.04 mg/dL)

Daratumumab, carfilzomib, and dexamethasone

Isatuximab, carfilzomib, and dexamethasone

Daratumumab, pomalidomide, and dexamethasone

Isatuximab, pomalidomide, and dexamethasone

Daratumumab, bortezomib, and dexamethasone

Pomalidomide, bortezomib, and dexamethasone

 Does anyone want to comment why you’re using dara-Kd [daratumumab (Darzalex), carfilzomib (Kyprolis), and dexamethasone], isa-Kd [isatuximab (Sarclisa), carfilzomib, and dexamethasone], or [one of the other regimens]?

 We’re more familiar with daratumumab. None of those answers would be wrong. Because the patient relapsed after 2 or 3 years, even bortezomib would be reasonable to [reuse]. It’s important to introduce anti-CD38 therapy now because the patient wasn’t treated with that. But any of those combinations are OK. I swayed towards carfilzomib because the patient progressed on lenalidomide and I would think the patient would benefit from switching the mechanism from IMiD [immunomodulatory drug] to proteasome inhibitor. But I think even the regimen with pomalidomide [Pomalyst] would be very reasonable.

 Is there any reason why somebody would choose dara-Pd [daratumumab/pomalidomide/dexamethasone]?

 I have used dara-Pd as second-line therapy. It’s [our practice’s] most used regimen for second-line therapy. I agree with Dr Barsouk that introducing anti-CD38 is important in the selection of treatment of relapsed second-line therapy after transplant. Pomalidomide is not lenalidomide; they are not interchangeable, so I think we see efficacy with pomalidomide after lenalidomide progression.

 Yes, I agree. I also choose dara-Kd. Dara-Pd also would be appropriate. If the patient has any cardiac history, daratumumab, bortezomib, and dexamethasone, for instance, is an absolutely inappropriate regimen. As you all pointed out, an anti-CD38 antibody is important at that point.

Would you use a monoclonal antibody at first relapse or hold for a later line of therapy for those who haven’t seen one yet? If yes, which do you use? ​

What backbone partner would you choose for this patient with aggressive early relapse on lenalidomide maintenance?

Please discuss the patient-, disease-, and therapy-related factors you consider when choosing second-line therapy for a patient like this with aggressive early relapse on lenalidomide maintenance.

 Would you use a monoclonal antibody at first relapse or do you hold it for later line of therapy for those patients who haven’t seen a CD38 monoclonal antibody? Do you keep it because you might treat the patient with VRd, then switch to KPd [carfilzomib, pomalidomide, and dexamethasone] and leave the CD38 monoclonal antibody for the next relapse? Or do you think the patient needs to be treated at that point?

 At first relapse, I always use a CD38 monoclonal antibody if they haven’t already been on it in the past.

 I also agree with this. I would use one CD38 antibody or another. Historically, we’ve been more and more familiar with daratumumab, but isatuximab is also coming into play. In terms of choice between pomalidomide and carfilzomib, comorbidities play a role but so do the patient’s convenience and the quality of life. If [a patient] wants to be on a mostly oral regimen, only coming to the office every 2 weeks and then once a month for daratumumab, then for carfilzomib, the regimen is a little bit more tedious. But we use that as well.

 Are you using twice weekly carfilzomib or once a week?

 We use twice weekly because this is for a patient who has relapsed and you want to give them the best option, especially if it’s a young patient. For somebody older, then maybe we’ll do once a week. But we’re trying to stick to a standard schedule. What would you recommend?

 I use it for patient convenience and our infusion center is [short on] infusion chairs. I use it once a week and I go up to 56 mg/m

 We are as well. Everybody is getting the carfilzomib once a week, and at the 56 mg/m

 dose. In a few patients who tolerate well, I try to give 70 mg/m

 once a week. When they stabilized, there are 2 or 3 patients whom I started to give isatuximab, and the isatuximab is every 2 weeks. After a while I try also to give the carfilzomib if they are stable and have a very good response, together with the [isatuximab] twice a month, so they come in every 2 weeks.

 I use an antibody for the first relapse. I would not reserve this for later because you want to get a good drug in the front so the patient can get a deep response and go on to transplant. Regarding choice of the backbone, whether proteasome inhibitor or IMiDs, I agree. I want to see when the patient relapsed on the lenalidomide. I was in more favor of a proteasome inhibitor but I am also looking at the patient’s comorbidities to help to make a drug choice.

 What is the strongest factor that makes you use a different backbone? For instance, we say a CD38 monoclonal antibody is important. But what influences your decision whether you use pomalidomide over carfilzomib?

 I think every patient is different. [Data show] that triplet therapy in relapsed/refractory disease is much better than doublet therapy. In the studies, there was not a lot of information about cytogenetics, and which agent is effective. For example, we know that with 1q21 abnormalities, isatuximab may be more effective than others.

 But I cannot delineate which one is better. Daratumumab [can be given] subcutaneously, and hopefully, isatuximab, when it comes out subcutaneously might also be appealing. Carfilzomib once a week at 70 mg/m2, and later on when they have good response, every other week. I have that done many times. But the idea is that triplet is better than doublet.

 I agree. There is a majority that [believes] at this point the patient should have received a CD38 monoclonal antibody, at least in the first line. I would not keep it for a later line because it’s important that you induce the deepest remission up front that lasts for a longer time.

The patient was started on Isa-Kd and achieved a very good partial response.

 What is your experience and why did you do this?

 The first patient I used it in, [it was] because he didn’t like the subcutaneous daratumumab and he was willing to get an intravenous infusion. Since I see that it’s quite effective and if the patient has an infusion port already, it’s not a problem to administer. I saw that the results are really good. It’s a very effective regimen, so I started to use it.

 I have used this regimen, however in third-line therapy after progression on daratumumab. I found that isatuximab is not [the same as] daratumumab. These are different agents, so I have good success; patients who are progressing or not responding to daratumumab respond to isa-Kd.

 OK, interesting. Has anybody combined isatuximab with other partners, with pomalidomide, for instance?

1. Martin T, Richardson PG, Facon T, et al. Primary outcomes by 1q21+ status for isatuximab-treated patients with relapsed/refractory multiple myeloma: subgroup analyses from ICARIA-MM and IKEMA. 

. 2022;107(10):2485-2491. doi:10.3324/haematol.2022.280660

2. Moreau P, Dimopoulos MA, Mikhael J, et al. Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial. 

. 2021;397(10292):2361-2371. doi:10.1016/S0140-6736(21)00592-4

During a Targeted Oncology™ Case-Based Roundtable™ event, Suzanne Lentzsch, MD, PhD, discussed with participants their choice of combination therapy after disease relapse of multiple myeloma. 

David Swoboda, MD

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