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Adding E-602 to cemiplimab demonstrated anti-tumor effects in patients PD-L1–resistant solid cancers. 

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Heather Greene, MSN, FNP, AOCNP, shares insight into the use of erdafitinib in patients with locally advanced or metastatic urothelial carcinoma.

RX Road Map: Erdafitinib (Balversa)

Caroline Seymour joined MJH Life Sciences in 2018 and has expertise in video production and print/digital publication. Email: cseymour@onclive.com​

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Patients treated with ide-cel, Abecma for relapsed/refractory multiple myeloma affecting the central nervous system had similar outcomes to matched patients with non-CNS multiple myeloma.

Real-World Use of Ide-cel Provides Favorable Outcomes in CNS Myeloma

Amanda Brink is a nurse practitioner at the University of Texas MD Anderson Cancer Center. When she is not tending to patients in the hospital or clinic, she finds great satisfaction in crafting content to enlighten the public and her fellow nurses about a range of health topics.

Oncology nurses can educate patients on the implications of these findings

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“We've had to develop a unique process and a unique cryo buffer that allows us to freeze natural killer cells and recover greater than 90% of those cells. So, the new GDA-201 cryo-preserved is now going to be an off-the-shelf product and we're going to reinstitute a multicenter study in lymphoma to include both histologies of follicular lymphoma and diffuse large B cell lymphoma.”

Addressing Production and Logistic Challenges in Cell Therapy 

“So, what we’ve done is develop a technique, using the NAM technology, to expand those stem cells, so we can make 50 to 100-fold more stem cells, with higher reliability, and manufacture those cells for patients in need of a bone marrow transplant”

Omidubicel May Be a Potential Alternative to Bone Marrow Transplant

While high-risk multiple myeloma can be difficult to treat with aggressive therapies, treatment considerations with the help of diagnostic tools may prove helpful when determining when to de-escalate treatment for certain patients.

At a recent Community Case Forum hosted by Oncology Nursing News, Mark Davis, PA-C, a physician assistant from Texas Oncology, Southwest Forth Worth Cancer Center, and colleagues discussed disease burden and diagnostic tools, as well as risk stratification and treatment approaches in high-risk multiple myeloma.

“In terms of risk stratification, we use the International Staging System [ISS], which is more or less the old way of doing it…” Davis explained during the event, adding that providers use the revised ISS with lactate dehydrogenase (LDH) levels and high-risk cytogenetics of chromosomal abnormalities. “So somebody who has a double-hit myeloma, that means they have 2 chromosomal abnormalities, and that is going to put them at a higher risk classification.”

Factors associated with high-risk disease or the progressive relapse setting include those with newly diagnosed myeloma who have a revised ISS of III, extramedullary disease, circulating plasma cells, and cytogenic abnormalities. For patients with newly diagnosed multiple myeloma, cytogenic abnormalities associated with high risk for disease progression or relapse include Del(1p32), t(4;14), t(14;16), t(14;20), Del(17p) or monosomy 

 mutation, 1q21 gain or amplification, and MYC translocation.

“As an [advanced practice provider (APP)] we can really help clinicians not only identify high-risk patients based on cytogenetics but also those who have a short course of remission and identify them as high risk as well,” Davis said in an interview with Oncology Nursing News. “And so patients who have disease progression within 2 years of their induction therapy, [that] automatically puts them in a subgroup of high-risk disease. And we are trying to tailor therapies differently in those patient populations that have more aggressive disease.”

Factors that may impact treatment for patients include their personal preferences, physical activity, work productivity, comorbidities, quality of life, disease symptoms and control, treatment-related toxicities that could lead to discontinuation, treatment convenience (oral vs intravenous), and financial toxicity.

With high-risk myeloma, it is a disease that can be difficult to treat. To further complicate management, many patients are unable to receive intense treatment because of comorbidities.

At the Community Case Forum, Davis presented a case of a 76-year-old female with ISS stage II myeloma, who is not eligible for a transplant and also presents with early-stage Parkinson’s disease that is currently controlled with treatment. At diagnosis, she presented with severe lower back and neck pain, has experienced increasing fatigue and mobility challenges, and reported with an ECOG performance status of 1.

The case, Davis noted, highlights certain patients’ inability–for example, older, frail, or transplant-ineligible patients–to receive aggressive therapy, whether considered high risk or not, and, in turn, the need for treatment de-escalation.

The attendees were polled on what regimen should be prescribed for the frontline treatment of this patient, including:

bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (VRd), which included CRd lite;

daratumumab (Darzalex) plus lenalidomide and dexamethasone (Dara-Rd);

ixazomib (Ninlaro) plus lenalidomide and dexamethasone (Ixa-Rd); or

a quadruplet regimen like Dara-VRd or Dara-VMP)

Results were evenly divided-50% of respondents said that they would consider VRd while the other half were in favor of Dara-Rd.

“Both of those responses are on par to what we would expect,” Davis said. “…Frail and elderly patients are technically considered high-risk patients because historically, they’re unable to go with more aggressive therapies that include transplants.”

He added that these patients will also often be offered, in the community setting, a doublet that has inferior results due to concerns of toxicity. “More recent data from the MAIA study [NCT02252172]

 showed similar tolerance in older patients who were treated with Dara-RD vs Rd. Hopefully, this data will encourage clinicians to move further away from doublets even in our frail patients.”

Similarly, he added, often patients who are elderly or frail would not be offered a quadruplet regimen either. “You're often going to have to de-escalate [treatment] in some form or fashion.”

To aid in predicting long-term remission, the use of minimal residual disease (MRD) is growing in the multiple myeloma landscape.

“There's now studies ongoing about de-escalating therapy based on MRD, but also just even outside of that, from a prognostic value, it's more accurate than our M spikes,” Davis explained. “…MRD is most valuable when patients are wanting to de-escalate, and this could be a leverage point.”

In the case study, the patient was treated with frontline Dara-Rd. Following 9 months of treatment, she presented with an ECOG performance score of 2, a complete remission that was followed by a partial response at month 1 and very good partial response at month 8, with stable chemistry labs. In addition, the patient experienced grade 3 neutropenia that lasted for 1 cycle of treatment and appeared refractory to a single dose of granulocyte colony-stimulating factor. Her imaging revealed no new findings.

At 12 months, the patient’s ECOG performance score was 1 and she is stable in CR, chemisty and hematology labs, and continuance of no new findings on her imaging. Of note, her Parkinson’s disease remained in control with daily functioning that was consistent with baseline findings.

“MRD negativity at 12 months alone has also been associated with overall survival improvement. So again, it just highlights, for us, the relevance of deepening responses and maintaining somebody in a state of undetectable disease,” he said, highlighting that MRD negativity led to a median progression-free survival of 63 months, compared 27 months among patients with CR achievement, based on data from a pooled analysis of 3 Pethema/GemDavis clinical trials.

NCCN. Clinical Practice Guidelines in Oncology. Multiple myeloma, version 1.2025. Accessed December 12, 2024. 

https://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf

Facon T, Kumar S, Plesner T, et al. Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma. 

. 2019;380:2104-2115. doi:10.1056/NEJMoa1817249.

Lahuerta JJ, Paiva B, Vidriales MB, et al. Depth of Response in Multiple Myeloma: A Pooled Analysis of Three PETHEMA/GEM Clinical Trials. 

. 2017;35(25):2900-2910. doi:10.1200/JCO.2016.69.2517.

“Treatment effectiveness can have different meanings to patients,” a physician assistant said when discussing therapy for high-risk myeloma. 

High-Risk Myeloma Treatment Is Not One-Size-Fits-All

The use of bispecific antibodies have brought landmark change for the treatment of relapsed/refractory multiple myeloma, and tend to be well-tolerated, explained Carrie Lechtenberger, APRN, FNP-C, CCM, OCN, CBCN.

“[Bispecific antibodies] are exciting. What they do is great, and I think patients overall have pretty tolerable, if any, side effects,” Lechtenberger, a family nurse practitioner at Levine Cancer Institute, Atrium Health, said.

Making the Decision: Bispecifics Vs. CAR T-Cell Therapy in Myeloma

, Lechtenberger discussed the use of bispecific antibodies—which harness the immune system to find and fight cancerous cells—for patients with multiple myeloma. She discussed adverse effects from this class of drugs, and what nurses and advanced practice providers (APPs) should discuss with their patients before starting them on this type of therapy.

What does education about these drugs look like between the oncology nurses/APPs and the patients and their caregivers? What is important to know before starting bispecific antibody treatment?

Something that's important for patients to know is that although this is not your typical chemotherapy—you're not going to see that hair loss, or maybe the [gastrointestinal] side effects, or some of the things that chemotherapy can bring. [However], there still are side effects.

Bispecifics are working with your immune system. We are ramping up your immune system to identify the cancer, and so there are side effects involved with doing that. I still like to let patients know that you will experience [adverse effects]. Every person is different. It's impossible to say exactly what they'll experience. But I think it's important to teach patients and their loved ones what can be seen, what can be experienced, and what to do when they do experience those side effects.

What are some of the more common adverse effects that you see with bispecific antibodies?

I am a nurse practitioner who is mostly focused on the inpatient clientele. So I'm not first line in the infusion suite, but I am tied to the infusion suite, and so the goal is that I will carry over my role into both.

We mostly see patients with multiple myeloma getting treated with bispecifics here, their side effects [are] maybe a cytokine release syndrome (CRS) that could potentially be grade 1 or grade 2. It's not common, but it can happen. And [immune effector cell-associated neurotoxicity syndrome (ICANS)] can sometimes be something that a patient may deal with, [and can present as] some word-finding issues, confusion. And again, it's not highly common. Those can easily be treated, so we can hopefully mitigate that becoming worse.

What are some of the symptoms to look out for, indicating potential ICANS and CRS, and how is this treated?

So with CRS, sometimes you're going to get chills, or it could progress into rigors. It could be this…overall feeling of not feeling well, and the patient just suddenly feeling like they're declining.

Tocilizumab for CRS is usually a good go-to for the multiple myeloma patients. I think there's still some discussion over, do we do this also with the dexamethasone? Some people will say, yes. I think that that it's still really early, and I think sometimes it's hard to know.

But I would say the tocilizumab, [approximately] 8 mg, is usually a good place to start for that. A steroid seems to be what eventually is a good choice.

While bispecific antibodies tend to be well-tolerated for patients with multiple myeloma, there are still adverse effects clinicians should discuss with their patients. 

Bispecific Antibodies Are ‘Not Your Typical Chemotherapy’ in Myeloma Treatment

Belantamab mafodotin-blmf (Blenrep) plus carfilzomib, lenalidomide (Revlimid), and dexamethasone (a regimen known as KRd) demonstrated early evidence of deep responses, as well as a manageable adverse event profile in previously treated patients with multiple myeloma, according to data from a phase 1 trial (NCT04822337), presented at the 21st International Myeloma Society Annual Meeting.

Investigators determined the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of belantamab mafodotin in this regimen to be 1.9 mg/kg every 8 weeks.

The most common gastrointestinal (GI) adverse effects (AEs) seen with the combination across all treated patients (n = 19) included diarrhea (grade 1, 31.6%; grade 2, 15.8%), constipation (21.1%; 5.3%), vomiting (10.5%; 15.8%), nausea (10.5%; 21.1%), dysgeusia (5.3%; 5.3%), oral mucositis (5.3%; 5.3%), and anorexia (0%; 15.8%). No grade 3 or higher GI AEs were reported. Grade 3 and 4 hematological and infectious AEs included decreased platelet counts (grade 3, 5.3%; grade 4, 21.2%), decreased neutrophil counts (21.1%; not available [NA]), and all infections (15.8%; NA). Grade 1, 2, and 3 keratopathy was observed in 21.1%, 42.1%, and 31.6% of patients, respectively.

“Eye toxicity was reversible in all cases,” Shebli Atrash, MD, MS, FACP, said in the presentation. “It seems that the duration [of eye toxicities] was less than the previously seen eye toxicity in [the phase 2] DREAMM-2 [trial (NCT03525678)] …It’s important to note that [the rate of infections] sets this regimen apart from other BCMA-targeted approaches, including CAR T[-cell therapy] and bispecific [antibodies], given lower infection risks [with those agents].”

Atrash is a hematologist at the Atrium Health Levine Cancer Institute in Charlotte, North Caroline, as well as a clinical associate professor of hematology and oncology at the Wake Forest University School of Medicine in Winston-Salem.

Rationale for Investigating Belantamab Mafodotin-Based Quadruplets in Myeloma

Prior research has shown the feasibility of quadruplet regimens containing KRd plus transplant in patients with transplant-eligible, newly diagnosed multiple myeloma. For instance, in the phase 2 FORTE trial (NCT02203643), KRd in combination with autologous stem cell transplant (ASCT; n = 315) elicited at least a very good partial response (VGPR) after induction in 70% of patients vs 53% of patients who received carfilzomib plus cyclophosphamide and dexamethsone plus ASCT (odds ratio [OR], 2.14; 95% CI, 1.44-3.19; 

Furthermore, in the phase 3 IsKia trial (NCT04483739), rates of minimal residual disease (MRD) negativity at a sensitivity of 10–6 improved over time throughout all trial phases in patients who received Isa-KRd (n = 151) vs those who received KRd alone (n = 151).

 The post-induction, post-ASCT, and post-consolidation MRD-negativity rates in the Isa-KRd arm were 27%, 52%, and 67%, respectively. These respective rates were 14% (OR, 2.36; 

“All those results make us ask the question: Can we improve on the triplet regimen further?” Atrash asked.

Studies have also shown the efficacy of belantamab mafodotin in patients with relapsed/refractory multiple myeloma. In DREAMM-2, efficacy-evaluable patients who received the agent at 2.5 mg/kg (n = 97) achieved a median duration of response (DOR) of 11 months and an overall response rate (ORR) of 31% (97.5% CI, 20.8%-42.6%).

 Moreover, in the phase 3 DREAMM-7 trial (NCT04246047), belantamab mafodotin plus bortezomib (Velcade) and dexamethasone improved progression-free survival (PFS; HR, 0.41; 95% CI, 0.31-0.53; 

< .001) and OS vs daratumumab (Darzalex) plus bortezomib and dexamethasone in patients with multiple myeloma who had progressed on at least 1 prior line of therapy.

“Those results support the use of a quadruplet regimen with KRd with the addition of belantamab mafodotin,” Atrash noted.

Although DREAMM-2 showed that belantamab mafodotin is effective when administered every 3 weeks, the trial also demonstrated that the agent is associated with keratopathy, with similar rates of this AE observed regardless of the dose level.

Among safety-evaluable patients who received the agent at 2.5 mg/kg (n = 95), grade 3 keratopathy or changes to the corneal epithelium was observed was observed in 27% of patients. Among safety-evaluable patients who received the agent at 3.4 mg/kg (n = 99), grade 3 keratopathy or changes to the corneal epithelium was observed was reported in 21% of patients.

“The rates of blurred vision and dry eye improved with lower doses of belantamab mafodotin, suggesting better tolerability with lower doses,” Atrash said.

This phase 1 study of belantamab mafodotin plus KRd enrolled patients with relapsed/refractory multiple myeloma who had received at least 1 prior line of therapy and had measurable disease. Patients needed to have an ECOG performance status of 0 to 2; an ANC of at least 1.5 x 103/mm3 if their marrow burden was less than 50% or an absolute neutrophil count (ANC) of at least 1.0 x 103/mm3 if their marrow burden was higher than 50%; a platelet count of at least 100,000 cells/mm3; total bilirubin levels at or below 1.5 times the upper limit of normal (ULN); aspartate aminotransferase and alanine aminotransferase levels at or below 2.5 times the ULN; creatinine clearance levels of at least 30 mL/min; and a left ventricular ejection fraction higher than 40%.

This phase 1 study included a 3+3 dose-escalation portion followed by a dose-expansion cohort to identify the RP2D. The primary objective was to establish the MTD of belantamab mafodotin. Key secondary objectives included ORR, depth of response, DOR, PFS, OS, and safety.

Patients received belantamab mafodotin plus KRd for a maximum of 18 cycles, followed by lenalidomide maintenance. Patients remained on treatment until disease progression or toxicity. Intravenous (IV) belantamab mafodotin was tested at 2 doses: 1.4 mg/kg or 1.9 mg/kg each over 30 to 60 minutes every 8 weeks. A backbone regimen of KRd was administered in 28-day cycles and consisted of IV carfilzomib at 20 or 56 mg/m2 on days 1, 8, and 15; oral lenalidomide at 25 mg on days 1 through 21; and oral dexamethasone at 20 or 40 mg weekly.

During the dose-escalation portion, 3 patients received belantamab mafodotin at 1.4 mg/kg. One DLT of grade 4 thrombocytopenia was observed at this dose level.

“It’s important to note that the patient remained on the study and achieved MRD negativity later on,” Atrash added.

Three more patients were enrolled at the dose level of 1.4 mg/kg. No additional DLTs were observed at this dose level, and the dose was escalated in 3 additional patients to 1.9 mg/kg. No DLTs were observed at this dose level, and 3 more patients were enrolled at the 1.9-mg/kg dose level to identify the MTD. Investigators did not observe any DLTs at the 1.9-mg/kg dose level, and this was identified as the MTD.

Notably, patients had received a median of 1 prior line of therapy (range, 1-3), and 42.1% of patients were Black. International Staging System information was available for 15 patients, 40%, 26.7%, and 33.3% of whom had stage I, II, and III disease, respectively. High-risk cytogenetics were observed in 47.3% of patients, and included 1q gain and 1p deletion (5.3%), 17 deletion (10.5%), and 1q gain (36%). Among all patients, 42.1% were refractory to lenalidomide, 10.5% were refractory to bortezomib, 26.3% were double refractory to a proteasome inhibitor and an immunomodulatory agent, and 26.3% were refractory to daratumumab.

Beyond keratopathy, the most common ophthalmological AEs seen at any point during treatment included blurred vision (5.2%; 42.1%; 42.1%), dry eye (36.8%; 5.3%; NA), cataract (0%; 10.5%; NA), photophobia (10.5%; 0%; NA), and conjunctivitis (0%; 5.3%; NA). No grade 4 ophthalmological AEs were observed.

Regarding the number of patients dosed in each treatment cycle, during cycle 1 (n = 19), 100% of patients were given treatment. During cycles 3 (n = 18), 5 (n = 15), 7 (n = 13), 9 (n = 11), 11 (n = 11), 13 (n = 9), 15 (n = 8), and 17 (n = 7), 61%, 47%, 58%, 36%, 64%, 44%, 25%, and 57% of patients enrolled in each cycle received treatment. Reasons for non-treatment in each cycle included dose toxicity, defined as grade 2 or higher keratopathy prior to dosing, as well as patient choice, Atrash explained.

“Keratopathy was manageable mainly with dose delays and to a lesser degree, with dose reductions,” Atrash noted.

Best responses included stringent complete response (CR; 37%), CR (16%), VGPR (5%), and PR (42%).

“Regarding MRD negativity, 10 out of 19 patients so far have MRD negativity at 10–5, whereas 40% of the patients had MRD negativity at 10–6,” Atrash emphasized.

At a median follow-up of 16.8 months, 3 patients had progressed. The 24-month PFS, DOR, and OS rates were 80%, 81%, and 95%, respectively.

Based on these phase 1 findings, the phase 2 portion of the trial is planned, in which patients with high-risk, newly diagnosed multiple myeloma will undergo autologous stem cell transplant following induction with 8 cycles of belantamab mafodotin plus KRd.

Dr Atrash reports receiving research funding from Amgen, GSK, and Karyopharm; receiving honoraria from Janssen; and receiving consulting fees from Pfizer.

1. Atrash S. Results of a phase 1 clinical trial of belantamab mafodotin combined with carfilzomib, lenalidomide, and dexamethasone for multiple myeloma after one prior line of therapy. Presented at: 2024 International Myeloma Society Annual Meeting; September 25-28, 2024; Rio De Janeiro, Brazil. Abstract OA-57.

2. Gay F, Musto P, Rota-Scalabrini D, et al. Carfilzomib with cyclophosphamide and dexamethasone or lenalidomide and dexamethasone plus autologous transplantation or carfilzomib plus lenalidomide and dexamethasone, followed by maintenance with carfilzomib plus lenalidomide or lenalidomide alone for patients with newly diagnosed multiple myeloma (FORTE): a randomised, open-label, phase 2 trial. 

. 2021;22(12):1705-1720. doi:10.1016/S1470-2045(21)00535-0

3. Gay F, Roeloffzen W, Dimopoulos MA, et al. Results of the phase III randomized Iskia trial: isatuximab-carfilzomib-lenalidomide-dexamethasone vs carfilzomib-lenalidomide-dexamethasone as pre-transplant induction and post-transplant consolidation in newly diagnosed multiple myeloma patients. 

. 2023;142(suppl 1):4. doi:10.1182/blood-2023-177546

4. Lonial S, Lee HC, Badros A, et al. Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study. 

. 2020;21(2):207-221. doi:10.1016/S1470-2045(19)30788-0

5. Hungria V, Robak P, Hus M, et al. Belantamab mafodotin, bortezomib, and dexamethasone for multiple myeloma. 

. 2024;391(5):393-407. doi:10.1056/NEJMoa2405090

Belantamab mafodotin plus KRd had a a manageable safety profile and deep responses in pretreated multiple myeloma.

Belantamab Mafodotin, KRd Is Promising in Relapsed/Refractory Myeloma

Compared with 2 trials that led to its FDA approval, second-line treatment with lisocabtagene maraleucel (liso-cel; Breyanzi) demonstrated safety and efficacy outcomes that were comparable among patients with relapsed/refractory large B-cell lymphoma (LBCL), according to real-world findings.

Real-world treatment with liso-cel showed a broad spectrum of outcomes that were comparable to those in the pivotal TRANSFORM and PILOT trials in patients with relapsed/refractory large B-cell lymphoma.

Julian Adams, PhD

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