BRAIN CANCER

HER2-Positive 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

All News

FDA Briefs

Oncology Icons

Special Reports

Voices from the Field

CONFERENCES

Conference Coverage

Conference Listing

Data Dialogue with the Oncology Brothers

MEDIA

All Videos

Case-Based Peer Perspectives

Expert Perspective Virtual Tumor Board

Interviews

Investigator Perspectives

Medical World News

Pivotal Practice Views with the Oncology Brothers

Podcasts

Precision Medicine

Speaking Out

PUBLICATIONS

All Publications

Evolving Paradigms

Peers & Perspectives in Oncology

Targeted Therapies in Oncology

CASE-BASED ROUNDTABLE

PARTNERS

RESOURCES

CME/CE

Clinical Trials

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

Targeted Oncology - Immunotherapy, Biomarkers, and Cancer Pathways

Facebook

Linkedin

Twitter

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

Treating Later-Line Multiple Myeloma With CAR T-Cell Therapy

A 60-year-old woman was diagnosed with Revised International Staging System (R-ISS) stage II/R2-ISS stage III IgGκ multiple myeloma​.

Medical history: acute onset of renal insufficiency and hypercalcemia ​

Cytogenetics: 1q21+ amplification; t(14:16); high risk​

Patient declined autologous stem cell transplant.​

She received daratumumab (Darzalex), bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone, followed by lenalidomide maintenance.​

Best response: ​very good partial response (VGPR)

The patient experienced her first relapse​.

She continued lenalidomide maintenance therapy​.

On routine follow-up, she reported having mild fatigue but continued to work full-time​.

Bone marrow plasma cells, light chains, and M protein levels rising​

Kidney function worsening; estimated glomerular filtration rate: 22​

Following second relapse, the patient was initiated on daratumumab, carfilzomib (Kyprolis), and dexamethasone with a best response of VGPR.

After 2 prior lines of therapy​, the patient presented to her oncologist with complaints of increased fatigue and persistent bone pain in her lower back exacerbated by minimal movement​.

She expressed interest in chimeric antigen receptor (CAR) T-cell therapy with her clinical team.​

She also stated that she wants to travel out of the country for her daughter’s wedding in 3 months.

Targeted Oncology: Could you explain the design of the phase 3 KarMMa-3 trial (NCT03651128) and its significance in patients with relapsed/refractory multiple myeloma?

KarMMa-3, the trial of ide-cel [idecabtagene vicleucel; Abecma], enrolled patients who have had 2 to 4 prior lines of therapy, so [it did not include] the very early relapses with 1 prior line. They had to be refractory to the last regimen. It was a 2:1 randomization to ide-cel vs standard of care [SOC], and there were 5 different options. Very importantly, it was a crossover design. If you were randomly assigned to SOC, you could then cross over and get CAR T-cell therapy. This will become important because of the overall survival [OS] data [where] the curves don't separate out, probably because of crossover. 

Bridging therapy was optional; if I was the one designing the trial, I wouldn't design it like this. It was optional and [must be] 1 cycle or less with a minimum 14 -day washout. [A total of 225 of 254 patients in the experimental arm] received CAR T-cell therapy with 150 to 450 million cells in the CAR T-cell arm. The patients in the comparator arm received standard regimens until progression. Over 200 patients received CAR T-cell therapy, and 126 patients received SOC. The primary end point was progression-free survival [PFS] and secondary end points were overall response rate [ORR], OS, etc.

The big picture is that the characteristics were well balanced [between the arms].

 Over 90% of these patients were daratumumab refractory, 95% and 93% [in the experimental and SOC arms, respectively], which tells you this is a very heavily treated population. The median number of prior lines of therapy for this trial was 3, so even though it's an earlier trial [than the prior KarMMa trial (NCT03361748)], it's not an early-line trial. The median number of lines of therapy for the initial approval was 5 and this is 3, so most patients had exhausted conventional options by this time point. it's important to keep this in mind because the results do look different between the 2 trials.

What were the key efficacy outcomes in this trial?

This trial was positive, meeting its primary end point for PFS.

 The median PFS for the CAR T-cell therapy arm was almost 14 months, and the median PFS for the SOC arm was 4 months. So SOC did just as I would have expect it to do [in patients with] 3 prior lines of therapy. The CAR T-cell therapy arm did better than what ide-cel results showed in the fifth-line setting, which was a median of 9 months of PFS.

The ORR was also better in the ide-cel arm, 71% vs 42%. The control arm did just as I would have expected; we expect an ORR of 30% to 40% at this stage. This is almost 2 times [better], which is great. The complete response rate was 44% with ide-cel vs 5% in SOC. When patients get a response, many of them get a deep response with CAR T-cell therapy. Even the PFS2, which is the PFS with the next line of therapy, was 23.5 months and with the SOC regimens was 16 months. These patients did better [with ide-cel than SOC] combined with the next line of therapy even though crossover was possible.

1. Rodriguez-Otero P, Ailawadhi S, Arnulf B, et al. Ide-cel or standard regimens in relapsed and refractory multiple myeloma. 

. 2023;388(11):1002-1014. doi:10.1056/NEJMoa2213614

2. Rodriguez-Otero P, Ailawadhi S, Arnulf B, et al. Idecabtagene vicleucel (ide-cel) versus standard (std) regimens in patients (pts) with triple-class–exposed (TCE) relapsed and refractory multiple myeloma (RRMM): updated analysis from KarMMa-3. 

. 2023;142(suppl 1):1028. doi:10.1182/blood-2023-178933

During a Case-Based Roundtable® event, Surbhi Sidana, MD, discussed the KarMMa-3 trial of earlier-line CAR T-cell therapy in patients with relapsed/refractory multiple myeloma in the first article of a 2-part series.

Ide-cel Shows Efficacy Earlier in R/R Multiple Myeloma Despite Crossover

Targeted Oncology: What has been the response to idecabtagene vicleucel (ide-cel; Abecma) for patients with multiple myeloma on a bridging therapy prior to this treatment?

of the phase 3 KarMMa-3 study (NCT03651128) data

] of what happens when the patient gets bridging therapy then gets their chimeric antigen receptor [CAR] T-cell therapy.

 [Investigators wanted to see if] patients responded or didn’t respond during bridging therapy, and [what they saw was their disease burden grew while bridging to CAR T-cell therapy, in some cases]…. Physicians have also looked at maintenance therapy and other strategies after CAR T-cell therapy to help it work even better, but for now, it's just 1 dose [of ide-cel that’s] given.

 But when was the last time we can recall patients with multiple myeloma being away from the clinic for a year [without needing additional] therapy? It's changing the [treatment] algorithm.

What adverse events (AEs) associated with ide-cel should be noted?

The most important AE to highlight was that 88% [of patients experienced] cytokine release syndrome [CRS] at any grade, but 4% [had grade 3 or 4 CRS, and there were 2 deaths]...on the study overall.2 Any-grade neurotoxic events were seen in 15%, while high-grade neurotoxic events were seen in 3%.

 It's not the perfect therapy, but these are now becoming more manageable toxicities as we're becoming more aggressive with prophylaxis [treatment]…alongside debulking the patient’s disease as much as we can prior to the therapy.

We're finding ways to make this treatment better [and more tolerable]. I think we also have a better understanding of how to support them from an infection perspective. Sometimes, we run into issues with cytopenia, and their white blood cell count might measure low, but in my experience, they come back up after a period of time. For example, there are some patients we’ve had to rescue with their stored stem cells to bring up their platelet counts, but these are all the things we're learning to improve outcomes with CAR T-cell therapy.

How has ide-cel performed in the real-world setting?

[Looking at] quality-of-life data, many recorded negative symptoms decreased while all positive measurements got even better.

 They've even done real world analyses of outcomes with ide-cel. This is…[focused on] the later line data after the fourth-line therapy, and the CRS rates in the clinic are similar between the trials, [along with] neurotoxic events.

 The trial patients did do better compared with what we see in the clinic, and that might [have to do with] opening the floodgates [in the real-world setting].

Patients [in the real-world setting are] on, for example, their tenth line of therapy and they're not going to do as well as [the patient on] their fourth line of therapy. If they've had a prior B-cell maturation antigen therapy, like belantamab mafodotin [Blenrep], in the clinic and then you send for CAR T-cell therapy, will they respond to it? Yes, they will; it's not as great as a response at [approximately] 71%, but those are still pretty good odds of responding to the BCMA CAR T-cell therapy.

 Depending on the type of prior BCMA therapy there's also differences [in outcomes], but I think if you have a patient who's gotten something like teclistamab-cqyv [Tecvayli] and then you're thinking [about what you would] still use down the line, CAR T-cell therapy is not an unreasonable option.

1. Einsele H, Rodriguez-Otero P, Arnulf B, et al. Idecabtagene vicleucel (ide-cel) versus standard regimens in triple-class-exposed relapsed and refractory multiple myeloma: KarMMa-3 subgroup analysis in patients receiving bridging therapy. Presented at: 2023 International Myeloma Society Annual Meeting; September 27-30, 2023; Athens, Greece. Abstract P-0008

2. Rodriguez-Otero P, Ailawadhi S, Arnulf B, et al. Ide-cel or standard regimens in relapsed and refractory multiple myeloma. 

3. Delforge M, Patel K, Eliason L, et al. Effects of idecabtagene vicleucel (Ide-Cel) versus standard regimens on health-related quality of life (HRQoL) in patients with relapsed/refractory multiple myeloma (RRMM) who had received 2-4 prior regimens: updated results from the phase 3 KarMMa-3 trial. 

. 2023;142(suppl 1):96. doi:10.1182/blood-2023-179152

4. Sidana S, Ahmed N, Akhtar OS, et al. Real world outcomes with idecabtagene vicleucel (Ide-Cel) CAR-T cell therapy for relapsed/refractory multiple myeloma. 

. 2023;142(suppl 1):1027. doi:10.1182/blood-2023-181762

During a Case-Based Roundtable® event, Abdullah Khan, MBBS, discussed the different outcomes with idecabtagene vicleucel in patients with relapsed/refractory multiple myeloma in both the clinic and real-world settings in the second article of a 2-part series. 

How BCMA CAR T-Cell Therapy Provides Later-Line Options in R/R Multiple Myeloma

Targeted Oncology: Please describe the phase 3 KarMMa-3 study (NCT03651128).

: This was our first phase 3 B-cell maturation antigen [BCMA] chimeric antigen receptor [CAR] T-cell therapy study in patients who had 2 to 4 prior lines of therapy.

 Patients were randomly assigned to either idecabtagene vicleucel (ide-cel; Abecma) or [a selection of standard regimens chosen by the physician]. The [standard regimens were] specified as they could either get bridging therapy with that therapy until [the patient’s] CAR T-cells were manufactured and sent back to the institution. The primary end point was progression-free survival [PFS], and these data were published in the 

What prior regimens did the patients on this study receive?

There were European and North American patients [recruited for the study, so this impacted the use of prior therapy] as we saw thalidomide and other therapies like that used previously.

Generally, there was a very high use of immunomodulatory drugs, proteasome inhibitors, and a lot of these patients also had transplants, but 95% were refractory to daratumumab [Darzalex].

 These were standard patients with multiple myeloma [who had a] second relapse.

How do you consider treatment for patients with relapsed/refractory multiple myeloma referred to you?

Presumably, [the patient was] referred to us because they're relapsing on their last regimen. We can probably come up with a good bridging regimen, but for some patients, where they're running out of options, [we need to just give them] something. But I don't think that’s [the case as much] anymore; I think we're able to salvage the patients a little bit better. Now, if [the patient's disease burden is] growing while we're waiting for their CAR T-cells, that's probably a bad outcome anyways. But if you're able to somehow decrease that disease burden [ahead of time] then the patient will do better, so don't go into CAR T-cell therapy [when the patient's disease burden is] increasing—have some disease control first.

What were the main efficacy results of the KarMMa-3 study?

In the final PFS analysis...the median PFS with [ide-cel] was 13.8 months [range, 11.8-16.1] compared with [the standard regimen arm] at 4.4 months [range, 3.4-5.8], which were excellent results and had a HR of 0.49 [95% CI, 0.38-0.63].

 I don't think we have the same [length] observed in lymphoma…but it’s a pretty good curve compared with the standard regimen arm. I think it just needs a longer follow-up. 

The depth of response was also significantly better with ide-cel vs chemotherapy [with an overall response rate of] 71% [95% CI, 66%-77%] vs 42% [95% CI, 34%-51%], respectively. Then the stringent complete response rates [sCR] of 41% [in the ide-cel arm were greater than the 5% in the standard regimen arm]. So, the depth and the quality of the response with CAR T-cell therapy is significantly better than [the standard regimens]. This also included achieving better minimal residual disease [MRD] negative CR rates [as well]. The researchers [had a smaller number of patients to] check, but a 35% [95% CI, 28%-42%] MRD negative CR rate vs 2% [95% CI, 0%-5%] for patients with 2 to 4 prior lines of therapy [is a] pretty good rate of attaining MRD negativity.

1. Rodriguez-Otero P, Ailawadhi S, Arnulf B, et al. Ide-cel or standard regimens in relapsed and refractory multiple myeloma. 

2. Rodriguez-Otero P, Ailawadhi S, Arnulf B, et al. Idecabtagene vicleucel (ide-cel) versus standard (std) regimens in patients (pts) with triple-class-exposed (TCE) relapsed and refractory multiple myeloma (RRMM): updated analysis from KarMMa-3. 

. 2023;142(1):1028. doi:10.1182/blood-2023-178933

During a Case-Based Roundtable® event, Abdullah Khan, MBBS, discussed the benefits of using CAR T-cell therapy in patients with relapsed/refractory multiple myeloma in the first article of a 2-part series. 

CAR T-Cell Therapy Significantly Impacts R/R Multiple Myeloma

video of Dr Khan discussing ide-cel and the KarMMa-3 trial

Updated Trial and Real-World Data Show Benefit of Ide-Cel for Multiple Myeloma

Abdullah M. Khan, MBBS, assistant professor in the division of hematology at The Ohio State University Comprehensive Cancer Center – The James, discusses the recent updates to data on the use of idecabtagene vicleucel (ide-cel; Abecma) in patients with relapsed/refractory multiple myeloma.

Updated data from the pivotal phase 3 KarMMa-3 trial (NCT03651128), which led to the approval of this chimeric antigen receptor T-cell therapy, were reported at the 2023 American Society of Hematology Annual Meeting & Exposition. At a follow-up of 30.9 months, investigators reported interim overall survival (OS) data, showing that the median OS was 41.4 months with ide-cel vs 37.9 months in the standard therapy group.

Additionally, Khan noted that real-world evidence with ide-cel was reported in the 

 in 2023, supporting its use in patients who do not necessarily match the stringent patient eligibility requirements of a clinical trial. For the 159 patients who received ide-cel, the best overall response rate was 84% and median progression-free survival (PFS) was 8.5 months (95% CI, 6.5-not reached), whereas median OS was 12.5 months (95% CI, 11.3-not reached).

According to Khan, these are both promising sources of data showing the benefit of ide-cel including in patients with comorbidities who are treated with CAR T-cell therapy in the real world.

 I wanted to give a little bit of updated data from the ASH 2023 conference. We actually have survival data for the KarMMa-3 trial with a longer follow-up of about 31 months. What they were able to show was the median OS in the ide-cel group was 41.4 months vs 37.9 months in the standard [therapy] group.

 There was also recent publication talking about ide-cel in the real world. Real world means that inclusion and exclusion criteria that are pretty stringent in trial design, we're applying less of those rules toward the patients we see in our clinic. And in a recent publication in JCO in 2023, in 159 patients, what they showed was response rates were also very impressive, about 84%. …In these less ideal patients…in terms of trial candidacy, median PFS was 8.5 months, and the median OS was 12.5 months. Again, very promising data, not just in the trial, but also real-world data.

Abdullah M. Khan, MBBS, discusses the recent updates to data on the use of idecabtagene vicleucel in patients with relapsed/refractory multiple myeloma. 