Ciltacabtagene autoleucel (Carvykti; cilta-cel) was approved by the FDA in February 2022

 for patients with relapsed or refractory multiple myeloma, potentially fulfilling an unmet medical need for the population, according to Thomas G. Martin, MD.

phase 1b/2 CARTITUDE-1 trial (NCT03548207)

 where patients were given a one-time treatment with cilta-cel, resulting in an overall response rate of 97.9% (95% CI, 92.7%-99.7%) at a median follow up of 18 months.

 Updated results from the trial were presented at the 

2021 American Society of Hematology Annual Meeting

. The majority of the population was considered heavily pretreated and triple-class refractory with a median of 6 prior lines of therapy. After 2 years, the progression-free survival (PFS) rate was 61% and the median PFS was not reached.

“We couldn’t be more excited about cilta-cel with the current data showing that 60.5% of patients remain in remission 24 months after initiation of therapy. We can’t wait to see what it is at 30 months, and maybe what it is at 36 months. All CAR T-cell therapeutics aim to have a flattening of the curve. Unfortunately, [for] patients who have the worst myeloma are the most resistant [and] relapse over time, there might be a tail end the curve or flattening of the curve. [These are] people who have prolonged remission duration, and some may be cured. We still don’t know from the cilta-cel PFS curve if there’s going to be a tail or if there are going to be some patients who have long remission durations for 5-plus years. If that’s true, that’s amazing,” Martin stated.

In an interview with CancerNetwork®, Martin, lead study investigator of CARTITUDE-1 and associate director of the myeloma program at the University of California San Francisco, discussed the importance of the approval, how it may address unmet patient needs, and future research directions.

What does the approval of cilta-cel in the treatment of recurrent or metastatic cervical cancer mean for this patient population?

 We have quite a few patients, over 50,000, who are in the US right now who currently have multiple myeloma. A large number of those [patients are] triple-class refractory. [Sometimes patients] have very few options left for good therapeutics that provided deep remission. We have 1 CAR T-cell product that’s currently approved for use, known as idecabtagene vicleucel [Abecma]. It has been very difficult to obtain manufacturing slots, or to obtain the therapy for people across the US, so the [approval of cilta-cel] is huge. There’s room for 2, 3, maybe even 4 different CAR T-cell therapeutics based on the number of slots that we need and the number of patients who currently will be eligible for this therapy.

In this in this triple-class refractory population, we do have some drugs that are available. For the drugs that are currently available, the response rates are in the order of 20% to 30%, so only 1 in 4, or maybe 1 in 3, [patients] will respond. When they respond, they tend to respond for anywhere between 5 and 11 months; they have a short time of response, unfortunately. We’re left to recycle some of the drugs that we had before, and sometimes we don’t have medicines that’ll work. That is an unmet need for patients who’ve received our 3 big classes of drugs. [They are] proteasome inhibitors, immunomodulatory drugs, and CD38 antibodies. When they received those [drugs] and [they] don’t work anymore, we need more therapies for those patients.

Which patients will benefit most from this therapy?

We try to look at what the difference between eligibility for an autologous transplant, eligibility for a CAR T-cell therapy, or [eligibility] for any off-the-shelf product. For most people who are older than age 70, or older than age 75 years, we have a difficult time [conducting] an autologous transplant because it’s a tough treatment.

CAR T-cells can be [manufactured for] patients who are 8 years old and patients who are in their mid 80s if that patient is fit. I [ask patients] ‘if you walk [the distance of] 2 telephone poles, do you need oxygen? If you don’t, do you get chest pain?’ If you don’t, you’re eligible for CAR T-cell therapy. We can make it so that a larger population than [those] who are eligible for an autologous transplant can get this CAR T-cell therapy. Anybody who is fit, age independent, [who can] walk into the doctor’s office, jump in the chair, jump up on doctors table, etc., is likely fit enough to go through CAR T-cell therapy. It’s going to be a broad patient population. That’s why the need is so high [for this treatment].

What are the next steps for researching this product in this patient population?

In this patient population, we must look into how we can make it a longer remission duration for everybody. The currently approved therapeutic idecabtagene vicleucel has a [median] progression-free survival [PFS] of 12 months. We would love for it to be longer than that, right? Maybe we need to do maintenance therapy. Maybe we need to see if we [give] treatment after we give the CAR T-cell therapy, something that can rev up the T-cells, make them last longer, and perhaps provide more of an anti-myeloma effect.

Cilta-cel has a longer PFS [according to data recently] presented at the recent 

63rd Annual American Society of Hematology Annual Meeting

 The 2-year PFS rate was 60.5%, so people are getting 2 years or more of remission duration. Can we even make it longer by adding [another agent]? That’s one avenue as to how to make it better for the people with relapsed, triple-class refractory [disease]. The other question for us is if we move it to earlier lines of therapy, will we be able to cure some patients with multiple myeloma? Will their remission duration be longer? If we do it in less heavily pretreated patients where their T-cells are healthier and when their myeloma isn’t as resistant, can we make it last longer? That’s a huge question, and that’s where a lot of the energy is now in proving those points.

U.S. FDA Approves CARVYKTI (ciltacabtagene autoleucel), Janssen's first cell therapy, a BCMA-directed CAR-T immunotherapy for the treatment of patients with relapsed or refractory multiple myeloma. News release. Janssen. February 28, 2022. Accessed February 28, 2022. https://prn.to/3vskiZu

Martin T, Usmani S, Berdeja J, et al. Updated results from CARTITUDE-1: Phase 1b/2 study of ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T cell therapy, in patients with relapsed/refractory multiple myeloma. Blood. 2021;138(suppl 1):549. doi:10.1182/blood-2021-146060

Articles

In an interview with CancerNetwork®, Thomas G. Martin spoke about how the approval of ciltacabtagene autoleucel will likely dramatically impact the standard of care for patients with relapsed/refractory multiple myeloma. 

Thomas G. Martin, MD, Discusses Approval of Cilta-Cel in R/R Multiple Myeloma

The FDA has approved the use of ciltacabtagene autoleucel (Carvykti; cilta-cel) for the treatment of patients with relapsed/refractory multiple myeloma after 4 or more lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, according to press release from The Janssen Pharmaceutical Companies of Johnson & Johnson.

The approval was based on findings from the phase 1b/2 CARTITUDE-1 trial (NCT03548207) during which one-time treatment with cilta-cel resulted in an overall response rate of 98% (95% CI, 92.7%-99.7%). Additionally, investigators reported a stringent complete response rate of 78% (95% CI, 68.8%-86.1%). The median duration of response was 21.8 months after a median follow-up of 18 months.

“We are committed to harnessing our science, deep disease understanding and capabilities to bring forward cell therapies like CARVYKTI as we continue to focus on our ultimate goal of delivering a cure for multiple myeloma,” Peter Lebowitz, MD, PhD, global therapeutic area head, of oncology at Janssen Research & Development, LLC. “We extend our sincere gratitude to the patients, their families and the teams of researchers and study centers who have participated in the clinical study of CARVYKTI and enabled today's approval.”

Updated results were previously presented at the 

2021 American Society of Clinical Oncology Annual Meeting

enrolled 97 patients, with a median turnaround time for cilta-cel therapy was 29 days. Patients had a median age of 61.0 years, and 58.8% (n = 57) were male. Additionally, patients had underwent a median of 6.0 lines of prior therapy. Moreover, 87.6% (n = 85) pf patients were triple-class refractory, and 42.3% (n = 41) were penta-drug refractory. Nearly all patients (99%; n = 96) were refractory to their last line of therapy.

BCMA-positive patients who were treated with CAR T-cell therapy experienced an overall response rate of 97.9% with a stringent complete response (sCR) rate of 80.4% and a very good partial response of 14.4%. The median time to first response was 1 month, and the median time to best response and CR or greater was 2.6 months. Moreover, the median duration of response was 21.8 months. Investigators estimated that 73% of responders had not progressed or died at 12 months.

A total of 61 patients were minimal residual disease (MRD) evaluable, 91.8% of whom were MRD negative, with a median time to MRD 10-5 negativity of 1 month. Investigators also reported that 57.7% of those in the overall patient population were MRD negative. Additionally, the overall patient population had an 18-month progression-free survival (PFS) rate of 66.0% (95% CI, 54.9%-75.0%), and those who achieved a sCR had an 18-month PFS rate of 75.9% (95% CI, 63.6%-84.5%). The 18-month overall survival rate was 80.9% (95% CI, 71.4%-87.6%).

Investigators did not observe any new safety signals with this follow-up. The most common grade 3/4 hematologic adverse effects (AEs) that occurred in 25% or more of patients included neutropenia (94.8%), anemia (68.0), thrombocytopenia (59.8%), and leukopenia (60.8%). The most common grade 3/4 nonhematologic AEs included hypophosphatemia (7.2%) and hypocalcemia (3.1%), with other AEs including fatigue (5.2%) and aspartate aminotransferase increase (5.2%).

Within the overall patient population, 94.8% (n = 92) of patients experienced cytokine release syndrome (CRS), with the time to median onset of 7 days and a median duration of 4 days. The majority of cases were grade 1/2, and 98.9% of patients had their CRS resolve within 14 days of onset.

“Cilta-cel has a manageable safety profile consistent with its mechanism of action; no new safety signals were observed with longer follow-up,” the investigators concluded.

Martin T, Usmani S, Berdeja J, et al. Updated Results from CARTITUDE-1: Phase 1b/2 study of ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T cell therapy, in patients with relapsed/refractory multiple myeloma. 

. 2021; 138(suppl_1): 549. doi:10.1182/blood-2021-146060

Patients with heavily pretreated relapsed/refractory multiple myeloma may now receive treatment with ciltacabtagene autoleucel following its approval by the FDA.  

FDA Approves Cilta-Cel for Relapsed/Refractory Multiple Myeloma 

In February 2022, the FDA approved ciltacabtagene autoleucel for the treatment of patients with relapsed/refractory multiple myeloma after 4 or more prior lines of therapy. 

Ciltacabtagene Autoleucel for Relapsed/Refractory Multiple Myeloma

Thomas Martin, MD, associate director of the myeloma program at the University of California San Francisco, spoke with CancerNetwork® about the approval of ciltacabtagene autoleucel (Carvykti; cilta-cel), which was based on the results of the phase 1b/2 CARTITUDE-1 trial (NCT03548207) in which patients with heavily pretreated multiple myeloma saw durable responses with the CAR T-cell therapy.

Martin also details why it’s such an important time for patients with multiple myeloma and how cilta-cel can help to improve outcomes.

We couldn’t be more excited about cilta-cel with the current data showing that 60.5% of patients remain in remission 24 months after initiation of therapy. We can’t wait to see what it is at 30 months, and maybe what it is at 36 months. All CAR T-cell therapeutics aim to have what we call a flattening of the curve. Whereas some people, unfortunately patients who have the worst myeloma are the most resistant, do relapse over time, there might be a what’s called a tail end the curve or flattening of the curve. [These are] people who have prolonged remission duration, and some that may be cured. We still don’t know from the cilta-cel PFS curve if there’s going to be a tail or if there are going to be some patients that have long remission durations for 5-plus years. If that’s true, that’s amazing.

1. U.S. FDA Approves CARVYKTI (ciltacabtagene autoleucel), Janssen's first cell therapy, a BCMA-directed CAR-T immunotherapy for the treatment of patients with relapsed or refractory multiple myeloma. News release. Janssen. February 28, 2022. Accessed February 28, 2022. https://prn.to/3vskiZu

2. Martin T, Usmani S, Berdeja J, et al. Updated Results from CARTITUDE-1: Phase 1b/2 study of ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T cell therapy, in patients with relapsed/refractory multiple myeloma. Blood. 2021;138(suppl 1):549. doi:10.1182/blood-2021-146060

Videos

Thomas Martin, MD, spoke about how the approval of ciltacabtagene autoleucel for patients with relapsed/refractory multiple myeloma may change the standard of care in this setting.

Thomas Martin, MD, on Excitement for a Cilta-Cel Approval in R/R Multiple Myeloma

Thomas Martin, MD, associate director of the myeloma program at the University of California San Francisco, spoke with CancerNetwork® about the approval of ciltacabtagene autoleucel (Carbykti; cilta-cel) and how investigators can best utilize this treatment for those with relapsed/refractory multiple myeloma.

 This approval comes based on the results of the phase 1b/2 CARTITUDE-1 trial (NCT03548207) in which patients with heavily pretreated multiple myeloma and were given cilta-cel and saw durable responses.

In this patient population, we must look into how we can make it a longer remission duration for everybody. The currently approved therapeutic idecabtagene vicleucel [Abecma] has a [median] progression-free survival [PFS] of 12 months. We would love for it to be longer than that, right? Maybe we need to do maintenance therapy. Maybe we need to see if we [give] treatment after we give the CAR T-cell therapy, something that can rev up the T-cells, make them last longer, and perhaps provide more of an anti-myeloma effect.

Cilta-cel has a longer PFS [with data recently] presented at the recent [63rd Annual American Society of Hematology Annual Meeting]. The 2-year progression-free survival rate was 60.5%, so people are getting 2 years or more of remission duration. Can we even make it longer by adding? That’s one avenue as to how to make it better for the people with relapsed, triple-class refractory [disease]. The other question for us is if we move it to earlier lines of therapy, will we be able to cure some patients with multiple myeloma? Will their remission duration be longer? If we do it in less heavily pretreated patients where their T-cells are healthier and when their myeloma isn’t as resistant, can we make it last longer? That’s a huge question, and that’s where a lot of the energy is now in proving those points.

Thomas Martin, MD, spoke about how to increase response durability with ciltacabtagene autoleucel for patients with heavily pretreated multiple myeloma.

Thomas Martin, MD, on Moving Forward With Cilta-Cel Treatment in Multiple Myeloma

Thomas Martin, MD, associate director of the myeloma program at the University of California San Francisco, spoke with CancerNetwork®about the approval of ciltacabtageneautoleucel (Carvykti; cilta-cel) and why it is important for patients with relapsed/refractory multiple myeloma.

 This approval is based on the results of the phase 1b/2 CARTITUDE-1 trial (NCT03548207) in which patients with heavily pretreated disease who were given cilta-cel saw durable responses.

He also discusses how cilta-cel has the potential to reduce the need for numerous lines of therapy.

We have quite a few patients, over 50,000, that that are in the US right now, that currently have multiple myeloma. A large number of those have what we call triple-class refractory. [Sometimes patients] have very few options left for good therapeutics that provided deep remission. We have 1 CAR T-cell product that’s currently approved for use, known as idecabtagenevicleucel [Abecma]. It’s been very difficult to obtain manufacturing slots, or to obtain the therapy for people across the US, so this [approval of cilta-cel] is huge. There’s room for 2, 3, maybe even 4 different CAR T-cell therapeutics based on the number of slots that we need and the number of patients that currently will be eligible for this therapy.

In this in this triple-class refractory population, we do have some drugs that are available. For the drugs that are currently available, the response rates are in the order of 20% to 30%, so only 1 in 4, or maybe 1 in 3, [patients] will respond. When they respond, they tend to respond for anywhere between 5 and 11 months; they have a short time of response, unfortunately. We’re left to recycle some of the drugs that we had before, and sometimes we don’t have medicines that’ll work. That is an unmet need for patients who’ve received what we call our 3 big classes of drugs. [They are]proteasome inhibitors, immunomodulatory drugs, and CD38 antibodies.When they received those and those don’t work anymore, we need more therapies for those patients.

U.S. FDA Approves CARVYKTI™ (ciltacabtagene autoleucel), Janssen's first cell therapy, a BCMA-directed CAR-T immunotherapy for the treatment of patients with relapsed or refractory multiple myeloma. News release. Janssen. February 28, 2022. Accessed February 28, 2022. https://prn.to/3vskiZu

Martin T, Usmani S, Berdeja J, et al. Updated Results from CARTITUDE-1: Phase 1b/2 study of ciltacabtageneautoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T cell therapy, in patients with relapsed/refractory multiple myeloma. Blood. 2021;138(suppl 1):549. doi:10.1182/blood-2021-146060

Thomas Martin, MD, spoke about the importance of the approval of ciltacabtagene autoleucel to treat patients with pretreated multiple myeloma.  