Excitement Around FDA Approval of CARVYKTI as a Second CAR T Therapy

Week in Review
car t cell illustration

On February 28, 2022, the Janssen Pharmaceutical Companies of Johnson & Johnson announced that the U.S. Food and Drug Administration (FDA) has approved CARVYKTI™ (ciltacabtagene autoleucel; cilta-cel) “for the treatment of adults with relapsed or refractory multiple myeloma (RRMM) after four or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.”

“Through a phased approach, Janssen and Legend Biotech will activate a limited network of certified treatment centers as the company works to scale its production capacity and increase the availability of CARVYKTI™ throughout the U.S. in 2022 and beyond, to ensure that we can provide CARVYKTI™ treatment to oncologists and their patients in a reliable and timely manner,” states Janssen in the announcement press release.

Implications for Myeloma Community


The high level of excitement around the approval of this second Chimeric Antigen Receptor (CAR) T-cell therapy product (the first being ABECMA® (idecabtagene vicleucel) is for several reasons:

  • Game-changing therapies sustained deep responses

CAR T therapies administer the patient’s own T cells, which have been engineered to fight against myeloma using the BCMA surface target. CAR T therapies produce responses which are deeper and more long-lasting than any prior approach. With the recent approval of Carvykti, 98% of patients achieved deep responses; short- and longer-term toxicities/side effects were manageable — this is unheard of, for any new therapy. Typically, approximately 30% of patients refractory to prior therapies respond yet, frequently, the responses are not as deep nor as long-lasting. 

  •  ‘One and done’ approach

In addition, CAR T therapies use the “one and done” approach — a one-time infusion which produces an immediate and ongoing benefit. The infused engineered CAR T cells persist in circulation for a variable length of time to assist in achieving durable responses. 

In contrast, for antibody therapies (including Anti CD 38 antibodies, daratumumab and isatuximab) and the newer bi-specific antibodies (such as teclistamab, which targets BCMA-like CAR T cells), there is a need for ongoing therapy — typically for a minimum of 6 months or longer.



  • Need for specialized centers

Perhaps the major negative about CAR T therapies concerns access, as emphasized by Janssen: in their press release: “Through a phased approach, Janssen and Legend Biotech will activate a limited network of certified treatment centers as the company works to scale its production capacity and increase the availability of CARVYKTI™ throughout the U.S. in 2022 and beyond, to ensure that we can provide CARVYKTI™ treatment to oncologists and their patients in a reliable and timely manner.”

Thus, it will take time for CAR T-cell therapies to become broadly available (similar to what we’ve seen with the Abecma CAR T therapy). Hopefully, access issues will improve over time.

  • Patient eligibility

Currently, CAR T therapy products are approved for patients with relapsed and/or refractory multiple myeloma (RRMM). 

It is remarkable how well CAR T cells work in this setting. However, it is understandable that patients with earlier disease can see the potential benefit and are also very keen to have access. 

Studies are still ongoing and approval for earlier settings will take time. For the time being, patience is key when it comes to CAR T therapies. We certainly need to have close ongoing assessment of both efficacy plus short and longer-term toxicities or side effects in order to make the best decisions.



Bottom line

As outlined by Dr. Tom Martin during his February 26 presentation for the IMF Patient and Family Webinar , the availability of CAR T therapies opens a new frontier in treatment options for myeloma.


A single infusion is able to produce a dramatic benefit and changes the way we need to think about everything — from primary (frontline) therapy, the role of ASCT, and maintenance treatments.

•    Will we switch from ASCT to CAR T therapy? 
•    Will consolidation and / or maintenance be required? 

Clearly, testing for MRD (minimal residual disease) will become much more important as we assess the depth of responses achieved on a more routine basis. 
I believe that the myeloma treatment landscape will continue changing for the better, as we evaluate the new and important role of cellular therapies (such as CAR T) as well as other powerful new immune therapies in development (such as bi-specifics) which are likely to be approved soon. 

The current CAR T therapies are first generation cellular therapies. It is very exciting to think that more effective and better-tolerated products are almost certainly on the way. The new frontier of immune therapies is, indeed, full of hope for all myeloma patients and the whole myeloma community.
 


Source URL: https://www.myeloma.org/blog/excitement-around-fda-approval-carvykti-second-car-t-therapy