Deep Dive—On-Body Injectors vs Intravenous Administration

Expert oncologists discuss subcutaneous on-body injection vs intravenous administration during multiple myeloma treatment through the lens of the phase 3 IRAKLIA trial. 

To learn more, view the full series: Subcutaneous Solutions: The Evolving Landscape of Drug Administration in Multiple Myeloma Care. 

Dr Sikander Ailawadhi: Hello everyone, and welcome to continuing this series on on-body injectors. So, I'm Sikander Ailawadhi from Mayo Clinic in Florida, and I'm joined with my colleagues, Dr Joe Mikhael and Dr Beth Faiman. As you've heard previously in the previous chapter about just laying out the changing landscape of how drug delivery is given in cancer patients, this particular chapter from the series of Subcutaneous Solutions: The Evolving Landscape of Drug Administration in Multiple Myeloma Care. This chapter is talking about a deep dive on on-body injectors versus intravenous administration. In this chapter, we are mostly focusing on the IRAKLIA clinical trial, which was a global randomized open label, phase 3 non-inferiority study comparing isatuximab subcutaneous administration via an on-body injector device and isatuximab IV in combination with pomalidomide and dexamethasone in patients with relapsed or refractory myeloma.  

These patients had at least 1 prior line of treatment, and this study, which was a non-inferiority design, basically compared the difference between this on-body injector, isatuximab and the IV in that standard combination with pom- and dex-. So, getting directly to the clinical trial then, Joe, maybe I'll start by asking you, this study was a non-inferiority design, which is a little unusual for the types of studies we look at in cancer care, where we are so used to seeing the PFS curves, differences, one being so far apart from the other. In your mind, what was the importance of this study, the way it was set up, and what did the primary efficacy endpoint or results show us about this on-body injector?  

Dr Joseph Mikhael: Great. Yeah, that was a wonderful introduction, Sikander. You're absolutely right. It is not the kind of design that we're always as accustomed to, but the key point here was to say, if we're going to shift from the traditional use of IV now to being given through this on-body injector device subcutaneously, can we see that they are essentially equivalent both in their efficacy? Then ultimately, I think we'll hear a bit more from Beth on the safety. So, with regards to efficacy, there were 2 primary endpoints, and one was just the objective response rate, what we expect as the response rate. And thankfully, they were essentially identical. With the subcutaneous, it was a 71.1%. With the IV, it was 70.5%, and that was statistically significant for as you noted, the non-inferiority design with a really very low P value. Secondly, they also wanted to look at how the drug was concentrated prior to starting key doses in particular at cycle 6, day 1.  

So, are we not only seeing the response rate, but are we seeing the drug metabolized in the system and measured in the system? And again, the differences were met, the non-inferiority metric. There were several other secondary endpoints I won't get into in a lot of detail, but as we know, response rate means something, but a deeper response means something. So, they looked at V-G-P-R or very good partial response, and again, with the SUBQ, it was 46.4%. With the IV, it was 45.9%. Again, meeting that metric, as did the dosing as well as the concentration. That situation checked it at cycle 2, day 1. Then lastly, you commented to yourself, of course, how us oncologists were so prone to looking at PFS curves that they did look at progression-free survival at 12 months. Again, almost identical: subcutaneous 66.1% versus the IV at 65.1%. So really, to summarize the efficacy, we really don't see a difference between administering this drug, IV or subcutaneous. So, we'd be comfortable ultimately moving forward from a pure efficacy standpoint to give it in the way that it was given in the trial in the subcutaneous arm.  

Dr Sikander Ailawadhi: Excellent. Joe, thanks a lot for summarizing all those endpoints and numbers so nicely. You're so spot on that we're not used to seeing these kinds of studies. But finally, this design was not meant to show the difference. It was hoping that there was no difference, and that's what it actually showed. So, Beth, then coming to you put on your nursing hat, and please walk us through all these drugs work similarly, but is it really safe to give the patient the drug in this format? And was there anything where the on-body injector did anything better, similar to, or potentially worse than the IV version?  

Dr Beth Faiman: Yeah, absolutely. That's a very fair question. I think when I have a new product with a similar formulation, IV versus SUBQ, I want to know that it's not much different. So, that non-inferiority data is very important, but also the safety. What resonates with me, and we saw this with the other monoclonal antibody that was given SUBQ, which started out as IV, was the infusion-related reaction. So, when you're educating your patient on the side effects and the risks, you have to go through the hypersensitivity reaction that's observed in the very earlier doses, usually. What we saw in the isatuximab IV arm with the Isa-Pd, like the ICARIA study, was 25% infusion-related reaction versus 1.5%. So, that's so reassuring to see that there wasn't an increase in infusion related reactions, and most of these were grade 1 or 2 and generally resolved. I think that, for me, that's really important, and it resonates when I'm talking to the patients.  

Also, I think, are they happy with the treatment? I think we'll dive into this a little bit deeper later on. But for the IV versus SUBQ, as you imagine, think about getting an IV, you have to get it into a vein. Sometimes it's hard to find the veins, and then they have to get multiple sticks with blood draws as well. That tended to be, in this study, patients were in the intent-to-treat population satisfied with their treatment, the SUBQ 70% versus the IV formulation 53.4%. So, not only do we see less infusion-related reactions, similar safety profile to the intravenous, other than that infusion reaction, but also patient satisfaction as well.  

Dr Sikander Ailawadhi: Excellent. I guess there's a reason why I became a doctor because by default I didn't want to be an engineer, and now I'm being talked to about a device in the process of giving a cancer treatment. I think one of the questions that would come in the minds of our listeners would be, well, what do I do if the device doesn't work? From that standpoint, it was very reassuring to see that this device worked in about 99.9% of cases. So, almost none of them had any failures. That gives us a sigh of relief that I don't have to try to tinker with it or become an engineer or bring out my tools to fix it. So, we don't need to. I think the other thing, which I thought was very good to see was that the median time to give the drug or the drug administration was about 13 minutes, but everything happened under 20 minutes.  

There were no infusions that took longer than 20 minutes. Again, we have a limited time duration, very dependable success rate and a fixed dose that is being given to the patients. So, that is all kind of bringing in that convenience hat. I really appreciate both of you summarizing so much information, so much results in such a succinct manner. Once again, I want to thank all of our audience who are listening to this discussion, and thanks to my colleagues, Dr Joe Mikhael and Dr Beth Faiman, and I would like to keep encouraging you to please continue to the subsequent chapters. In fact, the next chapter is taking a deep dive on on-body injector versus the traditional subcutaneous administration. While over here, we talked about on-body versus IV, the next chapter is taking us one step further into comparing the on-body injector with the traditional subcutaneous administration. Thanks a lot for listening, and we look forward to your continued participation. 

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Sikander Ailawadhi, MD 
Dr Sikander Ailawadhi is a professor with the Division of Hematology-Oncology at Mayo Clinic in Jacksonville, Florida. His career focus has been on the treatment of plasma cell disorders with core research efforts in understanding the epidemiology and pathophysiology of these disorders and evaluating the benefit of various therapeutic strategies in different populations based on racial-ethnic and socioeconomic diversity. He has worked on the development of novel therapeutics by means of conducting several phase 1 through phase 3 clinical trials for novel drugs, including cellular therapy such as CAR T-cell treatment. Dr Ailawadhi also leads Mayo Clinic’s International Cancer Center and is focused on expanding and implementing the Mayo model of care and vision across the world. 

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Joseph Mikhael MD, MEd, FRCPC, FACP, FASCO 
Dr Joseph Mikhael is a professor in the Clinical Genomics and Therapeutics Division at the Translational Genomics Research Institute (TGen), an affiliate of City of Hope Cancer Center. He is also the chief medical officer of the International Myeloma Foundation (IMF) and director of myeloma research at the HonorHealth Research Institute. He is the principal investigator of many clinical trials, primarily in relapsed multiple myeloma. Dr Mikhael also serves as the treasurer on the executive board of the American Society of Hematology. Dr Mikhael has published over 200 peer-reviewed articles and lectures internationally on a regular basis. He leads the IMF’s diversity efforts, namely the M-Power project in the African American community. He is also the chair of the Diversity, Equity, and Inclusion Council at TGen. Dr Mikhael is heavily involved in training future researchers, mentoring junior faculty, and finding ways to enhance access to novel agents worldwide. 

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Beth Faiman, PhD, MSN, APN-BC, BMTCN, AOCN, FAAN, FAPO 
Dr Beth Faiman is an adult nurse practitioner in the Department of Hematology/Oncology at the Cleveland Clinic, a Case Comprehensive Cancer Center member under the Cancer Prevention, Control, and Population Research Program, and editor-in-chief of the Journal of the Advanced Practitioner in Oncology. She is also the editor of several books and author of numerous chapters and papers. In 2013, Dr Faiman was co-chair of the first Nursing Symposium at the International Myeloma Workshop and subsequent conferences. She has served on the American Board of Internal Medicine Maintenance of Certification Committee and as associate editor of the American Society of Hematology Clinical News. In 2023, Dr Faiman was given the NP/PA Educator of Distinction Award in Multiple Myeloma, and in 2022, she was named the Top NP in Hematology/Oncology and inducted as an inaugural Fellow of Advanced Practice in Oncology. Dr Faiman is a distinguished fellow in the American Academy of Nursing. She remains an active author, presenter, mentor, and educator on hematology, oncology, cellular therapies, and supportive cancer care.