Isatuximab OBI Cuts Infusion Reactions: Xavier Leleu, MD, PhD

On June 8, 2026, the European Commission (EC) approved subcutaneous (subQ) isatuximab (Sarclisa; Sanofi) delivered through the CirCLIQ on-body injector (OBI) for use across all existing multiple myeloma (MM) indications in the European Union (EU), expanding options beyond intravenous (IV) administration. The decision was supported by data from the phase 3 IRAKLIA (NCT05405166) and phase 2 IZALCO (NCT05704049) trials, detailed in the cross-trial safety analysis “Safety and Reliability of Isatuximab Subcutaneous On-Body Injector: Results Across the Phase 3 IRAKLIA, Phase 2 IZALCO, and Phase 1B TCD15484 Trials,” released alongside the abstract published in conjunction with the European Hematology Association 2026 Congress.

Pooled results from 349 patients and 6426 injections showed infusion-related reactions in less than 1% of administrations, well below rates seen with IV or manual-push subQ formulations, with nearly all events graded mild and none leading to discontinuation. The device also completed 99.9% of injections without interruption. At the meeting, The American Journal of Managed Care^® spoke with Xavier Leleu, MD, PhD, lead IRAKLIA investigator and lead author of the analysis, about what the approval and these safety findings mean for patients, care teams, and the future of at-home myeloma treatment.

This interview was lightly edited for clarity.

AJMC: Recently, the EC approved the isatuximab OBI for subQ administration. What does this approval mean for patients in practice?

Leleu: We have demonstrated in myeloma up front in the relapse setting, but particularly up front, if we wanted to prolong survival [with] the disease and really match the promise we make to the patient that it is a chronic disease but we can have the patient not die from myeloma at all, ever, the CD38 monoclonal antibodies were part of the regimens needed to get to that objective. Isatuximab, the second one that has been developed, has proved safe and very active for the patients, particularly in the quadruplet-based regimen we have developed recently to propose a very prolonged survival.

The thing is that, as for any other drug, particularly immunotherapy, initially it was developed as an IV administration, which is great because it helps demonstrate and develop the product. But in the end, if you really want to be 100% convenient for patients and for the centers that treat the patients, you have to move to a subQ formulation. Something simpler, faster, safer, and more convenient. What was very interesting with the isatuximab story and its subQ formulation was that it could have been simply a manual push subQ formulation, as to any other subQ formulation I have tested in my life—24 years doing myeloma—and here there is an incredible innovation, which I didn’t initially [think] we could be smart in improving the subQ formulation. This OBI is very interesting because it’s not just a fancy subQ formulation. It’s safer. It’s even more convenient. It’s hard to believe that it’s even more convenient.

AJMC: Across more than 6400 injections in this cross-trial analysis, infusion-related reactions occurred in just 0.09% of administrations, while injection-site reactions remained uncommon and largely mild. What do these results tell us about the safety and tolerability of subQ isatuximab delivered via OBI?

Leleu: This is very important, because if we want to improve really the convenience of the treatment, we need to make sure that the first injection—the one that is a tricky one, because it’s this injection where we are more likely to see a systemic infusion reaction—[that we] control that event, that issue, because we need to make sure that the patient can be released from the hospital or outpatient clinic, or potentially the treatment be given at home, which would be even better. If we want to do that, we need to minimize, as best we can, these events, [these] infusion reactions.

We’ve been extremely happy to see that, with an IV infusion, more than 25% of the patients have this infusion reaction. With a manual push subQ, approximately 5% to 10% [of patients] have this infusion reaction. We have to keep all of the patients, because of the 5% to 10% of them having this reaction with the OBI, less than 1% of the patients, less than 1% of the infusions, had this infusion reaction, which now really makes that treatment, starting with day 1, cycle 1, I believe, manageable as an outpatient without having to keep the patient further or immediately at home. It might really be a great change for the patients at the centers.

AJMC: The injector successfully completed 99.9% of more than 6400 administrations, with potential for future at-home use. Considering this finding and the recent EU approval, what role do you see the subQ delivery of isatuximab via OBI playing in the evolving treatment landscape for patients with relapsed/refractory MM, both in Europe and globally?

Leleu: I hope it will be globally, but definitely in Europe, because I know more [about] the European market and how it works in Europe. The OBI is, by definition, the treatment you can give at home. The OBI will not only be given at home; it will also save time for the physicians, the nurse, and the pharmacist. Right now, we have 2 things we need to improve: the convenience for patients, but we also have a lot of issues in our centers with the burden of the number of patients and the lack of nursing human resources to take care of all these patients. The OBI is doing the job on behalf of the nurse, for the nurse, so that you can save nursing time.

You can save pharmacist time because you don’t have to reconstitute a syringe. The vial will be plugged in immediately, and the patient can do it on their own. Maybe the first time, or for a couple of times, you want the nurse to explain to the patients [how] do it really right, but thereafter, it can be done entirely by the patient. It’s not only at home, but it’s also going to be nurses saving time, pharmacists saving time, ultimately physicians saving time. This is where I see the real progress. It’s convenient for the patients to the utmost detail, plus for the team. The other manual push subQ formulation, they are convenient for the patient, but they don’t save time in terms of nursing time and pharmacist time. The OBI will.