Oncologists Debate Role of On-Body Injector for Transplant-Ineligible Myeloma

The anti-CD38 antibodies daratumumab (Darzalex) and isatuximab-irfc (Sarclisa) have been incorporated into quadruplet regimens that pair either one with bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (VRd) for patients with newly diagnosed multiple myeloma (NDMM) who are ineligible for transplant or whose transplant is deferred. Both antibodies are now available as subcutaneous (SC) injections, so route of administration no longer separates them. An on-body injector (OBI) that delivers SC isatuximab hands-free adds a new question: whether that convenience is enough to change practice for patients who are frail.

In a virtual Case-Based Roundtable event for oncologists across California and Nevada, Thomas Martin, MD, clinical research director of hematologic malignancies at the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco (UCSF), reviewed trial data for anti-CD38 regimens and SC isatuximab delivered by OBI and moderated discussion of a case patient with transplant-ineligible NDMM who is frail and lives far from his treatment center. Martin said the choice between SC daratumumab and isatuximab by OBI was one each practice would have to work out for itself.

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This article is part 1 of a 2-part series from a Case-Based Roundtable event.

CASE SUMMARY

Initial Presentation

• A 72-year-old man presented to his primary care physician.
• Fatigue, worsening back pain, unintentional weight loss
• Difficulty with daily activities, daughter says he's "slowing down"
• Comorbidities: mild chronic kidney disease, hypertension, osteoarthritis (limited mobility)
• ECOG performance status: 2
• Labs: anemia and elevated total protein
• Suspicion for malignancy
• Referred to hematology

Workup Confirms Multiple Myeloma

• Serum free light chain, lactate dehydrogenase, and β2-microglobulin: elevated
• Complete blood count: anemia present, otherwise unremarkable
• Bone marrow biopsy: 50-60% clonal plasma cells
• PET-CT: positive uptake

Clinical Profile

• International Myeloma Working Group: Frail
• Transplant ineligible NDMM

Social & Functional Context

• Lives ~45–60 min from treatment center
• Relies on daughter for transit & some support
• Prolonged clinic visits are physically taxing
• Occasional missed/rescheduled appointments due to transit and low energy

EVENT RECAP

In an opening poll, 44.4% of the 18 participating oncologists said both patients and staff strongly preferred frontline SC therapy, and only 5.6% preferred intravenous (IV) or saw barriers to SC therapy. In a second, 66.7% of 18 respondents most often selected daratumumab with VRd (D-VRd) given SC for patients ineligible for transplant or with transplant deferred, and 22.2% selected isatuximab with VRd (Isa-VRd) given IV. The NCCN guidelines list D-VRd and Isa-VRd as preferred category 1 options for patients younger than 80 years who are not frail.¹

Several participants favored a quadruplet for this 72-year-old patient. Edgardo Faylona, MD, of Optum Cancer Center in Henderson, Nevada, said, "Barring any contraindications, I always try a quadruplet regimen as much as possible." Martin said starting a quadruplet and removing the most toxic drug, or starting a doublet and adding agents, were both reasonable, and that lenalidomide dosing deserved the closest attention in a patient with mild chronic kidney disease.

Martin reviewed the phase 3 CEPHEUS trial (NCT03652064) of SC daratumumab and the phase 3 IMROZ trial (NCT03319667) of IV isatuximab, each adding an anti-CD38 antibody to VRd. At the primary analysis of CEPHEUS, minimal residual disease (MRD) negativity at 10⁻⁵, the primary end point, was 60.9% with D-VRd vs 39.4% with VRd (P < .0001), and the estimated 54-month progression-free survival (PFS) rate was 68.1% vs 49.5% (HR, 0.57; 95% CI, 0.41-0.79; P = .0005).² In IMROZ (446 patients, randomized 3:2), the 60-month PFS rate was 63.2% with Isa-VRd vs 45.2% with VRd (HR, 0.60; 98.5% CI, 0.41-0.88; P < .001), and MRD negativity was 58.1% vs 43.6% (P = .0026).³ Martin said he saw no difference in efficacy between the regimens, but the trials enrolled different populations and were not compared head-to-head, so their results cannot be compared directly.

Martin then explained the use of the isatuximab OBI, which is a single-use wearable injector that delivers a fixed 10 mL dose hands-free over about 13 to 20 minutes. The FDA approved SC isatuximab-irfc (Sarclisa Escena) on July 9, 2026, for existing isatuximab indications.⁴ In the phase 3 IRAKLIA trial (NCT05405166) in relapsed/refractory multiple myeloma (RRMM), isatuximab by OBI and IV isatuximab, each with pomalidomide (Pomalyst) and dexamethasone, produced overall response rates of 71.1% vs 70.5%, which the trial reported as noninferior, and infusion reactions occurred in 1.5% vs 25.0% of patients.⁵

In the phase 2 IZALCO trial (NCT05704049) of SC isatuximab with carfilzomib (Kyprolis) and dexamethasone in RRMM, 74.5% of 47 patients and 78.9% of 19 health care professionals preferred the OBI over manual injection at cycle 6 day 15, and no professionals preferred manual injection, in a descriptive analysis.⁶

In the only NDMM study reviewed, the single-arm phase 2 ISASOCUT trial (NCT05889221) of SC isatuximab with VRd in patients aged 65 years or older, 87.8% of 74 patients had a very good partial response or better at a median follow-up of 11.7 months.⁷

Some participants questioned what the device adds vs a manual SC injection that only takes minutes. Martin said practices treating many patients with myeloma would save nurse time, but with 1 or 2 such patients a week the savings would be small. Mark Vellek, MD, a locum tenens hematology physician in Henderson, Nevada, said, "If you had an hour or 2-hour injection, this would be incredible," but questioned adding an expensive device and a layer of complication to a short injection and asked whether low failure rates in research settings would hold in routine practice. Victoria Wang, MD, of UCSF in Palo Alto, California, said an OBI she had used left some patients unsure whether the full dose was delivered, which was hard to troubleshoot. Martin said device problems were uncommon in IRAKLIA, though the sites were experienced research centers. Ming Zhou, MD, of Gould Medical Group in Modesto, California, said the device could mainly help patients who live far away, but raised its added cost.

Others saw potential benefit from the OBI: Jahan Tavakoli, MD, of Kaiser Permanente in Greenbrae, California, said, "I'm trying to find a reason not to like it," adding that it could free chair time. Elad Neeman, MD, of Kaiser Permanente in Sebastopol, California, said chair-time use at Kaiser approaches 90%, so efficiency gains would matter, but that "eventually it boils down to value a lot of times."

In a poll, 47.1% of 17 respondents said infusion center efficiency was the greatest potential value of the OBI, 23.5% said improved patient convenience, and 23.5% saw no meaningful advantage. Martin said the patient's distance from the center made him a plausible candidate, and that the practical choice was between SC daratumumab and isatuximab by OBI. In a closing poll, 47.1% of 17 respondents anticipated that the OBI would change their practice, 35.3% were unsure, and 17.6% did not.

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_{DISCLOSURES: Martin previously reported fees for professional activities from Bristol-Myers Squibb, GlaxoSmithKline, Janssen Biotech, Inc, Pfizer, Sanofi, and Genzyme US.}

REFERENCES

1. NCCN. Clinical Practice Guidelines in Oncology. Multiple myeloma, version 5.2026. Accessed October 19, 2026. https://tinyurl.com/37vy9pm2

2. Usmani SZ, Facon T, Hungria V, et al. Daratumumab plus bortezomib, lenalidomide and dexamethasone for transplant-ineligible or transplant-deferred newly diagnosed multiple myeloma: the randomized phase 3 CEPHEUS trial. Nat Med. 2025;31(4):1195-1202. doi:10.1038/s41591-024-03485-7

3. Facon T, Dimopoulos MA, Leleu XP, et al. Isatuximab, bortezomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2024;391(17):1597-1609. doi:10.1056/NEJMoa2400712

4. FDA approves isatuximab-irfc for subcutaneous injection for multiple myeloma indications. News release. US FDA. July 10, 2026. Accessed October 20, 2026. https://tinyurl.com/4xpwfa77

5. Ailawadhi S, Špička I, Spencer A, et al. Isatuximab subcutaneous by on-body injector versus isatuximab intravenous plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma: phase III IRAKLIA study. J Clin Oncol. 2025;43(22):2527-2537. doi:10.1200/JCO-25-00744

6. Parmar G, Capra M, Hungria V, et al. Patient-reported outcomes and healthcare provider perspectives on subcutaneous isatuximab delivery via on-body injector versus manual injection: results from the phase 2 IZALCO study in relapsed/refractory multiple myeloma. Clin Lymphoma Myeloma Leuk. Published online September 3, 2026. doi:10.1016/j.clml.2026.08.019

6. Parmar G, Capra M, Seguro F, et al. Efficacy and safety of isatuximab subcutaneous plus carfilzomib and dexamethasone in patients with relapsed/refractory multiple myeloma: results of the Phase 2 study IZALCO. Blood Cancer J. 2025;16(1):16. doi:10.1038/s41408-025-01436-0

7. Bobin A, Zhang R, Morisse M, et al. Multicenter phase 2 study of subcutaneous isatuximab plus bortezomib, lenalidomide and dexamethasone (Isa Sc-VRd) in transplant ineligible newly diagnosed multiple myeloma: Final analysis of the ISASOCUT study (IFM 2022-05). Blood. 2025; 146 (Supplement 1): 2275. doi:10.1182/blood-2025-2275