Fast Track Designation and Labeling Updates: The Latest FDA Actions in Hematology Oncology

Recent regulatory actions from the FDA, including new drug application (NDA) acceptances and labeling updates, introduce new clinical considerations for oncology nurses and advanced practice providers (APPs) managing relapsed or refractory (R/R) hematologic malignancies.

Trispecific Antibody Earns Fast Track Designation in R/R Multiple Myeloma

The FDA has granted fast track designation (FTD) to IBI3003, an investigational anti-GPRC5D/BCMA/CD3 trispecific antibody.¹ This designation applies specifically to the treatment of relapsed/refractory (R/R) multiple myeloma in patients who have received 4 or more prior lines of therapy, including a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 monoclonal antibody. IBI3003 is designed to target both GPRC5D and BCMA to inhibit the tumor escape often associated with single-antigen targeting.

Clinical data from a phase 1/2 trial involving 39 patients demonstrated an overall response rate (ORR) of 83.3% at doses of 120 μg/kg or higher. Notably, an 80% ORR was observed in patients with extramedullary disease, and a 77.8% ORR was recorded among patients with prior exposure to BCMA- or GPRC5D-directed therapies.

For patients achieving a complete response or better, the minimal residual disease (MRD) negativity rate was 100%. From a safety perspective, cytokine release syndrome (CRS) events were limited to grade 1 to 2, and only 2 cases of grade 1 to 2 immune effector cell-associated neurotoxicity syndrome (ICANS) were reported. Common treatment-emergent adverse events (TEAEs) related to GPRC5D targeting included grade 1 to 2 effects on the skin, nails, and oral cavity.

FDA Accepts New Drug Application for Iberdomide in R/R Multiple Myeloma

The FDA has accepted the NDA for iberdomide used in combination with daratumumab (Darzalex) and dexamethasone (IberDd) for patients with R/R multiple myeloma. ²This application has been granted priority review and breakthrough therapy designation, with a target action date of August 17, 2026. Iberdomide is a potential first-in-class cereblon E3 ligase modulator (CELMoD) agent. Iberdomide uses targeted protein degradation (TPD) to address therapeutically relevant proteins that were previously considered “undruggable.”

The regulatory filing is supported by the phase 3 EXCALIBER-RRMM study (NCT04975997), which compares the oral IberDd regimen against the standard triplet of daratumumab, bortezomib (Velcade), and dexamethasone (DVd). The study utilizes dual primary endpoints of MRD negativity and progression-free survival (PFS).

Using next-generation sequencing and flow cytometry, clinicians can now identify a single malignant cell among 100,000 to 1,000,000 normal cells. MRD negativity is increasingly recognized by regulatory authorities as a predictor for improved survival and longer remission.

Axi-Cel Labeling Update Accepted by FDA for R/R PCNSL

The FDA has approved a label update for the CAR T-cell therapy axicabtagene ciloleucel (Yescarta; axi-cel), removing previous limitations of use for patients with R/R primary central nervous system lymphoma (PCNSL).³ PCNSL is an aggressive form of non-Hodgkin lymphoma originating in the brain, spinal cord, eye, or cerebrospinal fluid. The prognosis for this condition is generally poor, with a 5-year survival rate of approximately 30%.

The label update was supported by a phase 1 investigator-sponsored study conducted by the Dana-Farber Cancer Institute. Safety data from this trial showed that neurologic toxicities occurred in 85% of patients (11/13), with 31% experiencing grade 3 events. Common neurologic AEs included confusional states (38%), headaches (31%), somnolence (31%), disturbance in attention (23%), lethargy (23%), tremor (23%), gait disturbance (15%) hypersomnia (15%), insomnia (15%), and seizures (15%). The median time to the onset of neurologic toxicity was 3 days, while the median time to the first grade 3 or higher event was 9.5 days.

Oncology nurses and APPs should remain vigilant regarding the boxed warnings for axi-cel, which include CRS, neurologic toxicities, and secondary hematological malignancies. CRS has occurred in 90% of patients across non-Hodgkin lymphoma trials, characterized by fever, hypotension, tachycardia, and hypoxia. Management protocols require ensuring 2 doses of tocilizumab are available prior to infusion and monitoring patients daily for at least 7 days following the procedure. Patients should also be monitored for serious infections, which occurred in 45% of patients in clinical studies. Due to the risk of ICANS, patients are advised to avoid driving for at least 8 weeks post-infusion.

References

1. Innovent Announces IBI3003 (GPRC5D/BCMA/CD3 Trispecific Antibody) Receives Fast Track Designation from the U.S. FDA for Relapsed or Refractory Multiple Myeloma. Innovent Biologics. News release. January 26, 2026. Accessed February 18, 2026. https://www.prnewswire.com/news-releases/innovent-announces-ibi3003-gprc5dbcmacd3-trispecific-antibody-receives-fast-track-designation-from-the-us-fda-for-relapsed-or-refractory-multiple-myeloma-302669853.html
2. U.S. Food and Drug Administration Accepts Bristol Myers Squibb's New Drug Application for Iberdomide in Patients with Relapsed or Refractory Multiple Myeloma. Bristol Myers Squibb. News release. February 17, 2026. Accessed February 18, 2026. https://news.bms.com/news/corporate-financial/2026/U-S--Food-and-Drug-Administration-Accepts-Bristol-Myers-Squibbs-New-Drug-Application-for-Iberdomide-in-Patients-with-Relapsed-or-Refractory-Multiple-Myeloma/default.aspx
3. FDA Approves Label Update for Kite’s Yescarta® for Relapsed/Refractory Primary Central Nervous System Lymphoma. Kite Oncology. News release. February 6, 2026. Accessed February 18, 2026. https://www.kitepharma.com/news/press-releases/2026/2/fda-approves-label-update-for-kites-yescarta-for-relapsedrefractory-primary-central-nervous-system-lymphoma