ISATUXIMAB PLUS POMALIDOMIDE-DEXAMETHASONE IN RELAPSED/REFRACTORY MULTIPLE MYELOMA: SUBGROUP ANALYSIS BY PRIOR ANTI-CD38 EXPOSURE FROM THE PHASE 3 IRAKLIA TRIAL

@article{oriol2026isatuximab,
  title = {{ISATUXIMAB PLUS POMALIDOMIDE-DEXAMETHASONE IN RELAPSED/REFRACTORY MULTIPLE MYELOMA: SUBGROUP ANALYSIS BY PRIOR ANTI-CD38 EXPOSURE FROM THE PHASE 3 IRAKLIA TRIAL}},
  author = {Albert ORIOL and Marek HUS and Raimundo GAZITUA and Aijun LIAO and Wojt JANOWSKI and Cindy Huey-shin LEE and Gabor MIKALA and Artur JURCZYSZYN and Alejandro BERKOVITS and Jin LU and Fredrik SCHJESVOLD and Silvia LING and Andrew SPENCER and Sikander AILAWADHI and Tondre T. BUCK and Umer KHAN and Florence SUZAN and Maya Stefanova- URENA and Vania HUNGRIA and Ivan ŠPIčKA},
  journal = {Hematology, Transfusion and Cell Therapy},
  year = {2026},
  month = oct,
  doi = {10.1016/j.htct.2026.107882},
  url = {https://doi.org/10.1016/j.htct.2026.107882},
  note = {CC BY},
}

TY  - JOUR
TI  - ISATUXIMAB PLUS POMALIDOMIDE-DEXAMETHASONE IN RELAPSED/REFRACTORY MULTIPLE MYELOMA: SUBGROUP ANALYSIS BY PRIOR ANTI-CD38 EXPOSURE FROM THE PHASE 3 IRAKLIA TRIAL
AU  - Albert ORIOL
AU  - Marek HUS
AU  - Raimundo GAZITUA
AU  - Aijun LIAO
AU  - Wojt JANOWSKI
AU  - Cindy Huey-shin LEE
AU  - Gabor MIKALA
AU  - Artur JURCZYSZYN
AU  - Alejandro BERKOVITS
AU  - Jin LU
AU  - Fredrik SCHJESVOLD
AU  - Silvia LING
AU  - Andrew SPENCER
AU  - Sikander AILAWADHI
AU  - Tondre T. BUCK
AU  - Umer KHAN
AU  - Florence SUZAN
AU  - Maya Stefanova- URENA
AU  - Vania HUNGRIA
AU  - Ivan ŠPIčKA
PY  - 2026
DA  - 2026/10/23
JO  - Hematology, Transfusion and Cell Therapy
DO  - 10.1016/j.htct.2026.107882
UR  - https://doi.org/10.1016/j.htct.2026.107882
AB  - Background: With the growing use of anti-CD38 therapies in early multiple myeloma (MM) management, there is a need for data in patients previously exposed to anti-CD38 therapy to guide decision making. In the Phase 3 IRAKLIA trial (NCT05405166), patients with relapsed/refractory MM (RRMM) received the anti-CD38 monoclonal antibody isatuximab (Isa) subcutaneously (SC) delivered via an innovative on-body injector (OBI) or intravenously (IV), with pomalidomide and dexamethasone (Pd). In this post hoc analysis, we examined outcomes in IRAKLIA patients with vs without prior anti-CD38 exposure. Methods: RRMM patients ≥18 years with ≥1 prior line of therapy including lenalidomide and a proteasome inhibitor were randomized to receive Isa SC (n=263) or IV (n=268) weekly in Cycle 1, then every 2 weeks, with Pd. Patients with prior anti-CD38 exposure <9 months (mos) before randomization or intolerance to anti-CD38 were excluded. Refractory patients were defined as those who failed to achieve minimal response on treatment or had progression within 60 days after last dose. Patients receiving Isa SC or IV were pooled. Results: Overall, 67 patients (12.6%) had prior anti-CD38 exposure with a median washout period of 20.2 mos, of which 26 (38.8%) were anti-CD38 refractory. Baseline characteristics were largely consistent between patients with or without prior anti-CD38 exposure; the median follow-up for the overall population was 12 mos. Patients with prior anti-CD38 exposure had an overall response rate (ORR) of 52.2%, 12-mo progression-free survival (PFS) rate of 40.6%, and median PFS of 8.5 mos. In patients without prior exposure, an ORR of 73.5%, 12-mo PFS of 68.8%, and non-estimable (NE) median PFS were reported. Anti-CD38 non-refractory vs refractory patients had an ORR of 48.8% vs 57.7%, 12-mo PFS of 38.9% vs 42.2%, and median PFS of 9.0 vs 7.5 mos. Patients with a longer washout period (>median of 20.2 mos) had an ORR of 63.6%, 12-mo PFS of 61.8% and NE median PFS, whereas patients whose prior anti-CD38 therapy ended more recently (≤median of 20.2 mos) had an ORR of 41.2%, 12-mo PFS of 19.2%, and median PFS of 6.7 mos. The safety profile of Isa + Pd was similar in patients with vs without prior anti-CD38 exposure. Conclusions: Isa + Pd demonstrated clinical benefit across anti-CD38–naïve, anti-CD38–exposed, and anti-CD38–refractory patients. A washout period >median of 20.2 mos resulted in outcomes comparable to those in anti-CD38–naïve patients, and outcomes were consistent between anti-CD38–exposed and anti-CD38–refractory patients after a > 9-mo washout period. Efficacy of Isa + Pd in patients with prior anti-CD38 exposure from the IRAKLIA trial presents an opportunity to address an unmet need in a difficult-to-treat patient population.
SN  - 2531-1379
SN  - 2531-1387
ER  -