Oncology News Central (ONC)FDA Delivers Second Rejection to CAR-T for Posttransplant Lymphoproliferative Disorder

The FDA reversed its approval stance on CAR-T therapy for a rare post-transplant cancer, contradicting 5+ years of guidance after manufacturer fixed all cited deficiencies. Second rejection now claims the single-arm ALLELE trial is insufficient despite the agency previously accepting this exact study design for an orphan disease affecting high-mortality transplant patients.

⚖️ PROFESSIONAL IMPACT

• FDA reversed position on study adequacy after manufacturer completed remediation, creating regulatory uncertainty for orphan disease trials previously approved under breakthrough designation
• Agency rejected same trial design it had accepted through multiple regulatory interactions, undermining precedent for single-arm studies in rare conditions with no standard therapy
• New clinical review team raised concerns contradicting prior guidance, suggesting regulatory instability when reviewer assignments change during application process
• Breakthrough designation and orphan drug status provided no protection from shifting evidentiary standards, weakening predictive value of these regulatory pathways

🎯 ACTION ITEMS

• Document that breakthrough/orphan designations don’t guarantee approval pathway stability for trial design discussions
• Review current patients on compassionate use programs—regulatory limbo may affect access timelines
• Monitor Pierre Fabre’s FDA meeting outcomes to assess precedent for EBV+ PTLD treatment landscape
• Update transplant teams that no approved therapy exists despite previously promising regulatory trajectory

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