DLI Therapy Using T-Rapa Cells: Graft-Versus-Lymphoma and GvHD Effects

Abstract

DLI therapy has limited efficacy and substantial GVHD risks. IL-4 polarized, rapamycin-resistant CD4+ (T-Rapa) cells were safe when administered as pre-emptive DLI (Fowler, Blood, 2013). Here, we evaluated the clinical GVL and GVHD effects of T-Rapa DLI for disease relapse or progression. Patients with progressive or relapsed hematologic malignancy after reduced-intensity, HLA-matched sibling transplant were treated with donor T-Rapa cells (target dose: 2.5 x 107 cells/kg; 6-day manufacturing method using anti-CD3/CD28, IL-4, IL-2, and rapamycin). 13 patients with NHL, HD, or CLL were treated (Table 1). Each patient had measurable disease by CT scan, some with bulky relapse (n=4). 6 patients received multiple T-Rapa DLI; 12 received conditioning prior to DLI. 8 patients had acute GVHD and 5 had chronic GVHD prior to DLI. After T-Rapa DLI therapy, acute and chronic GVHD status worsened in 1/13 and 4/13 patients, respectively. Overall response rate was 4/13 (DLBCL-DH [n=2]; NHL-GZ; CLL), with 2 patients each having partial or complete response. Patient deaths were related to PD (n=6), GVHD (n=1), and infection (n=1). T-Rapa cell DLI products can mediate GVL effects in NHL, including against double-hit and gray zone lymphoma. Because T-Rapa cell GVL effects occurred with modest exacerbation of GVHD, further studies will evaluate this novel DLI therapy.Table 1T-Rapa DLI Therapy: GVL and GVHD EffectsAge GenderDiagnosisTime to DLI (post-SCT) (davs)Bulky DiseasePrior GVHDChronic (grade) (Y/N)T-R. pa DLI # Prep. (Y/N)bGvHD OutcomeGVT Outcome (Best Response)Survival (post-DLI) (days; current disease status)Acute (Y/N)55MCLL2358Y0Y1YNo incrPDDead (337; Infection)31FHD1710NIIY1YNo incrPDDead (282; PD)58MNHL, PDC1014NIIN3YNonePDDead (725; PD)48MDLBCL, DH490N0Y2YIncr ChronicCRAlive (+798; PR)46MDLBCL, DH525NIIN3YNew Onset ChronicCRAlive (+720; CR)23MHD454YIIN3YNonePDDead (540; PD)42MNHL. GZ310NIIN2YNonePDDead (59; PD)30FHD, EBV, PTLD217N0N1NNonePDDead (28; PD)17FNHL. GZ66NIIY1YIncr ChronicCRAlive (+613; SD)57MCLL1204NIIN1YIncr AcuteCRDead (150; GVHD)46FDLBCL143NIIY1YIncr ChronicPRAlive (+493; CR)53MDLBCL, DH253Y0N2YNonePDAlive (+377; SD)36MHD125Y0N1YNonePDDead (54; PD)aPDC, plasmacytoid dendritic cell; DH, double-lit; GZ=gray zone; bwithin 2 weeks of DLI. Open table in a new tab