Data on bispecific T-cell engagers in solid organ transplant (SOT) recipients are limited to a few case reports and small case series. No prospective trials, pooled analyses, or guideline recommendations exist, and SOT recipients have generally been excluded from the registration trials. In the cases published so far (few cases across myeloma, PTLD, ALL, and SCLC), none reported allograft rejection, and several patients had meaningful responses, some while staying on calcineurin inhibitors. Infection was the main complication reported. These are highly selected, likely publication-biased reports, so they do not establish safety.
Published experience by agent
| Agent / target | Cancer & graft | Immunosuppression | Outcome | Graft outcome | |
|---|---|---|---|---|---|
| Teclistamab (BCMA×CD3) | Relapsed/refractory myeloma (one also had AL amyloidosis/smoldering myeloma); 2 kidney recipients | Calcineurin inhibitor continued in both (tacrolimus alone in one) | Case 1: remission 9+ months. Case 2 (5 prior lines, prior belantamab): 10-month remission, infections before progression, short overall survival | No rejection | |
| Glofitamab (CD20×CD3) | Chemo-refractory Burkitt-type PTLD; simultaneous pancreas–kidney recipient | Not specified; managed jointly with the renal team | Complete metabolic response after 3 cycles, 12 cycles given, still in remission 3 months after finishing; no CRS or ICANS; parvovirus infection treated with IVIG | No clinical or lab signs of rejection | |
| Epcoritamab (CD20×CD3) | DLBCL-type PTLD | Not reported | Successful treatment (single case) | Not detailed | |
| Blinatumomab (CD19×CD3) | Pediatric B-ALL; liver recipient | Chronic immunosuppression | MRD-negative after 2 cycles, then went on to allogeneic HSCT; temporary rise in liver enzymes (bilirubin peak 2.7) | No rejection | |
| Tarlatamab (DLL3×CD3) | SCLC; liver recipient | Not reported | Marked tumor response, favorable safety | No rejection |
No reports were found of tebentafusp (gp100×CD3) or of CD3-bispecifics for other solid tumors in transplant recipients.
How bispecifics compare with other immunotherapies in SOT?
- CAR-T for PTLD: systematic reviews report allograft rejection in 14%–23.5% and graft loss in about 14%. Rejection risk is thought to rise as B cells and plasma cells recover.
- Checkpoint inhibitors: these clearly increase rejection risk. Bispecifics work differently: they redirect T cells without MHC restriction and do not broadly remove tolerance checkpoints. That is a plausible but unproven reason rejection might be less frequent.
- B-cell depletion may protect the graft: blinatumomab substantially lowered HLA antibodies in 6 of 7 B-ALL patients. In theory this could reduce antibody-mediated rejection, but that has not been shown in SOT recipients.
Keeping full immunosuppression may blunt T-cell activity, while cutting it back risks rejection. Long-term calcineurin inhibitor exposure may also cause T-cell exhaustion and shorter responses. Both teclistamab patients stayed on a calcineurin inhibitor without rejection, which suggests baseline immunosuppression may be compatible with response.
Risk from the bispecific and from transplant immunosuppression adds up. Blinatumomab has been linked to more EBV reactivation in the allogeneic HSCT setting (41.5% vs. 26.4% EBV viremia by day 100). That is worth keeping in mind for patients with EBV-associated PTLD.
At this point, data is weak and best to monitor for rejection, cancer response and infections closely if there is plans to use these in organ transplant patients.
At this point, data is weak and best to monitor for rejection, cancer response and infections closely if there is plans to use these in organ transplant patients.
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