Phase 1 Orca-Q naïve T-cell–depleted allogeneic HSCT to reduce GVHD in high-risk myeloma

This Phase 1 interventional study at UC Davis evaluates ORCA-Q allogeneic hematopoietic stem cell transplantation as a potentially safer, immune-engineered way to deliver graft-versus-myeloma activity in relapsed/refractory (R/R) high-risk multiple myeloma. ORCA-Q (from Orca Bio) is a precision-selected donor graft that depletes naïve T lymphocytes—a T-cell subset thought to contribute to graft-versus-host disease (GVHD)—while retaining other immune/stem cell components intended to support engraftment, infection control, and anti-tumor effects. Participants receive myeloablative conditioning chemotherapy—thiotepa (DNA-alkylating agent), busulfan (DNA-alkylating agent), and fludarabine (purine analog/DNA synthesis inhibitor)—followed by ORCA-Q “prime” and “supplement” infusions. The eligible population is patients with R/R high-risk MM who are already in at least a partial or complete response (often with MRD assessment), essentially testing whether a lower-GVHD allogeneic platform can consolidate deep remissions. Today’s care for R/R high-risk MM is sequential novel-agent therapy (proteasome inhibitors, IMiDs, anti-CD38 antibodies), often followed by BCMA- or GPRC5D-targeted cellular therapy or bispecific antibodies in later lines; allogeneic transplant is used selectively due to toxicity/GVHD risk, and this trial’s core angle is whether engineered graft composition can change that risk–benefit calculus.