Dr Callander on Ongoing and Future Clinical Trials in Multiple Myeloma at Carbone Cancer Center

Natalie S. Callander, MD, associate professor, Division of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, director, University of Wisconsin Carbone Cancer Center Myeloma Clinical Program, discusses ongoing and planned clinical trials evaluating the use of novel therapeutic regimens in multiple myeloma.

The single-arm, multicenter, phase 2 BMTCTN1902 trial (NCT05032820) is investigating the use of anti-BCMA CAR T-cell therapy (bb2121) for patients with multiple myeloma whose disease has had a suboptimal response to autologous stem cell transplantation (ASCT) followed by 1 year of maintenance lenalidomide (Revlimid), Callander begins. It is hypothesized that CAR T-cell therapy will upgrade patient responses, Callander states. Responses are deemed suboptimal if they are less than a complete response (CR) after 3 months of maintenance therapy, she notes. The study's primary outcome is the efficacy of BCMA CAR-T cell therapy, which is defined as the patient having a response of CR or better by the 6-month time point following treatment.

Additionally, the registrational phase 2 iMMagine-1 trial (NCT05396885) is investigating the use of a novel CAR T-cell asset, CART-ddBCMA for patients with relapsed/refractory multiple myeloma in later lines, Callander says. Unlike standard CAR T-cell therapies, this agent is designed with a novel synthetic, animal variant region rather than a single-chain variant region. This different binding domain may make the combination less immunogenic, Callander explains. The trial has begun enrollment.

Future avenues for research at Carbone Cancer Center include the planned investigation of a triplet combination comprised of carfilzomib (Kyprolis), isatuximab-irfc (Sarclisa), selinexor (Xpovio), and dexamethasone, Callander continues.

Data from the phase 2 MASTER-2 trial (NCT03224507) showed the viability of quadruplet consolidation regimens with carfilzomib in this population. The minimal residual disease (MRD)–guided trial evaluated a combination of daratumumab (Darzalex), lenalidomide, carfilzomib and dexamethasone (KRd) in patients with newly diagnosed multiple myeloma who had undergone autologous hematopoietic cell transplantation, Callander reports. There is also interest in investigating the use of an iberdomide-containing consolidation maintenance therapy to improve response rates after ASCT, Callander concludes.