Over the past few decades, advances in the treatment of multiple myeloma (MM) have accelerated at a thrilling pace, with a wealth of new therapeutic options now available for patients with this serious disease. The development of immunotherapies has revolutionized the treatment paradigm for MM, including the use of highly targeted and better-tolerated therapies.
Our team at UC San Francisco’s Hematology, Blood and Marrow Transplant, and Cellular Therapy (HBC) Program has been leading the development of two of the most exciting of these novel therapies, helping to bring these treatments into clinical practice. They include chimeric antigen receptor T cells (CAR-T) and T-cell engagers (TCE); both involve directing cytotoxic T cells to an MM-specific antigen but differ in their preparation, mode of delivery, and side-effect profile.
Two recent UCSF patient cases – described below – highlight how these immunotherapies are helping MM patients who may have given up hope.
CAR-T therapy for relapsed and refractory MM results in patient’s complete response; study leads to FDA approval
In 2018, after failing nearly all Food and Drug Administration (FDA)-approved myeloma therapies, an MM patient in her 50s was enrolled in the Celgene phase II study of bb2121, an anti-B-cell maturation antigen (BCMA) CAR-T therapy. Led by UCSF’s Nina Shah, MD, a hematologist-oncologist and MM researcher, the study investigated the use of this treatment for relapsed and refractory MM. Despite having steadily rising paraproteins and a significant burden of disease, with over 80 percent bone marrow involvement at study enrollment, the patient developed a profound response to therapy, with complete resolution of her paraprotein and no evidence of disease on bone marrow evaluation, all without significant side effects. Impressively, she remains disease-free today, three years later, in a minimal residual disease (MRD)-negative stringent complete response and has been off treatment since her CAR-T therapy.
Based on the phenomenal results of this patient and others at UCSF as well as across the country, bb2121 – now known as idecabtagene vicleucel and by the trade name Abecma – was approved by the FDA in March 2021.
Therapy shows greater results and tolerance in elderly patient
In another case, an MM patient in his 80s was developing progressive disease with rising light chain levels after more than five prior lines of therapy. After being either resistant or intolerant to the majority of available MM treatment options, he was enrolled in one of the program’s ongoing BCMA-targeted TCE clinical trials, also directed by Dr. Shah. Remarkably, after only one cycle, the patient developed a greater than 99 percent reduction in his kappa free light chains, consistent with a complete response. He currently remains on treatment, tolerating therapy without significant side effects. The case demonstrates that these immunotherapies are not only very effective, but can also be well tolerated, even for elderly patients and those with intolerances to prior therapies.
These clinical trials are proving to be game changers for many patients whose multiple myeloma has been resistant to treatment, or who have not tolerated available therapies. To accomplish both goals is really a double triumph for disease management.
Additional promising research underway
Our team is leading many exciting clinical trials that are currently open for enrollment for patients with multiple myeloma, including nine clinical trials in the realm of immunotherapy utilizing CAR-T or TCE technologies. Furthermore, through generous donations from the UCSF Stephen and Nancy Grand Multiple Myeloma Translational Initiative, our team has been developing new drug targets, optimizing immunotherapy design and building a homegrown CAR-T program. This work promises to bring even more effective treatment options to patients across the globe.
Authors:
Assistant Professor, Hematology and Blood and Marrow Transplant
Assistant Professor, Hematology and Blood and Marrow Transplant
For more information:
Hematology, Blood & Marrow Transplant, and Cellular Therapy Program
General: (415) 353-2421 | New Referrals: (415) 353-2051 | Fax: (415) 353-2467
View multiple myeloma clinical trials open to enrollment at UCSF
