At ASH 2019 in Orlando, Dr. John Pagel of Swedish Hospital in Seattle and a member of the board of directors of the CLL Society, interviewed Dr. Stephen Schuster, the Robert and Margarita Louis-Dreyfus Professor in Chronic Lymphocytic Leukemia and Lymphoma Clinical Care and Research at the Univ. of Pennsylvania.
Dr. Schuster gave one of the prestigious plenary talks at the ASH Annual Meeting. As a reminder, the plenary talk is reserved for those talks deemed so game-changing that there are no other competing sessions scheduled at the same time so that all might attend.
Dr. Schuster spoke about the powerful results in a phase 1 trial of mosunetuzumab, a bispecific antibody.
To learn more about bispecific antibodies, see this accompanying article.
- Treatments are needed for “Poor Prognosis Non-Hodgkin Lymphoma Patients, Including Those Who Are Resistant to or Relapsing After Chimeric Antigen Receptor T-Cell (CAR-T) Therapies”
- CLL is one type of Non-Hodgkin Lymphoma (NHL) and while this time, the trial did not include any chronic lymphocytic leukemia patients, future reports surely will.
- Mosunetuzumab is a bispecific antibody that attaches both to the CD20 marker found on normal B cells and CLL cells and at the same time to CD3 that is found on T cells.
- When these two cells are pulled close together by mosunetuzumab, the T cells proliferate and start destroying the CD20+ cells, including the cancerous clonal cells.
- In this very difficult to treat group of patients who failed CAR-T therapy, this early-stage trial found an overall response rate (ORR) and complete response (CR) rates of 43.8% (7/16) and 25.0% (4/16, 2 diffuse large B-cell lymphoma and 2 follicular lymphoma), respectively.
- ORR and CR rates were 64.1% (41/64) and 42.2% (27/64) in indolent NHL patients and 34.7% (41/119) and 18.6% (22/119) in aggressive NHL patients, respectively.
- Cytokine release syndrome (CRS) was observed in 28.4%. David Porter, also of UPenn, explains CRS in relationship to CAR-T in this video.
- There are several advantages of bispecific antibodies as they are “off the shelf” and not bespoke for each patient.
While it would be great to see 100% of patients reach a complete remission, these are impressive results for this very difficult population that was running out of options.
This type of therapy with bispecific antibodies is just beginning to be researched in CLL, but we believe it is an important new direction in immunotherapy that could play a significant role in future treatment protocols.
At the CLL Society, we are eager for our readers to be aware not only of what’s happening in CLL therapy now but also a little of the history about how we got here and even more importantly, where we might be going next.
We are now producing a series of articles on various aspects of immunotherapy.
We are also expanding our interview team. Expect to see more of your favorite CLL doctors interviewing other favorites at future blood cancer conferences.
Here is Dr. Pagel’s interview with Dr. Schuster.
Here is his plenary abstract: Mosunetuzumab Induces Complete Remissions in Poor Prognosis Non-Hodgkin Lymphoma Patients, Including Those Who Are Resistant to or Relapsing After Chimeric Antigen Receptor T-Cell (CAR-T) Therapies, and Is Active in Treatment through Multiple Lines.
Stay strong, we are all in this together.
Brian Koffman, MDCM (retired)
EVP and CMO, CLL Society
Dr. Brian Koffman, a well-known retired doctor, educator, and clinical professor turned patient has dedicated himself to teaching and helping the CLL community since his diagnosis in 2005. He serves as the Executive Vice President and Chief Medical Officer of the CLL Society Inc.
Originally published in The CLL Society Tribune Q2 2020.