Breakthoughs: Powerful Two-Pronged Therapy Against Multiple Myeloma

City of Hope — Developing Bispecific Antibody Therapies to Improve Multiple Myeloma Treatment

By pinpointing genetic vulnerabilities in cancer cells and harnessing the power of the immune system to attack those cells, City of Hope is advancing novel immunotherapeutic modalities like bispecific antibody treatment to defeat multiple myeloma. Unlike standard antibody drugs, bispecific antibodies are uniquely engineered to bind to both cancer cells and T cells, engaging T cells to target and destroy cancer cells while minimizing side effects.

Groundbreaking Research and Advancements in Immunotherapy

Amrita Krishnan, M.D.
Amrita Krishnan, M.D.

Amrita Krishnan, M.D., director of the Judy and Bernard Briskin Center for Multiple Myeloma Research at City of Hope, is currently involved in groundbreaking research to investigate three promising new bispecific antibodies for use in relapsed or refractory multiple myeloma.

Teclistamab in combination therapy for relapsed/refractory multiple myeloma

Teclistamab, a bispecific antibody recently approved by the Food and Drug Administration for multiple myeloma, targets the B cell maturation antigen, which is heavily present on myeloma cells and only minimally present on other cells, and is currently being used in patients with relapsed disease who have tried four or more other treatments without success. Krishnan collaborated in a Phase 3 trial combining teclistamab with other drugs for earlier relapses of myeloma.

This Phase 3 trial, led by principal investigator Murali Janakiram, M.D., M.S., associate professor, Division of Multiple Myeloma, Department of Hematology & Hematopoietic Cell Transplantation, is ongoing and recruitment is still open. Patient enrollment qualifications include:

murali-janakiram
Murali Janakiram, M.D., M.S.
  • Documented multiple myeloma as defined by the criteria: a) multiple myeloma diagnosis according to the International Myeloma Working Group (IMWG) diagnostic criteria, b) measurable disease at screening as defined by any of the following: 1) serum M-protein level ≥ 0.5 gram per deciliter (g/dL), or 2) urine M-protein level ≥200 milligrams (mg)/24 hours; or 3) serum immunoglobulin free light chain ≥ 10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio
  • Received one to three prior line(s) of antimyeloma therapy, including a proteasome inhibitor (PI) and lenalidomide; participants who have received only one line of prior antimyeloma therapy must be lenalidomide refractory. Stable disease or progression on or within 60 days of the last dose of lenalidomide given as maintenance will meet this criterion.
  • Documented evidence of progressive disease based on investigator's determination of response by IMWG criteria on or after their last regimen
  • An eastern cooperative oncology group (ECOG) performance status score of 0, 1 or 2 at screening and prior to the start of administration of study treatment
  • Clinical laboratory values within the specified range

Read more about the clinical study here:

Safety and tolerability of Teclistamab for relapsed/refractory multiple myeloma

Krishnan is involved in another clinical trial for teclistamab designed to evaluate its use in patients with relapsed or refractory multiple myeloma. The purpose of this Phase 1, open-label dose escalation study is to identify the recommended Phase 2 dose(s) and schedule for teclistamab and evaluate safety, tolerability, pharmacokinetics and preliminary anti-tumor activity at that dose.

This trial is ongoing and recruitment is open. Patient enrollment qualifications include:

  • Documented diagnosis of multiple myeloma according to IMWG diagnostic criteria
  • Measurable multiple myeloma that is relapsed or refractory to established therapies with known clinical benefit in relapsed/refractory multiple myeloma or intolerant of those established multiple myeloma therapies, and a candidate for teclistamab treatment in the opinion of the treating physician. Prior lines of therapy must include a proteasome inhibitor, an immunomodulatory drug and an anti-CD38 monoclonal antibody in any order during the course of treatment. Participants who could not tolerate a proteasome inhibitor or immunomodulatory drugs and an anti-CD38 monoclonal antibody are allowed.
  • ECOG Performance Status score of 0 or 1
  • Female participants of childbearing potential must use acceptable method of contraception.
  • Participants must sign an ICF prior to the initiation of any study-related tests or procedures indicating that he or she understands the purpose of the study and is willing to participate in the required procedures.

Read more about the clinical study here:

Talquetamab therapy for relapsed/refractory multiple myeloma

Krishnan is also collaborating in a clinical trial for talquetamab, an off-the-shelf bispecific antibody that targets a protein called GPRC5D, which represents a new approach for destroying multiple myeloma cells. It was granted a Breakthrough Therapy Designation in 2022, which helps expedite the development and regulatory review of promising investigational medicines. If approved by the Food and Drug Administration, talquetamab would give patients who have exhausted all their options yet another chance to prolong their lives, says Krishnan.

“The responses to talquetamab tend to be rapid, and the responses also tend to be deep,” says Krishnan. “And we are starting to see durable responses. All that is very encouraging. It's very exciting to have many more options for our patients.”

This trial is ongoing and recruitment is still open. Patient enrollment qualifications include:

  • Documented initial diagnosis of relapsed or refractory multiple myeloma according to IMWG diagnostic criteria
  • Part 3: Measurable disease cohort A, cohort B, and cohort C: Multiple myeloma must be measurable by central laboratory assessment.
  • ECOG performance status score of 0 to 2
  • Women of childbearing potential must have a negative pregnancy test at screening and prior to the first dose of study drug using a highly sensitive pregnancy test either serum (beta human chorionic gonadotropin [hCG]) or urine.
  • Willing and able to adhere to the prohibitions and restrictions specified in this protocol

Read more about the clinical study here:

City of Hope Is One of the Nation’s Top 10 “Best Hospitals” for Cancer Care and the Premier Choice for Multiple Myeloma Treatment

City of Hope received an “exceptional” rating by the National Cancer Institute (NCI)—the highest rating possible for a U.S. cancer center — putting the center in the top echelon of the nation’s 53 NCI-designated comprehensive cancer centers. As a leader in providing world-class care and unparalleled outcomes for various malignancies, City of Hope is one of few national centers with a multidisciplinary team specializing in the treatment of myeloma and multiple myeloma and has one of the highest volumes of patients with these cancers in Southern California.

City of Hope is one of seven centers comprising the Hematologic Malignancies Research Institute. Thanks to the generous gift from the Briskin Family Foundation, City of Hope’s Judy and Bernard Briskin Center for Multiple Myeloma Research is the only Southern California member of the Multiple Myeloma Research Consortium, a partnership of some 22 facilities across the country dedicated to rapidly bringing the most promising new treatments to patients. By integrating across multiple expertise domains, our collaborative team continues to advance care through groundbreaking research and dedication to addressing the concerns of each patient.

To refer a patient, visit CityofHope.org/patients/refer-a-patient, or call

800-264-4377 to speak with a patient referral specialist.

To refer a patient to a clinical trial, visit https://www.cityofhope.org/clinical-trials or call

877-467-3411.

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