Relapsed/Refractory Multiple Myeloma Treatment Advances With Three BiTE Therapy Options

By the end of 2023, there were 3 bispecific T-cell engagers (BiTEs) that had been FDA-approved for the treatment of relapsed/refractory (R/R) multiple myeloma (MM), explained Brooke Adams, PharmD, BCOP, clinical pharmacy specialist, malignant hematology/bone marrow transplant/cellular therapy, Orlando Health Cancer Institute, during a presentation at the Hematology/Oncology Pharmacy Association (HOPA) Annual Conference 2024 in Tampa, Florida. These agents include teclistamab-cqyv (Tecvayli; Janssen Biotech), which was approved on October 25, 2022; talquetamab-tgvs (Talvey; Janssen Biotech), approved on August 9, 2023; and elranatamab-bcmm (Elrexfio; Pfizer), approved on August 14, 2023. Each of these agents was granted accelerated approval by the FDA for treatment of adults with R/R MM who have received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

Adams explained further that although MM is a rare malignancy and only accounts for 1.8% of new cancer cases, it accounts for 18% of hematologic malignancies. For this reason, patients with MM may encompass a significant portion of the patient population.

“In regard to background, we know that [MM] is a rare malignancy. It's not breast cancer, it's not lung cancer, but it does encompass a large patient population that we do see every day,” Adams said during the HOPA session. “It's also twice as common in our African American patient population, and males do get it more frequently, with the median age of diagnosis at 69 years. So, it is a diagnosis of the elderly, depending on who you talk to. The median age of death is 75 years.”

Additionally, Adams noted that over the past 10 years, research into MM treatment has advanced significantly, especially in relation to the 5-year relative survival rate.

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“I remember the 5-year relative survival rate when I was in residency, and it was not 60%,” Adams said during the session. “We've done a great job, and we're just going to continue to do even better as time goes on.”

However, despite these advances, Adams noted that MM is still incurable. Currently, MM is a chronic disease state for patients with this diagnosis.

“We keep them in remission as long as we can,” Adams said. “Ultimately, they do relapse. They're going to continue to relapse throughout their lifetime, and you'll see the tumor burden as it continues to rise and go down and rise and go down throughout their lifetime.”

Both teclistamab-cqyv and elranatamab-bcmm target B-cell maturation antigen (BCMA), whereas talquetamab-tgvs binds to GPRC5D, according to Adams.

“GPRC5D is a novel target for 2 brand new first-in-class drugs that we have, but [looking at] everywhere else [GPRC5D] is expressed—it is expressed in the lungs, on the nails, in the mouth, and on hair,” Adams said during the session. “Keep this in mind whenever we talk about the novel toxicities of these drugs.”

The efficacy of teclistamab-cqyv was assessed in the open-label phase 1/2 single-arm MajesTEC-1 study (NCT03145181 [phase 1] and NCT04557098 [phase 2]). The primary end point was overall response rate (ORR), which was reported as 63%, Adams explained. Secondary efficacy end points included median time to first response at 1.2 months, and best response at 3.8 months. Additionally, median duration of response (DOR) was 18.4 months (95% CI, 14.9 - NE), maintenance of response was 12 months or greater at 68.5% (95% CI, 55.7 – 77.1), median duration of progression-free survival (PFS) was 11.3 months (95% CI, 8.8 – 17.1), and median duration of overall survival (OS) was 18.3 months (95% CI, 15.1 - NE).

“With ORR of 63%, these responses were very good, with complete remission or better,” Adams said during the session. “It had a median duration of [PFS] of almost a year, and the duration of [OS] was a year and a half. So, these are outstanding numbers that we haven't seen in [MM] for an off-the-shelf therapy.”

In the MagnetisMM-3 study (NCT04649359), elranatamab-bcmm was evaluated in patients with R/R MM. The primary end point was ORR, which was reported as 61%, with a median follow up of 10.4 months and an 84% probability of maintaining response at 9 months. The probability of PFS and OS were also reported to be 63% and 70%, respectively, at 9 months. However, median DOR was not reached.

In the phase 1/2 MonumenTAL-1 study (NCT03399799 [phase 1], NCT04634552 [phase 2]), investigators assessed the efficacy of talquetamab-tgvs in patients with R/R MM. The primary efficacy outcome measures were ORR and DOR, and results were stratified by the weekly and every-2-week dosing regimens. In the weekly cohort, the median duration of follow-up from first response was 13.8 months (range, 0.8-15.4 months), while the median duration for the biweekly schedule was 5.9 months (range, 0-9.5 months), with 85% of participants maintaining response for at least 9 months. Additionally, median time to first response for the weekly and biweekly groups was 1.2 months (range, 0.2-10.9 months) and 1.3 months (range, 0.2-9.2 months), respectively. The ORR was 73%.

“All 3 of our BiTEs [for R/R MM] have outstanding response rates from 60% to 70%, even in that heavily pretreated patient population,” Adams said during the session. “Major adverse events, of course, are cytokine release syndrome and neurotoxicity. But [these are] very manageable and low grade. So, we have this off-the-shelf option now that's an alternative to CAR T therapy for patients that maybe don't have access to CAR T or don't want to do it and spend that time in the hospital and have all of those long term side effects that we're learning about with CAR T.”

REFERENCE

Adams B. Taking a Bite Out of Myeloma: The Role of Bi-Specific Antibodies in the Treatment of Relapsed/Refractory Multiple Myeloma. Presented at: Hematology/Oncology Pharmacy Association Annual Conference 2024; Tampa, Florida; April 3-6, 2024.