Multiple Myeloma Pipeline Expands With 80+ Therapies as Treatment Paradigms Evolve

The multiple myeloma treatment pipeline has expanded significantly, with over 75 companies developing more than 80 pipeline therapies across clinical and nonclinical stages. Recent clinical trial activity demonstrates the breadth of innovation, with multiple phase 1, 2, and 3 studies initiated in late February 2026 targeting various aspects of the disease.

On February 27, 2026, Kite, A Gilead Company announced a phase 3 study (iMMagine-3) to compare anitocabtagene autoleucel to standard of care therapy in participants with relapsed/refractory multiple myeloma who have received 1 to 3 prior lines of therapy, including an anti-CD38 monoclonal antibody and an immunomodulatory drug. The primary objective of this study is to compare the efficacy of anitocabtagene autoleucel versus standard of care therapy in participants with relapsed/refractory multiple myeloma.

Also on February 27, 2026, AbbVie announced a study to determine the adverse events, change in disease activity, and pharmacokinetics of Etentamig in adult participants with multiple myeloma. The National Cancer Institute conducted a phase 2 Adaptive Study of Subcutaneous Daratumumab, Once Weekly Carfilzomib, and Dexamethasone (DKd) in Patients With High-Risk Smoldering Multiple Myeloma.

On February 25, 2026, Gracell Biotechnologies (Shanghai) Co., Ltd. initiated a phase I/II Clinical Study of Chimeric Antigen Receptor T-cell Therapy Targeting CD19 and BCMA (GC012F) in Patients With Relapsed/Refractory Multiple Myeloma. A leukapheresis procedure will be performed on eligible subjects to manufacture GC012F. Subjects will receive an infusion of GC012F at specified doses after three consecutive days of lymphodepletion consisting of fludarabine and cyclophosphamide. Bridging therapy is allowed between leukapheresis and lymphodepletion.

On February 23, 2026, SCRI Development Innovations LLC conducted a phase II study to evaluate the outpatient administration of Teclistamab or Talquetamab in Multiple Myeloma patients. Teclistamab (TECVAYLI™) is a humanized IgG-4 PAA bispecific antibody designed to target the CD3 receptor complex on T cells and BCMA on B-lineage cells. Pfizer initiated a phase 1B/2 study to determine the Recommended Phase 2 Dose and clinical benefit of elranatamab in combination with other anti-cancer therapies in participants with multiple myeloma.

Leading companies in the space include CASI Pharmaceuticals, Carsgen Therapeutics, Cartesian Therapeutics, Gracell Biotechnology Shanghai Co., Ltd., Sorrento Therapeutics, TeneoOne, Karyopharma Therapeutics, Arcellx, Poseida Therapeutics, Ichnos Sciences, Nerviano Medical Sciences, Bristol Myers Squib, Ascentage Pharma, Ionis Pharmaceuticals, Chongqing Precision Biotech Co., Ltd., CRISPR Therapeutics, AstraZeneca, IGM Biosciences, Novartis, GlaxoSmithKline, Innovent Biologics, Keymed Biociences, Starton Therapeutics, Takeda, Fate Therapeutics, Gilead Sciences, Jiangsu Chia Tai Fenghai Pharmaceutical Co., Ltd., Janssen Pharmaceutical, Nanjing IASO Biotechnology Co., Ltd., GPCR Therapeutics, and Chimerix.

Promising pipeline therapies include TNB-383B, belantamab mafodotin, Pembrolizumab, Melphalan flufenamide (Melflufen), Dexamethasone, Pomalidomide, Venetoclax, Bortezomib, BT062, Selinexor, Lenalidomide, and Methylprednisolone. Zevorcabtagene Autoleucel (Zevor-cel, R&D code: CT053) from Carsgen Therapeutics is among the emerging drug profiles in development.

The CELMoD mezigdomide is showing promise in multiple myeloma, specifically for patients facing treatment resistance. By focusing on the regeneration and activation of the immune system, particularly in cases of T-cell exhaustion, this therapy offers a new path forward. Recent clinical data highlights its effectiveness when paired with other small molecule inhibitors, showing impressive response rates—even in patients where CAR T and bispecific therapies have previously failed.

As the treatment landscape evolves, several key aspects of treatment remain unresolved in the context of current standard of care for newly diagnosed multiple myeloma. The continued role of autologous stem cell transplant (ASCT) and the clinical use of minimal residual disease testing are among the issues being examined. Distinguishing the benefit of quadruplet regimens and transplant and using depth of response to guide treatment are challenges due to limited data, requiring physician judgment in these cases.

The data driving the quadruplet with daratumumab is for transplant-eligible patients and is based on including transplant. There is debate about how long maintenance therapy should continue, with some clinicians recommending treatment until progression, some until MRD negativity, and others for fixed durations of 2 years or 4 years.