Approximately 25% to 35% of new oncology therapies in development are oral medications.
With a variety of multiple myeloma therapies in the pipeline, approximately 25% to 35% of new oncology therapies in development are oral medications.1 Oral oncolytic drugs offer advantages over parenteral treatment, including less invasive administration, patient convenience (eg, location and timing of administration), and prolonged drug exposure.1
Ultimately, these factors are important in improving patients’ quality of life. Evidence demonstrates that pharmacists play a critical role in treating patients on multiple myeloma therapies, especially through a collaborative physician-pharmacist clinic that works to support oral oncolytic medication adherence.2 The multiple myeloma pipeline is continuously expanding, and pharmaceutical companies are involved in research and development for novel oral oncolytic drugs and therapies already approved for other cancer indications.
Multiple Myeloma Drug Pipeline
Venetoclax (Venclexta; AbbVie) is an oral BCL2 inhibitor drug currently FDA approved to treat chronic lymphocytic leukemia (CLL), small lymphocytic leukemia (SLL), and acute myeloid leukemia. Additionally, venetoclax is being studied for the treatment of relapsed and refractory multiple myeloma and has shown promising results in patients positive for the t(11;14) translocation in phase 1/2 clinical studies.3,4
However, the BELLINI phase 3 double-blind randomized trial (NCT02755597) interim results revealed an increased risk of death in patients receiving venetoclax compared with the control group.5 These results prompted the FDA to warn health care professionals of the risks of investigational use of venetoclax for multiple myeloma and to require that no new patients be enrolled in the BELLINI trial and other clinical studies.6 In patients with the t(11;14) translocation, mortality rates were lower, demonstrating that future studies should specifically focus on this patient population.5
In the CANOVA (NCT03539744) phase 3 ongoing study, investigators are evaluating the safety and efficacy of venetoclax plus dexamethasone compared with pomalidomide plus dexamethasone in participants with t(11;14)-positive relapsed or refractory multiple myeloma.7
APG-2575 (lisaftoclax; Ascentage Pharma) is a novel oral BCL2 inhibitor being studied for several hematologic cancers including multiple myeloma.8 Additionally, the FDA has granted Orphan Drug Designation to lisaftoclax for the treatment of multiple myeloma.8 Lisaftoclax is being investigated in an ongoing phase 1b/2 clinical trial (NCT04942067) in combination with other therapies in patients with relapsed or refractory multiple myeloma.9
Ibrutinib (Imbruvica; Pharmacyclics and Janssen) is a novel first-in-class once-daily Bruton tyrosine kinase inhibitor that is FDA approved for CLL/SLL, Waldenström macroglobulinemia, chronic graft-vs-host disease, mantle cell lymphoma, and marginal zone lymphoma.10
Additionally, the safety and efficacy of ibrutinib were evaluated in a phase 1/2b study (NCT01962792) combined with carfilzomib/dexamethasone in patients with relapsed/refractory multiple myeloma.11 The study revealed that patients had an overall response rate of 71%, median progression-free survival of 7.4 months, and a median overall survival of 35.9 months.11 The most common grade 3 or greater hematologic treatment-emergent adverse events were anemia and thrombocytopenia.11
Myeloma-Developing Regimens Using Genomics (MyDRUG)
The MyDRUG phase 1/2 study (NCT03732703) is an ongoing precision medicine clinical trial that aims to develop new multiple myeloma regimens based on individual patients’ genomics.12 Findings from the Multiple Myeloma Research Foundation CoMMpass study (NCT01454297) and the Multiple Myeloma Research Consortium Molecular Profiling Initiative revealed that genetic mutations can play a role in the disease, prompting the MyDRUG trial.13,14
Additionally, this study includes high-risk multiple myeloma patients with 1 to 3 prior lines of therapy.12,13 During this trial, investigators assign patients to the appropriate therapy based on their pharmacogenomic profile along with a standard-of-care regimen that includes ixazomib, pomalidomide, and dexamethasone.12
In this study, the oral oncolytic treatment options include investigational drugs and those approved for other cancers that have shown promise for multiple myeloma, such as abemaciclib (cyclin-dependent kinase mutations), enasidenib (isocitrate dehydrogenase mutations), cobimetinib (RAF/RAS mutations), and venetoclax (chromosomal translocation t[11;14]).13,14
Furthermore, investigators in the MyDRUG trial plan to enroll 228 patients into one of 8 treatment arms.12 Patients with a greater than 25% mutation to any of the genes being studied are eligible to be enrolled in one of these treatment arms.12 Because the study enables multiple therapies to be evaluated at once, this has the potential to expand treatment to high-risk multiple myeloma patients.